Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial. (14th October 2021)

• Record Type: Journal Article
• Authors: Sholzberg, Michelle; Tang, Grace H; Rahhal, Hassan; AlHamzah, Musaad; Kreuziger, Lisa Baumann; Áinle, Fionnuala Ní; Alomran, Faris; Alayed, Khalid; Alsheef, Mohammed; AlSumait, Fahad; Pompilio, Carlos Eduardo; Sperlich, Catherine; Tangri, Sabrena; Tang, Terence; Jaksa, Peter; Suryanarayan, Deepa; Almarshoodi, Mozah; Castellucci, Lana A; James, Paula D; Lillicrap, David; Carrier, Marc; Beckett, Andrew; Colovos, Christos; Jayakar, Jai; Arsenault, Marie-Pier; Wu, Cynthia; Doyon, Karine; Andreou, E Roseann; Dounaevskaia, Vera; Tseng, Eric K; Lim, Gloria; Fralick, Michael; Middeldorp, Saskia; Lee, Agnes Y Y; Zuo, Fei; da Costa, Bruno R; Thorpe, Kevin E; Negri, Elnara Márcia; Cushman, Mary; Jüni, Peter;
• Other Names: author non-byline.; Laupacis Andreas author non-byline.; Lin Yulia author non-byline.; Day Andrew author non-byline.; Rochwerg Bram author non-byline.; Abdulrehman Jameel author non-byline.; Gergi Mansour author non-byline.; Kondo Rodrigo Hidd author non-byline.; Piloto Bruna Mamprim author non-byline.; de Abreu Pereira Guilherme author non-byline.; Valente Fernando Salvetti author non-byline.; Agreda Ariel Fernando Villarroel author non-byline.; Munoz Torres Pablo Andres author non-byline.; Moraes Maíra Oliveira author non-byline.; de Lucena Moreira Claudia author non-byline.; Neto Fernando Galassi Stocco author non-byline.; Baptista Fabíola Vieira Duarte author non-byline.; Moreira Joanne Alves author non-byline.; Ferreira Augusto Séttemo author non-byline.; Frudit Paula author non-byline.; Martinez Gabriel author non-byline.; Souza Heraldo Possolo author non-byline.; Neto Rodrigo Antônio Brandão author non-byline.; d'Amico Elbio Antonio author non-byline.; Padrão Eduardo Messias Hirano author non-byline.; Sarin da Mota e Albuquerque Fernando author non-byline.; Zangrossi Giovanna Villela author non-byline.; Kanasiro Alberto Kendy author non-byline.; Cincoto Alissom Vitti author non-byline.; de Souza Reis Hugo author non-byline.; Arias da Silva Vitor Miyashiro author non-byline.; Bellintani Arthur Petrillo author non-byline.; dos Santos Pereira Vivian author non-byline.; de Oliveira Yohan Washington author non-byline.; Carvalho Bárbara Justo author non-byline.; de Souza Novaes Mariana author non-byline.; Silveira Henrique Brito author non-byline.; de Avelar Gabriel César Alves author non-byline.; Mota Lara Bonanni author non-byline.; Caciola Karina author non-byline.; Marim Matheus de Arêa Leão Freire author non-byline.; Monsalvarga Tales Cabral author non-byline.; Blanco Santos Alexandre Salgado author non-byline.; Haydar Ahmed author non-byline.; Saraiva Gabriella Seixas Sampaio author non-byline.; da Costa Ribeiro Sabrina Correa author non-byline.; Meirelles Marchini Julio Flavio author non-byline.; de Alencar Julio Cesar Garcia author non-byline.; de Seixas Santos Ana Catharina author non-byline.; Millette Caroline author non-byline.; Lebeau Mathieu author non-byline.; Devaux Céline author non-byline.; Boutin Mélina author non-byline.; Nguyen Trung Nghia author non-byline.; Srour Line author non-byline.; de Angelis Flavia author non-byline.; Fugulin Mariane author non-byline.; Binnie Alexandra author non-byline.; Bejaimal Shayna A.D. author non-byline.; Binding Andrew author non-byline.; Marticorena Rosa M. author non-byline.; Ginocchio Galo author non-byline.; Kaplovitch Eric author non-byline.; Rymaszewski Klaudia author non-byline.; Raissi Afsaneh author non-byline.; Falappa Marcelo author non-byline.; Ernst Blair author non-byline.; Ali Amna author non-byline.; Romano Martin author non-byline.; Khurram Mobina author non-byline.; Kim Christie author non-byline.; Kapur Ajay author non-byline.; Edwards Michelle author non-byline.; Swarup Vidushi author non-byline.; Camilotti Bruna author non-byline.; Jani Jiten author non-byline.; Carter Jeff author non-byline.; Gillrie Mark R. author non-byline.; Sidhu Davinder author non-byline.; Robinson Traci author non-byline.; Stutely Krystina author non-byline.; Watpool Irene author non-byline.; Porteous Rebecca author non-byline.; Jao Kevin author non-byline.; Boudreault-Pedneault Jean-Samuel author non-byline.; Kandel Christopher author non-byline.; Taylor Maureen T. author non-byline.; Choo Wei En Enoch author non-byline.; Parsons Laura author non-byline.; Dowbenka Ann author non-byline.; Ramonas Gitana author non-byline.; Nikitin Sergey author non-byline.; Patterson Jeffery author non-byline.; Hnatiuk Mark author non-byline.; Tapardel Anca author non-byline.; Lapner Sarah Takach author non-byline.; Carpenter Thirza author non-byline.; Rackel Lori author non-byline.; Cairns Rebecca author non-byline.; Pinder Jessica author non-byline.; Anglin Peter author non-byline.; McPherson Catherine author non-byline.; Chiverton Liselle author non-byline.; Barbosa David author non-byline.; Loukiantchenko Shany author non-byline.; Shamiss Yana author non-byline.; Tassy Danaë author non-byline.; Shivakumar Sudeep author non-byline.; Keating Mary-Margaret author non-byline.; Pleasance Sue author non-byline.; Kevane Barry author non-byline.; Cullivan Sarah author non-byline.; Power Nick author non-byline.; Doran Peter author non-byline.; Leamy Kelly author non-byline.; Kelly Aoife author non-byline.; Moran Conor author non-byline.; O'Connor Mairead author non-byline.; McDonnell Aoife author non-byline.; Boyce Roseanne author non-byline.; Sefroun Faiza author non-byline.; Hussain Rabia author non-byline.; Murray Patrick author non-byline.; Malara Anna author non-byline.; Molloy Brenda author non-byline.; O'Halloran Meadbh author non-byline.; Cunningham Emer author non-byline.; Lambert Jack author non-byline.; Cotter Aoife author non-byline.; Marsh Brian author non-byline.; Sheehan Gerard author non-byline.; Muldoon Eavan author non-byline.; Woo James author non-byline.; Gaine Sean author non-byline.; Morley Deirdre author non-byline.; AlGahtani Farjah H author non-byline.; Almaghlouth Ibrahim author non-byline.; Ata Sondus author non-byline.; Alkhathlan Fai author non-byline.; Khalil Najma author non-byline.; Hussein Israa Mohamed author non-byline.; Bashir Mohammed author non-byline.; BaHammam Ahmed S author non-byline.; Alsultan Abdulrahman author non-byline.; Alkofide Hadeel author non-byline.; Alhawassi Tariq M author non-byline.; Alqahtani Abdulhadi M. author non-byline.; Zayed Emad K. author non-byline.; AlSughayir Ammar author non-byline.; Abuzied Yacoub author non-byline.; AlZahrani Hazzaa author non-byline.; Al-Otaibi Jawaher author non-byline.; Alothaimeen Haya author non-byline.; Alzannan Noura author non-byline.; Al Homssi Amer author non-byline.; Abid Haisam author non-byline.; Jones Stephanie author non-byline.; Broaddrick Shannon author non-byline.; Jain Neha author non-byline.; King Roz author non-byline.; Jindal Mohit author non-byline.; Sanfilippo Kristen author non-byline.; Nieters Patty author non-byline.; Hammad Muhammad author non-byline.; Benny Aleeswa Francis author non-byline.; Hamdan Tariq A. author non-byline.; Elobaid Suhaib Kamal Ahmed author non-byline.; Khafagi Ibrahim author non-byline.; Ahmed Saima Saeed author non-byline.; AlEssaie AbduleRehman author non-byline.; AlAlawi Shamma author non-byline.; Bashir Khloud author non-byline.; Al Suwaidi Aysha Abdulla Salem author non-byline.; Ahmed Hiba Ibrahim Khogali author non-byline.; Ismail Mohamed Milad author non-byline.; El Faki El Mutasim Ahmed author non-byline.; Charles Mercy author non-byline.; Dang Alice author non-byline.; Lakhanpal Gurpreet author non-byline.; Lee Dominic author non-byline.; Ray Prachi author non-byline.; Naydenova Maria author non-byline.; Wysocki Kosma author non-byline.; Jiwajee Aziz author non-byline.; Wendling Greg author non-byline.; Boyle Rebekah author non-byline.; Cornell Elaine author non-byline.; Mukaz Debora Kamin author non-byline.;
• Is Part Of: BMJ. Volume 375(2021)
• Publication Date: 2021-10-14
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Periodicals; 610
• DOI: 10.1136/bmj.n2400
• Languages: English
• ISSNs: 0007-1447

Abstract

Abstract: Objective: To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. Design: Randomised controlled, adaptive, open label clinical trial. Setting: 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. Participants: 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). Interventions: Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. Main outcome measures: The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. Results: The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m 2 . At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). Conclusions: In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. Trial registration: ClinicalTrials.gov NCT04362085 .