1. 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
- Author
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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, Laupacis, Andreas, Lin, Yulia, Day, Andrew, Rochwerg, Bram, Abdulrehman, Jameel, Gergi, Mansour, Kondo, Rodrigo Hidd, Piloto, Bruna Mamprim, de Abreu Pereira, Guilherme, Valente, Fernando Salvetti, Agreda, Ariel Fernando Villarroel, Munoz Torres, Pablo Andres, Moraes, Maíra Oliveira, de Lucena Moreira, Claudia, Neto, Fernando Galassi Stocco, Baptista, Fabíola Vieira Duarte, Moreira, Joanne Alves, Ferreira, Augusto Séttemo, Frudit, Paula, Martinez, Gabriel, Souza, Heraldo Possolo, Neto, Rodrigo Antônio Brandão, d'Amico, Elbio Antonio, Padrão, Eduardo Messias Hirano, Sarin da Mota e Albuquerque, Fernando, Zangrossi, Giovanna Villela, Kanasiro, Alberto Kendy, Cincoto, Alissom Vitti, de Souza Reis, Hugo, Arias da Silva, Vitor Miyashiro, Bellintani, Arthur Petrillo, dos Santos Pereira, Vivian, de Oliveira, Yohan Washington, Carvalho, Bárbara Justo, de Souza Novaes, Mariana, Silveira, Henrique Brito, de Avelar, Gabriel César Alves, Mota, Lara Bonanni, Caciola, Karina, Marim, Matheus de Arêa Leão Freire, Monsalvarga, Tales Cabral, Blanco Santos, Alexandre Salgado, Haydar, Ahmed, Saraiva, Gabriella Seixas Sampaio, da Costa Ribeiro, Sabrina Correa, Meirelles Marchini, Julio Flavio, de Alencar, Julio Cesar Garcia, de Seixas Santos, Ana Catharina, Millette, Caroline, Lebeau, Mathieu, Devaux, Céline, Boutin, Mélina, Nguyen, Trung Nghia, Srour, Line, de Angelis, Flavia, Fugulin, Mariane, Binnie, Alexandra, Bejaimal, Shayna A.D., Binding, Andrew, Marticorena, Rosa M., Ginocchio, Galo, Kaplovitch, Eric, Rymaszewski, Klaudia, Raissi, Afsaneh, Falappa, Marcelo, Ernst, Blair, Ali, Amna, Romano, Martin, Khurram, Mobina, Kim, Christie, Kapur, Ajay, Edwards, Michelle, Swarup, Vidushi, Camilotti, Bruna, Jani, Jiten, Carter, Jeff, Gillrie, Mark R., Sidhu, Davinder, Robinson, Traci, Stutely, Krystina, Watpool, Irene, Porteous, Rebecca, Jao, Kevin, Boudreault-Pedneault, Jean-Samuel, Kandel, Christopher, Taylor, Maureen T., Choo, Wei En Enoch, Parsons, Laura, Dowbenka, Ann, Ramonas, Gitana, Nikitin, Sergey, Patterson, Jeffery, Hnatiuk, Mark, Tapardel, Anca, Lapner, Sarah Takach, Carpenter, Thirza, Rackel, Lori, Cairns, Rebecca, Pinder, Jessica, Anglin, Peter, McPherson, Catherine, Chiverton, Liselle, Barbosa, David, Loukiantchenko, Shany, Shamiss, Yana, Tassy, Danaë, Shivakumar, Sudeep, Keating, Mary-Margaret, Pleasance, Sue, Kevane, Barry, Cullivan, Sarah, Power, Nick, Doran, Peter, Leamy, Kelly, Kelly, Aoife, Moran, Conor, O'Connor, Mairead, McDonnell, Aoife, Boyce, Roseanne, Sefroun, Faiza, Hussain, Rabia, Murray, Patrick, Malara, Anna, Molloy, Brenda, O’Halloran, Meadbh, Cunningham, Emer, Lambert, Jack, Cotter, Aoife, Marsh, Brian, Sheehan, Gerard, Muldoon, Eavan, Woo, James, Gaine, Sean, Morley, Deirdre, AlGahtani, Farjah H, Almaghlouth, Ibrahim, Ata, Sondus, Alkhathlan, Fai, Khalil, Najma, Hussein, Israa Mohamed, Bashir, Mohammed, BaHammam, Ahmed S, Alsultan, Abdulrahman, Alkofide, Hadeel, Alhawassi, Tariq M, Alqahtani, Abdulhadi M., Zayed, Emad K., AlSughayir, Ammar, Abuzied, Yacoub, AlZahrani, Hazzaa, Al-Otaibi, Jawaher, Alothaimeen, Haya, Alzannan, Noura, Al Homssi, Amer, Abid, Haisam, Jones, Stephanie, Broaddrick, Shannon, Jain, Neha, King, Roz, Jindal, Mohit, Sanfilippo, Kristen, Nieters, Patty, Hammad, Muhammad, Benny, Aleeswa Francis, Hamdan, Tariq A., Elobaid, Suhaib Kamal Ahmed, Khafagi, Ibrahim, Ahmed, Saima Saeed, AlEssaie, AbduleRehman, AlAlawi, Shamma, Bashir, Khloud, Al Suwaidi, Aysha Abdulla Salem, Ahmed, Hiba Ibrahim Khogali, Ismail, Mohamed Milad, El Faki, El Mutasim Ahmed, Charles, Mercy, Dang, Alice, Lakhanpal, Gurpreet, Lee, Dominic, Ray, Prachi, Naydenova, Maria, Wysocki, Kosma, Jiwajee, Aziz, Wendling, Greg, Boyle, Rebekah, Cornell, Elaine, Mukaz, Debora Kamin, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, and ARD - Amsterdam Reproduction and Development
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,610 Medicine & health ,Severity of Illness Index ,law.invention ,All institutes and research themes of the Radboud University Medical Center ,Therapeutic index ,360 Social problems & social services ,law ,Internal medicine ,Severity of illness ,medicine ,Humans ,Mechanical ventilation ,Heparin ,SARS-CoV-2 ,business.industry ,Research ,Anticoagulants ,COVID-19 ,General Medicine ,Odds ratio ,Middle Aged ,Respiration, Artificial ,Intensive care unit ,Hospitalization ,Clinical trial ,Intensive Care Units ,Female ,business ,Body mass index ,Biomarkers ,medicine.drug - 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 .
- Published
- 2021