-
Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial Lancet (IF 168.9) Pub Date : 2024-02-05 Yuanyuan Wang PhD, Prof Rong Li MD, Rui Yang MD, Danni Zheng PhD, Lin Zeng PhD, Ying Lian MSc, Prof Yimin Zhu MD, Prof Junli Zhao MD, Prof Xiaoyan Liang MD, Prof Wen Li MD, Prof Jianqiao Liu MD, Prof Li Tang MD, Prof Yunxia Cao MD, Prof Guimin Hao MD, Prof Huichun Wang MD, Hua Zhang PhD, Rui Wang PhD, Prof Ben W Mol PhD, Prof Hefeng Huang MD, Prof Jie Qiao MD
Introduced in 1992, intracytoplasmic sperm injection (ICSI) was initially indicated for severe male infertility; however, its use has since been expanded to non-severe male infertility. We aimed to compare the efficacy and safety of ICSI versus conventional in-vitro fertilisation (IVF) in couples with infertility with non-severe male factor. We conducted an investigator-initiated, multicentre, open-label
-
Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial Lancet (IF 168.9) Pub Date : 2024-02-01 Mehreen S Datoo DPhil, Alassane Dicko PhD, Halidou Tinto PhD, Jean-Bosco Ouédraogo MD, Mainga Hamaluba MD, Ally Olotu DPhil, Emma Beaumont MSc, Fernando Ramos Lopez MSc, Hamtandi Magloire Natama PhD, Sophie Weston MSc, Mwajuma Chemba MSc, Yves Daniel Compaore MD, Djibrilla Issiaka PhD, Diallo Salou PhD, Athanase M Some MD, Sharon Omenda MBChB, Alison Lawrie PhD, Philip Bejon PhD, Harish Rao PhD, Prof
Recently, we found that a new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina Faso. Here, we report on safety and efficacy of the vaccine in a phase 3 trial enrolling over 4800 children across four countries followed for up to 18 months at seasonal sites and 12 months at standard sites. We did a double-blind,
-
Effectiveness of a comprehensive package based on electronic medication monitors at improving treatment outcomes among tuberculosis patients in Tibet: a multicentre randomised controlled trial Lancet (IF 168.9) Pub Date : 2024-01-31 Prof Xiaolin Wei PhD, Joseph Paul Hicks PhD, Zhitong Zhang MPH, Victoria Haldane PhD, Pande Pasang MD, Linhua Li MD, Tingting Yin MPH, Bei Zhang MPH, Yinlong Li PhD, Qiuyu Pan PhD, Xiaoqiu Liu PhD, Prof John Walley FFPH, Prof Jun Hu PhD
WHO recommends that electronic medication monitors, a form of digital adherence technology, be used as a complement to directly observed treatment (DOT) for tuberculosis, as DOT is inconvenient and costly. However, existing evidence about the effectiveness of these monitors is inconclusive. Therefore, we evaluated the effectiveness of a comprehensive package based on electronic medication monitors
-
Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children Lancet (IF 168.9) Pub Date : 2024-01-25 Priyanka D Patel MBBS, Yuanyuan Liang PhD, James E Meiring PhD, Nedson Chasweka BSc, Pratiksha Patel MBBS, Theresa Misiri MPH, Felistas Mwakiseghile MSc, Richard Wachepa BSc, Happy C Banda BSc, Florence Shumba PGD, Gift Kawalazira MBBS, Queen Dube PhD, Nginache Nampota-Nkomba MBBS, Osward M Nyirenda BSc, Tsion Girmay MPH, Shrimati Datta PhD, Leslie P Jamka MEM, J Kathleen Tracy PhD, Matthew B Laurens
Randomised controlled trials of typhoid conjugate vaccines among children in Africa and Asia have shown high short-term efficacy. Data on the durability of protection beyond 2 years are sparse. We present the final analysis of a randomised controlled trial in Malawi, encompassing more than 4 years of follow-up, with the aim of investigating vaccine efficacy over time and by age group. In this phase
-
AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial Lancet (IF 168.9) Pub Date : 2024-01-24 Jun Lv MMed, Hui Wang MD, Xiaoting Cheng MD, Yuxin Chen PhD, Daqi Wang PhD, Longlong Zhang MMed, Qi Cao BMed, Honghai Tang PhD, Shaowei Hu PhD, Kaiyu Gao PhD, Mengzhao Xun BMed, Jinghan Wang MD, Zijing Wang BMed, Biyun Zhu PhD, Chong Cui BMed, Ziwen Gao PhD, Luo Guo PhD, Sha Yu MD, Luoying Jiang BMed, Yanbo Yin MMed, Jiajia Zhang MMed, Prof Bing Chen MD, Prof Wuqing Wang MD, Prof Renjie Chai DPhil
Autosomal recessive deafness 9, caused by mutations of the gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human transgene (AAV1-hOTOF) as a
-
Evaluating the efficacy and safety of pozelimab in patients with CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy disease: an open-label phase 2 and 3 study Lancet (IF 168.9) Pub Date : 2024-01-23 Prof Ahmet Ozen MD, Voranush Chongsrisawat MD, Asena Pinar Sefer MD, Burcu Kolukisa MD, Jessica J Jalbert PhD, Karoline A Meagher PhD, Taylor Brackin MS, Hagit Baris Feldman MD, Prof Safa Baris MD, Prof Elif Karakoc-Aydiner MD, Rabia Ergelen MD, Prof Ivan J Fuss MD, Heather Moorman MSPH, Narissara Suratannon MD, Prof Kanya Suphapeetiporn MD, Lorah Perlee PhD, Olivier A Harari MB BChir, George D Yancopoulos
CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) is an ultra-rare genetic disorder characterised by intestinal lymphatic damage, lymphangiectasia, and protein-losing enteropathy caused by overactivation of the complement system. We assessed the efficacy and safety of pozelimab, an antibody blocking complement component 5. This open-label
-
The effect of computerised decision support alerts tailored to intensive care on the administration of high-risk drug combinations, and their monitoring: a cluster randomised stepped-wedge trial Lancet (IF 168.9) Pub Date : 2024-01-20 Tinka Bakker PhD, Joanna E Klopotowska PhD, Dave A Dongelmans MD, Saeid Eslami PhD, Wytze J Vermeijden MD, Stefaan Hendriks MD, Julia ten Cate MD, Attila Karakus MD, Ilse M Purmer MD, Sjoerd H W van Bree MD, Peter E Spronk MD, Martijn Hoeksema MD, Prof Evert de Jonge MD, Prof Nicolette F de Keizer PhD, Prof Ameen Abu-Hanna PhD, SIMPLIFY study group, Dorieke E.M. van Balen, Peter F. Schutte, Marnix
Drug–drug interactions (DDIs) can harm patients admitted to the intensive care unit (ICU). Yet, clinical decision support systems (CDSSs) aimed at helping physicians prevent DDIs are plagued by low-yield alerts, causing alert fatigue and compromising patient safety. The aim of this multicentre study was to evaluate the effect of tailoring potential DDI alerts to the ICU setting on the frequency of
-
Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study Lancet (IF 168.9) Pub Date : 2024-01-18 Prof Jeffrey S Weber MD PhD, Matteo S Carlino PhD, Adnan Khattak MD, Tarek Meniawy PhD, George Ansstas MD, Matthew H Taylor MD, Kevin B Kim MD, Meredith McKean MD, Prof Georgina V Long MD PhD, Ryan J Sullivan MD, Mark Faries MD, Thuy T Tran MD, C Lance Cowey MD, Andrew Pecora MD, Montaser Shaheen MD, Jennifer Segar MD, Theresa Medina MD, Victoria Atkinson MD, Geoffrey T Gibney MD, Jason J Luke MD,
Checkpoint inhibitors are standard adjuvant treatment for stage IIB–IV resected melanoma, but many patients recur. Our study aimed to evaluate whether mRNA-4157 (V940), a novel mRNA-based individualised neoantigen therapy, combined with pembrolizumab, improved recurrence-free survival and distant metastasis-free survival versus pembrolizumab monotherapy in resected high-risk melanoma. We did an open-label
-
Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales Lancet (IF 168.9) Pub Date : 2024-01-15 The HDR UK COALESCE Consortium, Steven Kerr PhD, Stuart Bedston PhD, Genevieve Cezard PhD, Alexia Sampri PhD, Siobhan Murphy PhD, Declan T Bradley PhD, Kirsty Morrison PhD, Ashley Akbari MSc, William Whiteley PhD, Christopher Sullivan PhD, Lynsey Patterson PhD, Prof Kamlesh Khunti PhD, Prof Spiros Denaxas PhD, Thomas Bolton PhD, Samaira Khan BA, Alan Keys FBCS, David Weatherill MEng, Karen Mooney BA
Background Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes—ie, COVID-19 hospitalisation or death—compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of
-
Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin–piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial Lancet (IF 168.9) Pub Date : 2024-01-12 Hellen C Barsosio MD, Mwayiwawo Madanitsa PhD, Everlyne D Ondieki MPH, James Dodd MSc, Eric D Onyango MSc, Kephas Otieno MSc, Prof Duolao Wang PhD, Jenny Hill PhD, Prof Victor Mwapasa PhD, Prof Kamija S Phiri PhD, Prof Kenneth Maleta PhD, Prof Miriam Taegtmeyer PhD, Simon Kariuki PhD, Christentze Schmiegelow PhD, Julie R Gutman MD, Prof Feiko O ter Kuile PhD
The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of to the antifolate sulfadoxine–pyrimethamine. We assessed whether addition of monthly dihydroartemisinin–piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant
-
Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial Lancet (IF 168.9) Pub Date : 2024-01-11 Prof B Joseph Elmunzer MD, Lydia D Foster MS, Prof Jose Serrano MD PhD, Prof Gregory A Coté MD, Prof Steven A Edmundowicz MD, Prof Sachin Wani MD, Prof Raj Shah MD, Ji Young Bang MD, Prof Shyam Varadarajulu MD, Prof Vikesh K Singh MD, Prof Mouen Khashab MD, Prof Richard S Kwon MD, Prof James M Scheiman MD, Prof Field F Willingham MD, Prof Steven A Keilin MD, Prof Georgios I Papachristou MD PhD, Prof
The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially
-
Term planned delivery based on fetal growth assessment with or without the cerebroplacental ratio in low-risk pregnancies (RATIO37): an international, multicentre, open-label, randomised controlled trial Lancet (IF 168.9) Pub Date : 2024-01-11 Marta Rial-Crestelo PhD, Prof Marek Lubusky PhD, Prof Mauro Parra-Cordero PhD, Prof Ladislav Krofta PhD, Prof Anna Kajdy PhD, Eyal Zohav MD, Elena Ferriols-Perez PhD, Prof Rogelio Cruz-Martinez PhD, Prof Marian Kacerovsky PhD, Elena Scazzocchio PhD, Lucie Roubalova MD, Pamela Socias MD, Lubomir Hašlík PhD, Jan Modzelewski PhD, Eran Ashwal MD, Julia Castellá-Cesari MD, Prof Monica Cruz-Lemini PhD, Prof
The cerebroplacental ratio is associated with perinatal mortality and morbidity, but it is unknown whether routine measurement improves pregnancy outcomes. We aimed to evaluate whether the addition of cerebroplacental ratio measurement to the standard ultrasound growth assessment near term reduces perinatal mortality and severe neonatal morbidity, compared with growth assessment alone. RATIO37 was
-
Efficacy and safety of aldosterone synthase inhibition with and without empagliflozin for chronic kidney disease: a randomised, controlled, phase 2 trial Lancet (IF 168.9) Pub Date : 2023-12-15 Katherine R Tuttle MD, Sibylle J Hauske MD, Maria Eugenia Canziani MD, Maria Luiza Caramori MD, David Cherney PhD, Lisa Cronin MD, Hiddo J L Heerspink PhD, Christian Hugo MD, Masaomi Nangaku PhD, Ricardo Correa Rotter MD, Arnold Silva MD, Shimoli V Shah MD, Zhichao Sun PhD, Dorothea Urbach MD, Dick de Zeeuw MD, Peter Rossing MD, ASi in CKD group, Katherine R Tuttle, Sibylle J Hauske, Maria Eugenia
Excess aldosterone accelerates chronic kidney disease progression. This phase 2 clinical trial assessed BI 690517, an aldosterone synthase inhibitor, for efficacy, safety, and dose selection. This was a multinational, randomised, controlled, phase 2 trial. People aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 30 to less than 90 mL/min/1·73 m, a urine albumin to creatinine
-
Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline–trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial Lancet (IF 168.9) Pub Date : 2023-12-14 Inder Kaul MD, Sharon Sawchak RN, Prof Christoph U Correll MD, Rishi Kakar MD, Prof Alan Breier MD, Haiyuan Zhu PhD, Andrew C Miller PhD, Steven M Paul MD, Stephen K Brannan MD
New treatments with new mechanisms are urgently needed for people with schizophrenia. Xanomeline is a dual M and M-preferring muscarinic receptor agonist that does not block D dopamine receptors, unlike all currently approved treatments for schizophrenia. Xanomeline–trospium (KarXT) combines xanomeline with the peripherally restricted muscarinic receptor antagonist trospium chloride with the goal of
-
Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study Lancet (IF 168.9) Pub Date : 2023-12-14 Chiaojung Jillian Tsai MD PhD, Jonathan T Yang MD PhD, Narek Shaverdian MD, Juber Patel MS, Annemarie F Shepherd MD, Juliana Eng MD, David Guttmann MD, Randy Yeh MD, Prof Daphna Y Gelblum MD, Azadeh Namakydoust MD, Isabel Preeshagul DO, Prof Shanu Modi MD, Prof Andrew Seidman MD, Prof Tiffany Traina MD, Prof Pamela Drullinsky MD, Jessica Flynn MS, Prof Zhigang Zhang PhD, Andreas Rimner MD, Erin F Gillespie
Most patients with metastatic cancer eventually develop resistance to systemic therapy, with some having limited disease progression (ie, oligoprogression). We aimed to assess whether stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve patient outcomes. We did a phase 2, open-label, randomised controlled trial of SBRT in patients with oligoprogressive metastatic breast
-
Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study Lancet (IF 168.9) Pub Date : 2023-12-12 European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration, Kanika Inamdar Dharmayat, Antonio J. Vallejo-Vaz, Christophe A.T. Stevens, Julia M. Brandts, Alexander R.M. Lyons, Urh Groselj, Marianne Abifadel, Carlos A. Aguilar-Salinas, Khalid Alhabib, Mutaz Alkhnifsawi, Wael Almahmeed, Fahad Alnouri, Rodrigo Alonso, Khalid Al-Rasadi, Tester F. Ashavaid, Maciej Banach, Sophie
Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand
-
Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial Lancet (IF 168.9) Pub Date : 2023-12-11 Prof Nils Chaillet PhD, Prof Benoît Mâsse PhD, Prof William A Grobman MD, Prof Allison Shorten PhD, Prof Robert Gauthier MD, Prof Patrick Rozenberg MD, Marylène Dugas PhD, Prof Jean-Charles Pasquier MD, Prof François Audibert MD, Prof Haim A Abenhaim MD, Suzanne Demers MD, Prof Bruno Piedboeuf MD, Prof William D Fraser MD, Prof Robert Gagnon MD, Guy-Paul Gagné MD, Prof Diane Francoeur MD, Prof Isabelle
Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal
-
Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL): a randomised, multicentre, open-label, phase 4 study Lancet (IF 168.9) Pub Date : 2023-12-07 Prof David J Jackson PhD, Prof Liam G Heaney MD, Prof Marc Humbert MD, Brian D Kent MD, Anat Shavit DVM, Lina Hiljemark BPharm, Lynda Olinger MSc, David Cohen PhD, Andrew Menzies-Gow PhD, Stephanie Korn MD, SHAMAL Investigators, Claus Kroegel, Cristiano Caruso, Ilaria Baglivo, Stefania Colantuono, David Jackson, Dirk Skowasch, Fabiano Di Marco, Francis Couturaud, Frank Käßner, Iwona Cwiek, Markus Teber
Stepwise intensification of inhaled corticosteroids (ICS) is routine for severe eosinophilic asthma, despite some poor responses to high-dose ICS. Dose reductions are recommended in patients responding to biologics, but little supporting safety evidence exists. SHAMAL was a phase 4, randomised, open-label, active-controlled study done at 22 study sites in four countries. Eligible participants were
-
Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study Lancet (IF 168.9) Pub Date : 2023-12-05 Prof Gregory Bruce Mann MBBS, Anita Rohini Skandarajah MBBS, Nicholas Zdenkowski MBBS, Janemary Hughes BSc, Allan Park MN, Prof Dennis Petrie PhD, Karinna Saxby PhD, Prof Sean M Grimmond PhD, Anand Murugasu MBBS, Prof Andrew J Spillane MBBS, Prof Boon H Chua MBBS, Heath Badger BSc, Helen Braggett MPH, Prof Val Gebski MStat, Arlene Mou MBBS, John P Collins MBBS, Allison K Rose MBBS
Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy. PROSPECT is a prospective
-
Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial Lancet (IF 168.9) Pub Date : 2023-12-01 Prof Mark J Peters PhD, Doug W Gould PhD, Samiran Ray PhD, Karen Thomas MSc, Irene Chang MSc, Marzena Orzol MSc, Lauran O'Neill BSc, Rachel Agbeko PhD, Carly Au BSc, Prof Elizabeth Draper PhD, Prof Lee Elliot-Major PhD, Elisa Giallongo MSc, Gareth A L Jones MD, Lamprini Lampro MSc, Jon Lillie MD, Jon Pappachan MD, Sam Peters BSc, Padmanabhan Ramnarayan MD, Zia Sadique PhD, Prof Kathryn M Rowan PhD
The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care. Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial
-
Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-12-01 Prof Uwe Platzbecker MD, Valeria Santini MD, Prof Pierre Fenaux MD, Prof Mikkael A Sekeres MD, Prof Michael R Savona MD, Yazan F Madanat MD, Maria Díez-Campelo MD, David Valcárcel MD, Thomas Illmer MD, Anna Jonášová MD, Prof Petra Bělohlávková PhD, Laurie J Sherman BSN, Tymara Berry MD, Souria Dougherty MBA, Sheetal Shah BS, Qi Xia PhD, Libo Sun PhD, Ying Wan PhD, Fei Huang PhD, Annat Ikin PhD, Shyamala
Unmet medical needs remain in patients with red blood cell transfusion-dependent (RBC-TD) lower-risk myelodysplastic syndromes (LR-MDS) who are not responding to or are ineligible for erythropoiesis-stimulating agents (ESAs). Imetelstat, a competitive telomerase inhibitor, showed promising results in a phase 2 trial. We aimed to compare the RBC transfusion independence (RBC-TI) rate with imetelstat
-
Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-12-01 Prof Ana Oaknin MD, Laurence Gladieff MD, Jerónimo Martínez-García, Guillermo Villacampa MSc, Munetaka Takekuma MD, Ugo De Giorgi MD, Prof Kristina Lindemann MD, Linn Woelber MD, Prof Nicoletta Colombo MD, Prof Linda Duska MD, Alexandra Leary MD, Ana Godoy-Ortiz MD, Shin Nishio MD, Antoine Angelergues MD, Maria Jesús Rubio MD, Lorena Fariñas-Madrid MD, Satoshi Yamaguchi MD, Prof Domenica Lorusso MD
The GOG240 trial established bevacizumab with chemotherapy as standard first-line therapy for metastatic or recurrent cervical cancer. In the BEATcc trial (ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030), we aimed to evaluate the addition of an immune checkpoint inhibitor to this standard backbone. In this investigator-initiated, randomised, open-label, phase 3 trial, patients from 92 sites in Europe, Japan
-
Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials Lancet (IF 168.9) Pub Date : 2023-11-23 Marcus Maurer MD, Luis Felipe Ensina PhD, Ana Maria Gimenez-Arnau MD, Gordon Sussman MD, Michihiro Hide MD, Sarbjit Saini MD, Clive Grattan MD, Daria Fomina MD, Dimitrios Rigopoulos MD, Frederic Berard MD, Giorgio Walter Canonica MD, Heike Rockmann MD, Carla Irani MD, Jacek C Szepietowski PhD, Jeffrey Leflein MD, Jonathan A Bernstein MD, Jonny G Peter MD PhD, Kanokvalai Kulthanan MD, Kiran Godse MD
Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies. PEARL-1 and PEARL-2 were identically designed
-
Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-11-15 Kamala Thriemer PhD, Tamiru Shibiru Degaga MD, Michael Christian MD, Mohammad Shafiul Alam PhD, Megha Rajasekhar PhD, Benedikt Ley PhD, Mohammad Sharif Hossain MSc, Mohammad Golam Kibria MSc, Tedla Teferi Tego MSc, Dagamawie Tadesse Abate MSc, Sophie Weston MPH, Hellen Mnjala MSc, Angela Rumaseb MSc, Ari Winasti Satyagraha PhD, Arkasha Sadhewa MSc, Lydia Vista Panggalo MSc, Lenny L Ekawati MPH, Grant
In areas co-endemic for and there is an increased risk of parasitaemia following malaria. Radical cure is currently only recommended for patients presenting with malaria. Expanding the indication for radical cure to patients presenting with malaria could reduce their risk of subsequent parasitaemia. We did a multicentre, open-label, superiority randomised controlled trial in five health clinics in
-
Ubrogepant for the treatment of migraine attacks during the prodrome: a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA Lancet (IF 168.9) Pub Date : 2023-11-15 Prof David W Dodick MD, Prof Peter J Goadsby MD, Prof Todd J Schwedt MD, Prof Richard B Lipton MD, Chengcheng Liu PhD, Kaifeng Lu PhD, Sung Yun Yu BA, Lawrence Severt MD, Michelle Finnegan MPH, Joel M Trugman MD
Ubrogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist that is approved for acute treatment of migraine. The prodrome is the earliest phase of a migraine attack and is characterised by non-aura symptoms that precede headache onset. The aim of this trial was to evaluate the efficacy, safety, and tolerability of ubrogepant 100 mg compared with placebo for the acute treatment of migraine
-
Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth: a systematic review and individual participant data meta-analysis Lancet (IF 168.9) Pub Date : 2023-11-14 Anna Lene Seidler PhD, Mason Aberoumand MAppStat, Kylie E Hunter MPH, Angie Barba MSciMed, Sol Libesman PhD, Jonathan G Williams PhD, Nipun Shrestha PhD, Jannik Aagerup MPH, James X Sotiropoulos MD, Prof Alan A Montgomery PhD, Prof Gillian M L Gyte MPhil, Prof Lelia Duley MD, Prof Lisa M Askie PhD, iCOMP Collaborators, Anna Lene Seidler, Mason Aberoumand, Kylie E Hunter, Angie Barba, Sol Libesman,
Umbilical cord clamping strategies at preterm birth have the potential to affect important health outcomes. The aim of this study was to compare the effectiveness of deferred cord clamping, umbilical cord milking, and immediate cord clamping in reducing neonatal mortality and morbidity at preterm birth. We conducted a systematic review and individual participant data meta-analysis. We searched medical
-
Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study Lancet (IF 168.9) Pub Date : 2023-11-14 Emmanuel Messas MD PhD, Alexander Ijsselmuiden MD, Danijela Trifunović-Zamaklar MD, Bernard Cholley MD, Etienne Puymirat MD, Jonathan Halim MD, Radmila Karan MD, Menno van Gameren MD, Duško Terzić MD, Vladimir Milićević MD, Mickael Tanter PhD, Mathieu Pernot PhD, Guillaume Goudot MD
Calcific aortic stenosis is commonly treated using surgical or transcatheter aortic valve replacement; however, many patients are not considered suitable candidates for these interventions due to severe comorbidities and limited life expectancy. As such, non-invasive therapies might offer alternative therapeutic possibilities in these patients. This study aimed to assess the safety of non-invasive
-
Short, medium, and long deferral of umbilical cord clamping compared with umbilical cord milking and immediate clamping at preterm birth: a systematic review and network meta-analysis with individual participant data Lancet (IF 168.9) Pub Date : 2023-11-14 Anna Lene Seidler PhD, Sol Libesman PhD, Kylie E Hunter MPH, Angie Barba MSciMed, Mason Aberoumand MAppStat, Jonathan G Williams PhD, Nipun Shrestha PhD, Jannik Aagerup MPH, James X Sotiropoulos MD, Prof Alan A Montgomery PhD, Gillian M L Gyte MPhil, Prof Lelia Duley MD, Prof Lisa M Askie PhD, iCOMP Collaborators, Anna Lene Seidler, Sol Libesman, Kylie E Hunter, Angie Barba, Mason Aberoumand, Jonathan
Deferred (also known as delayed) cord clamping can improve survival of infants born preterm (before 37 weeks of gestation), but the optimal duration of deferral remains unclear. We conducted a systematic review and individual participant data network meta-analysis with the aim of comparing the effectiveness of umbilical cord clamping strategies with different timings of clamping or with cord milking
-
Impact of discontinuing oxytocin in active labour on neonatal morbidity: an open-label, multicentre, randomised trial Lancet (IF 168.9) Pub Date : 2023-11-09 Aude Girault PhD, Prof Loïc Sentilhes PhD, Raoul Desbrière PhD, Prof Paul Berveiller PhD, Diane Korb PhD, Charline Bertholdt MD, Julie Carrara MD, Prof Norbert Winer PhD, Prof Eric Verspyck PhD, Eric Boudier MD, Prof Tiphaine Barjat PhD, Gilles Levy MD, Georges Emmanuel Roth RM, Prof Gilles Kayem PhD, Mona Massoud PhD, Caroline Bohec PhD, Prof Paul Guerby PhD, Prof Elie Azria PhD, Prof Julie Blanc
Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labour. We aimed to assess the impact of discontinuing oxytocin during active labour on neonatal morbidity. STOPOXY was a multicentre, randomised, open-label, controlled, superiority trial conducted in 21 maternity units
-
Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-11-03 Quincy Chu MD, Francesco Perrone MD, Prof Laurent Greillier MD, Wei Tu PhD, Maria Carmela Piccirillo MD, Federica Grosso MD, Giuseppe Lo Russo MD, Marie Florescu MD, Manlio Mencoboni MD, Alessandro Morabito MD, Fabiana Letizia Cecere MD, Giovanni Luca Ceresoli MD, David E Dawe MD, Paolo Andrea Zucali MD, Maria Pagano MD, John R Goffin MD, Myriam Locatelli Sanchez MD, Cesare Gridelli MD, Prof Gerard
Pleural mesothelioma usually presents at an advanced, incurable stage. Chemotherapy with platinum–pemetrexed is a standard treatment. We hypothesised that the addition of pembrolizumab to platinum–pemetrexed would improve overall survival in patients with pleural mesothelioma. We did this open-label, international, randomised phase 3 trial at 51 hospitals in Canada, Italy, and France. Eligible participants
-
Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials Lancet (IF 168.9) Pub Date : 2023-11-03 Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Carolyn Taylor, David Dodwell, Paul McGale, Robert K Hills, Richard Berry, Rosie Bradley, Jeremy Braybrooke, Mike Clarke, Richard Gray, Francesca Holt, Zulian Liu, Hongchao Pan, Richard Peto, Ewan Straiton, Charlotte Coles, Fran Duane, Christophe Hennequin, Glenn Jones, Thorsten Kühn, Sileida Oliveros, Jens Overgaard, Kathy I Pritchard, Chang-Ok
Background Radiotherapy has become much better targeted since the 1980s, improving both safety and efficacy. In breast cancer, radiotherapy to regional lymph nodes aims to reduce risks of recurrence and death. Its effects have been studied in randomised trials, some before the 1980s and some after. We aimed to assess the effects of regional node radiotherapy in these two eras. Methods In this meta-analysis
-
Zibotentan in combination with dapagliflozin compared with dapagliflozin in patients with chronic kidney disease (ZENITH-CKD): a multicentre, randomised, active-controlled, phase 2b, clinical trial Lancet (IF 168.9) Pub Date : 2023-11-03 Prof Hiddo J L Heerspink PhD, Arihiro Kiyosue PhD, Prof David C Wheeler MD, Min Lin PhD, Emma Wijkmark MSc, Glenn Carlson MD, Anne-Kristina Mercier PhD, Magnus Åstrand PhD, Sebastian Ueckert PhD, Peter J Greasley PhD, Phil Ambery MBChB
In patients with chronic kidney disease, SGLT2 inhibitors and endothelin A receptor antagonists (ERAs) can reduce albuminuria and glomerular filtration rate (GFR) decline. We assessed the albuminuria-lowering efficacy and safety of the ERA zibotentan combined with the SGLT2 inhibitor dapagliflozin. ZENITH-CKD was a multicentre, randomised, double-blind, active-controlled clinical trial, done in 170
-
Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-11-03 Prof Brad H Rovin MD, Prof Jonathan Barratt PhD, Prof Hiddo J L Heerspink PhD, Prof Charles E Alpers MD, Stewart Bieler BA, Dong-Wan Chae PhD, Ulysses A Diva PhD, Prof Jürgen Floege MD, Prof Loreto Gesualdo MD, Jula K Inrig MD, Donald E Kohan MD, Radko Komers MD, Laura Ann Kooienga MD, Prof Richard Lafayette MD, Bart Maes MD, Robert Małecki MD, Alex Mercer PhD, Prof Irene L Noronha MD, Prof Se Won
Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks
-
Long-term outcomes with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in ST-segment elevation myocardial infarction: 5-year follow-up of the BIOSTEMI randomised superiority trial Lancet (IF 168.9) Pub Date : 2023-10-25 Juan F Iglesias MD, Marco Roffi MD, Sylvain Losdat PhD, Prof Olivier Muller MD, Sophie Degrauwe MD, David J Kurz MD, Laurent Haegeli MD, Daniel Weilenmann MD, Christoph Kaiser MD, Maxime Tapponnier MD, Stéphane Cook MD, Florim Cuculi MD, Dik Heg PhD, Prof Stephan Windecker MD, Thomas Pilgrim MD
Biodegradable polymer sirolimus-eluting stents improve early stent-related clinical outcomes compared to durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The long-term advantages of biodegradable polymer sirolimus-eluting stents after complete degradation of its polymer coating in patients
-
Mortality in randomised controlled trials using paclitaxel-coated devices for femoropopliteal interventional procedures: an updated patient-level meta-analysis Lancet (IF 168.9) Pub Date : 2023-10-24 Sahil A Parikh MD, Prof Peter A Schneider MD, Christopher M Mullin MS, Tyson Rogers MS, Prof William A Gray MD
Numerous randomised clinical trials and real-world studies have supported the safety of paclitaxel-coated devices for the treatment of femoropopliteal occlusive disease. However, a 2018 summary-level meta-analysis suggested an increased mortality risk for paclitaxel-coated devices compared with uncoated control devices. This study presents an updated analysis of deaths using the most complete and current
-
Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-10-20 Shukui Qin MD, Minshan Chen MD, Ann-Lii Cheng MD, Ahmed O Kaseb MD, Prof Masatoshi Kudo MD, Han Chu Lee MD, Adam C Yopp MD, Prof Jian Zhou MD, Prof Lu Wang MD, Prof Xiaoyu Wen MD, Prof Jeong Heo MD, Prof Won Young Tak MD, Shinichiro Nakamura MD, Kazushi Numata MD, Thomas Uguen MD, David Hsiehchen MD, Edward Cha MD, Stephen P Hack MBChB, Qinshu Lian PhD, Ning Ma MD, Jessica H Spahn PhD, Prof Yulei Wang
No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma. In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk
-
Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial Lancet (IF 168.9) Pub Date : 2023-10-20 Yelena Y Janjigian MD, Akihito Kawazoe MD, Yuxian Bai MD, Jianming Xu MD, Sara Lonardi MD, Prof Jean Phillipe Metges MD, Patricio Yanez MD, Prof Lucjan S Wyrwicz MD, Lin Shen MD, Yuriy Ostapenko MD, Prof Mehmet Bilici MD, Prof Hyun Cheol Chung MD, Kohei Shitara MD, Shu-Kui Qin MD, Prof Eric Van Cutsem MD, Prof Josep Tabernero MD, Kan Li PhD, Chie-Schin Shih MD, Pooja Bhagia MD, Prof Sun Young Rha MD
Evidence for the efficacy of combined PD-1 and HER2 blockade with chemotherapy on progression-free and overall survival in HER2-positive gastro-oesophageal cancer is scarce. The first interim analysis of the randomised, phase 3 KEYNOTE-811 study showed a superior objective response with pembrolizumab compared with placebo when added to trastuzumab plus fluoropyrimidine and platinum-based chemotherapy
-
Gestational weight change in a diverse pregnancy cohort and mortality over 50 years: a prospective observational cohort study Lancet (IF 168.9) Pub Date : 2023-10-19 Stefanie N Hinkle PhD, Prof Sunni L Mumford PhD, Prof Katherine L Grantz MD, Prof Pauline Mendola PhD, Prof James L Mills MD, Prof Edwina H Yeung PhD, Anna Z Pollack PhD, Sonia M Grandi PhD, Prof Rajeshwari Sundaram PhD, Yan Qiao MPH, Prof Enrique F Schisterman PhD, Prof Cuilin Zhang PhD
High weight gain in pregnancy is associated with greater postpartum weight retention, yet long-term implications remain unknown. We aimed to assess whether gestational weight change was associated with mortality more than 50 years later. The Collaborative Perinatal Project (CPP) was a prospective US pregnancy cohort (1959–65). The CPP Mortality Linkage Study linked CPP participants to the National
-
Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials Lancet (IF 168.9) Pub Date : 2023-10-19 Jeffrey S Heier MD, Eleonora M Lad MD, Prof Frank G Holz MD, Prof Philip J Rosenfeld MD, Prof Robyn H Guymer MBBS, David Boyer MD, Federico Grossi MD, Prof Caroline R Baumal MD, Prof Jean-Francois Korobelnik MD, Prof Jason S Slakter MD, Nadia K Waheed MD, Ravi Metlapally PhD, Prof Ian Pearce MBChB, Nathan Steinle MD, Anibal A Francone MD, Allen Hu MD, David R Lally MD, Pascal Deschatelets PhD, Cedric
Geographic atrophy is a leading cause of progressive, irreversible vision loss. The objectives of OAKS and DERBY were to assess the efficacy and safety of pegcetacoplan compared with sham treatment in patients with geographic atrophy. OAKS and DERBY were two 24-month, multicentre, randomised, double-masked, sham-controlled, phase 3 studies, in which patients aged 60 years and older with geographic
-
Once-weekly insulin icodec versus once-daily insulin degludec as part of a basal-bolus regimen in individuals with type 1 diabetes (ONWARDS 6): a phase 3a, randomised, open-label, treat-to-target trial Lancet (IF 168.9) Pub Date : 2023-10-17 Prof David Russell-Jones MD, Prof Tetsuya Babazono MD, Roman Cailleteau MD, Susanne Engberg MD, Prof Concetta Irace MD, Maiken Ina Siegismund Kjaersgaard PhD, Prof Chantal Mathieu MD, Julio Rosenstock MD, Vincent Woo MD, David C Klonoff MD
ONWARDS 6 compared the efficacy and safety of once-weekly subcutaneous insulin icodec (icodec) and once-daily insulin degludec (degludec) in adults with type 1 diabetes. This 52-week (26-week main phase plus a 26-week safety extension), randomised, open-label, treat-to-target, phase 3a trial was done at 99 sites across 12 countries. Adults with type 1 diabetes (glycated haemoglobin [HbA] <10·0% [86
-
Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-10-16 Prof Alexander C Ford MD, Alexandra Wright-Hughes MSc, Sarah L Alderson, Pei-Loo Ow MSc, Prof Matthew J Ridd PhD, Prof Robbie Foy PhD, Gina Bianco, Prof Felicity L Bishop PhD, Matthew Chaddock BA, Heather Cook PhD, Deborah Cooper, Catherine Fernandez PhD, Prof Elspeth A Guthrie MD, Suzanne Hartley MSc, Amy Herbert MSc, Daniel Howdon PhD, Delia P Muir BA, Taposhi Nath BSc, Sonia Newman PG Dip, Thomas
Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. This randomised
-
Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial Lancet (IF 168.9) Pub Date : 2023-10-12 Yuanyuan Wang PhD, Prof Graeme Jones PhD, Helen I Keen PhD, Prof Catherine L Hill MD, Prof Anita E Wluka PhD, Jessica Kasza PhD, Andrew J Teichtahl PhD, Benny Antony PhD, Richard O'Sullivan FRANZCR, Prof Flavia M Cicuttini PhD
Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis. In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged
-
Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial Lancet (IF 168.9) Pub Date : 2023-10-11 Prof Martin Bendszus MD, Prof Jens Fiehler MD, Fabien Subtil PhD, Susanne Bonekamp DVM, Anne Hege Aamodt MD, Prof Blanca Fuentes MD, Prof Elke R Gizewski MD, Prof Michael D Hill MD, Prof Antonin Krajina MD, Prof Laurent Pierot MD PhD, Prof Claus Z Simonsen MD, Prof Kamil Zeleňák MD, Rolf A Blauenfeldt MD, Bastian Cheng MD, Angélique Denis MSc, Prof Hannes Deutschmann MD, Prof Franziska Dorn MD, Fabian
Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation
-
Integrated management of HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-AFRICA): a pragmatic cluster-randomised, controlled trial Lancet (IF 168.9) Pub Date : 2023-10-05 Sokoine Kivuyo MPhil, Josephine Birungi MSc, Joseph Okebe PhD, Prof Duolao Wang PhD, Prof Kaushik Ramaiya MMed, Samafilan Ainan MMed, Faith Tumuhairwe MSc, Simple Ouma MPH, Ivan Namakoola MSc, Anupam Garrib MSc, Erik van Widenfelt BSc, Gerald Mutungi MPH, Gerard Abou Jaoude MSc, Neha Batura PhD, Joshua Musinguzi MPH, Mina Nakawuka Ssali MPH, Bernard Michael Etukoit MPH, Kenneth Mugisha MPH, Meshack
In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium
-
Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study Lancet (IF 168.9) Pub Date : 2023-10-05 Prof Deb Schrag MD, Prof Tomasz M Beer MD, Charles H McDonnell III MD, Lincoln Nadauld MD, Christina A Dilaveri MD, Robert Reid MD, Catherine R Marinac PhD, Karen C Chung MS, Margarita Lopatin MS, Eric T Fung MD PhD, Prof Eric A Klein MD
Multicancer early detection (MCED) blood tests can detect a cancer signal from circulating cell-free DNA (cfDNA). PATHFINDER was a prospective cohort study investigating the feasibility of MCED testing for cancer screening. In this prospective cohort study done in oncology and primary care outpatient clinics at seven US health networks, a convenience sample of adults aged 50 years or older without
-
National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis Lancet (IF 168.9) Pub Date : 2023-10-05 Eric O Ohuma PhD, Ann-Beth Moller MPH, Ellen Bradley MSc, Samuel Chakwera MSc, Laith Hussain-Alkhateeb PhD, Alexandra Lewin PhD, Yemisrach B Okwaraji PhD, Wahyu Retno Mahanani MSc, Emily White Johansson PhD, Tina Lavin PhD, Diana Estevez Fernandez MSc, Giovanna Gatica Domínguez PhD, Ayesha de Costa MD, Jenny A Cresswell PhD, Julia Krasevec MSc, Joy E Lawn PhD, Hannah Blencowe PhD, Jennifer Requejo
Preterm birth is the leading cause of neonatal mortality and is associated with long-term physical, neurodevelopmental, and socioeconomic effects. This study updated national preterm birth rates and trends, plus novel estimates by gestational age subgroups, to inform progress towards global health goals and targets, and aimed to update country, regional, and global estimates of preterm birth for 2020
-
Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-09-28 Catherine M Broome MD, Vickie McDonald MD, Yoshitaka Miyakawa MD, Monica Carpenedo MD, David J Kuter MD, Hanny Al-Samkari MD, James B Bussel MD, Marie Godar PhD, Jaume Ayguasanosa MD, Kristof De Beuf PhD, Francesco Rodeghiero MD, Marc Michel MD, Adrian Newland MA, ADVANCE Investigator Study Group, Michael Fillitz, Paul Knoebl, Stef Meers, Ismail Mohamad Amine, Jaromir Gumulec, Antonin Hlusi, Jiri Mayer
Primary immune thrombocytopenia is an autoimmune disorder mediated partly by platelet autoantibodies, resulting in thrombocytopenia, bleeding, and constitutional symptoms. Efgartigimod, a first-in-class novel human IgG1 Fc fragment, binds the neonatal Fc receptor with high affinity and thus reduces serum IgG concentrations, including autoantibodies. The objective of this study was to evaluate the efficacy
-
Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial Lancet (IF 168.9) Pub Date : 2023-09-19 Prof Akimichi Morita MD, Bruce Strober MD, Prof A David Burden MD, Siew Eng Choon MD, Prof Milan J Anadkat MD, Slaheddine Marrakchi MD, Prof Tsen-Fang Tsai MD, Prof Kenneth B Gordon MD, Prof Diamant Thaçi MD, Prof Min Zheng MD, Na Hu PhD, Thomas Haeufel MD, Christian Thoma MD, Prof Mark G Lebwohl MD
Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved to treat generalised pustular psoriasis (GPP) flares. We aimed to assess the efficacy and safety of spesolimab for GPP flare prevention. This multicentre, randomised, placebo-controlled, phase 2b trial was done at 60 hospitals and clinics in 20 countries. Eligible study participants were aged between 12 and 75 years with a documented
-
Role of preoperative in-hospital delay on appendiceal perforation while awaiting appendicectomy (PERFECT): a Nordic, pragmatic, open-label, multicentre, non-inferiority, randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-09-14 Karoliina Jalava MD, Ville Sallinen MD, Hanna Lampela MD, Hanna Malmi MD, Ingeborg Steinholt MD, Knut Magne Augestad MD, Ari Leppäniemi MD, Panu Mentula MD
Appendicectomy remains the standard treatment for appendicitis. No international consensus exists on the surgical urgency for acute uncomplicated appendicitis, and recommendations vary from surgery without delay to surgery within 24 h. Longer in-hospital delay has been thought to increase the risk of perforation and further morbidity. Therefore, we aimed to compare the rate of appendiceal perforation
-
NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-09-11 Zev A Wainberg MD, Davide Melisi MD, Teresa Macarulla MD, Roberto Pazo Cid MD, Sreenivasa R Chandana MD, Christelle De La Fouchardière MD, Andrew Dean MD, Igor Kiss MD, Woo Jin Lee MD, Thorsten O Goetze MD, Eric Van Cutsem MD, A Scott Paulson MD, Tanios Bekaii-Saab MD, Shubham Pant MD, Richard A Hubner MD, Zhimin Xiao MD, Huanyu Chen PhD, Fawzi Benzaghou MD, Eileen M O'Reilly MD
Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies, with few treatment options. NAPOLI 3 aimed to compare the efficacy and safety of NALIRIFOX versus nab-paclitaxel and gemcitabine as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC). NAPOLI 3 was a randomised, open-label, phase 3 study conducted at 187 community and academic sites in 18 countries
-
Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-09-08 Arshad M Khanani MD, Sunil S Patel MD, Prof Giovanni Staurenghi MD, Prof Ramin Tadayoni MD, Carl J Danzig MD, David A Eichenbaum MD, Jason Hsu MD, Charles C Wykoff MD, Jeffrey S Heier MD, David R Lally MD, Jordi Monés MD, Jared S Nielsen MD, Veeral S Sheth MD, Prof Peter K Kaiser MD, Julie Clark MD, Liansheng Zhu PhD, Hersh Patel OD, Justin Tang PhD, Dhaval Desai PharmD, Prof Glenn J Jaffe MD, GATHER2
Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth. GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic
-
Home-based monitoring of ovulation to time frozen embryo transfers in the Netherlands (Antarctica-2): an open-label, nationwide, randomised, non-inferiority trial Lancet (IF 168.9) Pub Date : 2023-09-04 Tjitske Zaat MD, Jan-Peter de Bruin MD, Prof Mariëtte Goddijn MD, Marchien van Baal MD, Sofie Benneheij MD, Monique Brandes MD, Prof Frank Broekmans MD, Astrid Cantineau MD, Ben Cohlen MD, Jeroen van Disseldorp MD, Susanne Gielen MD, Eva Groenewoud MD, Arne van Heusden MD, Eugenie Kaaijk MD, Carolien Koks MD, Corry de Koning MD, Nicole Klijn MD, Paul van der Linden MD, Petra Manger MD, Lobke Moolenaar
The growing field of assisted reproductive techniques, including frozen-thawed embryo transfer (FET), should lead the way to the best sustainable health care without compromising pregnancy chances. Correct timing of FET is crucial to allow implantation of the thawed embryo. Nowadays, timing based on hospital-controlled monitoring of ovulation in the natural cycle of a woman is the preferred strategy
-
Outcomes of repeat transcatheter aortic valve replacement with balloon-expandable valves: a registry study Lancet (IF 168.9) Pub Date : 2023-08-31 Prof Raj R Makkar MD, Prof Samir Kapadia MD, Tarun Chakravarty MD, Prof Robert J Cubeddu MD, Prof Tsuyoshi Kaneko MD, Prof Paul Mahoney MD, Dhairya Patel MPH, Aakriti Gupta MD, Wen Cheng MD, Prof Susheel Kodali MD, Prof Deepak L Bhatt MD, Prof Michael J Mack MD, Prof Martin B Leon MD, Prof Vinod H Thourani MD
With increasing numbers of patients undergoing transcatheter aortic valve replacement (TAVR), data on management of failed TAVR, including repeat TAVR procedure, are needed. The aim of this study was to assess the safety and efficacy of redo-TAVR in a national registry. This study included all consecutive patients in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve
-
Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial Lancet (IF 168.9) Pub Date : 2023-08-27 Tiffany Patterson PhD, Prof Gavin D Perkins MD, Alexander Perkins MSc, Tim Clayton MSc, Richard Evans BA, Matthew Dodd MSc, Steven Robertson BA, Karen Wilson MSc, Adam Mellett-Smith MSc, Prof Rachael T Fothergill PhD, Paul McCrone PhD, Miles Dalby MD, Prof Philip MacCarthy MD, Sam Firoozi MBBS, Prof Iqbal Malik PhD, Roby Rakhit MD, Ajay Jain MD, Prof Jerry P Nolan PhD, Prof Simon R Redwood MD, ARREST
The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18
-
Venoarterial extracorporeal membrane oxygenation in patients with infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trials Lancet (IF 168.9) Pub Date : 2023-08-26 Prof Uwe Zeymer MD, Anne Freund MD, Matthias Hochadel PhD, Prof Petr Ostadal MD, Prof Jan Belohlavek MD, Prof Richard Rokyta MD, Prof Steffen Massberg MD, Stefan Brunner MD, Enzo Lüsebrink MD, Marcus Flather MD, David Adlam MD, Prof Kris Bogaerts PhD, Amerjeet Banning PhD, Prof Manel Sabaté MD, Prof Ibrahim Akin MD, Alexander Jobs MD, Steffen Schneider PhD, Prof Steffen Desch MD, Prof Holger Thiele
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients with cardiogenic shock despite the lack of evidence from adequately powered randomised clinical trials. Three trials reported so far were underpowered to detect a survival benefit; we therefore conducted an individual patient-based meta-analysis to assess the effect of VA-ECMO on 30-day death rate. Randomised
-
Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial Lancet (IF 168.9) Pub Date : 2023-08-25 David Conen MD, Michael Ke Wang MD, Ekaterine Popova MD, Prof Matthew T V Chan PhD, Prof Giovanni Landoni MD, Juan P Cata MD, Cara Reimer MD, Sean R McLean MD, Sadeesh K Srinathan MD, Juan Carlos Trujillo Reyes PhD, Ascension Martín Grande MD, Anna Gonzalez Tallada MD, Prof Daniel I Sessler MD, Edith Fleischmann MD, Barbara Kabon MD, Luca Voltolini MD, Patrícia Cruz PhD, Prof Donna E Maziak MDCM, Prof
Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac
-
Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials Lancet (IF 168.9) Pub Date : 2023-08-25 Prof Charles B Majoie PhD, Fabiano Cavalcante MD, Prof Jan Gralla MD, Prof Pengfei Yang MD, Johannes Kaesmacher PhD, Kilian M Treurniet PhD, Manon Kappelhof PhD, Prof Bernard Yan DMedSci, Kentaro Suzuki PhD, Prof Yongwei Zhang MD, Fengli Li MD, Masafumi Morimoto PhD, Prof Lei Zhang MD, Prof Zhongrong Miao MD, Leon A Rinkel MD, Jiacheng Huang MD, Toshiaki Otsuka PhD, Prof Shouchun Wang MD, Prof Stephen
Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke
-
Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-08-24 Prof Bruce L Wilkoff MD, Prof Gerasimos Filippatos MD, Prof Christophe Leclercq MD, Prof Michael R Gold MD, Prof Ahmad S Hersi MD, Kengo Kusano MD, Prof Wilfried Mullens MD, Prof G Michael Felker MD, Charan Kantipudi MD, Prof Mikhael F El-Chami MD, Prof Vidal Essebag MD, Bertrand Pierre MD, Francois Philippon MD, Francisco Perez-Gil MD, Eugene S Chung MD, Juan Sotomonte MD, Stanley Tung MD, Balbir
Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of
-
Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-08-23 Hope S Rugo MD, Aditya Bardia MD, Frederik Marmé MD, Javier Cortés MD, Peter Schmid MD, Delphine Loirat MD, Olivier Trédan MD, Eva Ciruelos MD, Florence Dalenc MD, Patricia Gómez Pardo MD, Komal L Jhaveri MD, Rosemary Delaney MPH, Theresa Valdez PharmD, Hao Wang PhD, Monica Motwani PhD, Oh Kyu Yoon PhD, Wendy Verret PhD, Sara M Tolaney MD
Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in patients with pretreated, endocrine-resistant hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2–) metastatic breast cancer with limited treatment options. Here, we report the protocol-specified final analysis of overall survival
-
Immune response after pig-to-human kidney xenotransplantation: a multimodal phenotyping study Lancet (IF 168.9) Pub Date : 2023-08-17 Prof Alexandre Loupy MD PhD, Valentin Goutaudier MD MSc, Alessia Giarraputo PhD, Fariza Mezine MSc, Erwan Morgand PhD, Blaise Robin MSc, Karen Khalil PharmD, Sapna Mehta MD, Brendan Keating PhD, Amy Dandro MSc, Anaïs Certain MSc, Pierre-Louis Tharaux MD PhD, Prof Navneet Narula MD, Prof Renaud Tissier DVM PhD, Sébastien Giraud PhD, Prof Thierry Hauet MD PhD, Prof Harvey I Pass MD, Aurélie Sannier MD
Cross-species immunological incompatibilities have hampered pig-to-human xenotransplantation, but porcine genome engineering recently enabled the first successful experiments. However, little is known about the immune response after the transplantation of pig kidneys to human recipients. We aimed to precisely characterise the early immune responses to the xenotransplantation using a multimodal deep