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(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
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/m2. 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.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:375 |
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| Enthalten in: |
BMJ (Clinical research ed.) - 375(2021) vom: 14. Okt., Seite n2400 |
| Sprache: |
Englisch |
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| Links: |
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| Themen: |
9005-49-6 |
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| Anmerkungen: |
Date Completed 21.10.2021 Date Revised 16.02.2022 published: Electronic ClinicalTrials.gov: NCT04362085 UpdateOf: medRxiv. 2021 Jul 12;:. - PMID 34268513 Citation Status MEDLINE |
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| doi: |
10.1136/bmj.n2400 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM331905930 |
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| 100 | 1 | |a Sholzberg, Michelle |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |b RAPID randomised clinical trial |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.10.2021 | ||
| 500 | |a Date Revised 16.02.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04362085 | ||
| 500 | |a UpdateOf: medRxiv. 2021 Jul 12;:. - PMID 34268513 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a OBJECTIVE: To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards | ||
| 520 | |a DESIGN: Randomised controlled, adaptive, open label clinical trial | ||
| 520 | |a SETTING: 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US | ||
| 520 | |a 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) | ||
| 520 | |a INTERVENTIONS: Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death | ||
| 520 | |a 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 | ||
| 520 | |a RESULTS: The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m2. 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) | ||
| 520 | |a 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 | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov NCT04362085 | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anticoagulants |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Heparin |2 NLM | |
| 650 | 7 | |a 9005-49-6 |2 NLM | |
| 700 | 1 | |a Tang, Grace H |e verfasserin |4 aut | |
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| 700 | 1 | |a Kreuziger, Lisa Baumann |e verfasserin |4 aut | |
| 700 | 1 | |a Áinle, Fionnuala Ní |e verfasserin |4 aut | |
| 700 | 1 | |a Alomran, Faris |e verfasserin |4 aut | |
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| 700 | 1 | |a Alsheef, Mohammed |e verfasserin |4 aut | |
| 700 | 1 | |a AlSumait, Fahad |e verfasserin |4 aut | |
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| 700 | 1 | |a Tangri, Sabrena |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Terence |e verfasserin |4 aut | |
| 700 | 1 | |a Jaksa, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Suryanarayan, Deepa |e verfasserin |4 aut | |
| 700 | 1 | |a Almarshoodi, Mozah |e verfasserin |4 aut | |
| 700 | 1 | |a Castellucci, Lana A |e verfasserin |4 aut | |
| 700 | 1 | |a James, Paula D |e verfasserin |4 aut | |
| 700 | 1 | |a Lillicrap, David |e verfasserin |4 aut | |
| 700 | 1 | |a Carrier, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Beckett, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Colovos, Christos |e verfasserin |4 aut | |
| 700 | 1 | |a Jayakar, Jai |e verfasserin |4 aut | |
| 700 | 1 | |a Arsenault, Marie-Pier |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Cynthia |e verfasserin |4 aut | |
| 700 | 1 | |a Doyon, Karine |e verfasserin |4 aut | |
| 700 | 1 | |a Andreou, E Roseann |e verfasserin |4 aut | |
| 700 | 1 | |a Dounaevskaia, Vera |e verfasserin |4 aut | |
| 700 | 1 | |a Tseng, Eric K |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Gloria |e verfasserin |4 aut | |
| 700 | 1 | |a Fralick, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Middeldorp, Saskia |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Agnes Y Y |e verfasserin |4 aut | |
| 700 | 1 | |a Zuo, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a da Costa, Bruno R |e verfasserin |4 aut | |
| 700 | 1 | |a Thorpe, Kevin E |e verfasserin |4 aut | |
| 700 | 1 | |a Negri, Elnara Márcia |e verfasserin |4 aut | |
| 700 | 1 | |a Cushman, Mary |e verfasserin |4 aut | |
| 700 | 1 | |a Jüni, Peter |e verfasserin |4 aut | |
| 700 | 0 | |a RAPID trial investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Laupacis, Andreas |e investigator |4 oth | |
| 700 | 1 | |a Lin, Yulia |e investigator |4 oth | |
| 700 | 1 | |a Day, Andrew |e investigator |4 oth | |
| 700 | 1 | |a Rochwerg, Bram |e investigator |4 oth | |
| 700 | 1 | |a Abdulrehman, Jameel |e investigator |4 oth | |
| 700 | 1 | |a Gergi, Mansour |e investigator |4 oth | |
| 700 | 1 | |a Kondo, Rodrigo Hidd |e investigator |4 oth | |
| 700 | 1 | |a Piloto, Bruna Mamprim |e investigator |4 oth | |
| 700 | 1 | |a de Abreu Pereira, Guilherme |e investigator |4 oth | |
| 700 | 1 | |a Valente, Fernando Salvetti |e investigator |4 oth | |
| 700 | 1 | |a Agreda, Ariel Fernando Villarroel |e investigator |4 oth | |
| 700 | 1 | |a Munoz Torres, Pablo Andres |e investigator |4 oth | |
| 700 | 1 | |a Moraes, Maíra Oliveira |e investigator |4 oth | |
| 700 | 1 | |a de Lucena Moreira, Claudia |e investigator |4 oth | |
| 700 | 1 | |a Neto, Fernando Galassi Stocco |e investigator |4 oth | |
| 700 | 1 | |a Baptista, Fabíola Vieira Duarte |e investigator |4 oth | |
| 700 | 1 | |a Moreira, Joanne Alves |e investigator |4 oth | |
| 700 | 1 | |a Ferreira, Augusto Séttemo |e investigator |4 oth | |
| 700 | 1 | |a Frudit, Paula |e investigator |4 oth | |
| 700 | 1 | |a Martinez, Gabriel |e investigator |4 oth | |
| 700 | 1 | |a Souza, Heraldo Possolo |e investigator |4 oth | |
| 700 | 1 | |a Neto, Rodrigo Antônio Brandão |e investigator |4 oth | |
| 700 | 1 | |a d'Amico, Elbio Antonio |e investigator |4 oth | |
| 700 | 1 | |a Padrão, Eduardo Messias Hirano |e investigator |4 oth | |
| 700 | 1 | |a Sarin da Mota E Albuquerque, Fernando |e investigator |4 oth | |
| 700 | 1 | |a Zangrossi, Giovanna Villela |e investigator |4 oth | |
| 700 | 1 | |a Kanasiro, Alberto Kendy |e investigator |4 oth | |
| 700 | 1 | |a Cincoto, Alissom Vitti |e investigator |4 oth | |
| 700 | 1 | |a de Souza Reis, Hugo |e investigator |4 oth | |
| 700 | 1 | |a Arias da Silva, Vitor Miyashiro |e investigator |4 oth | |
| 700 | 1 | |a Bellintani, Arthur Petrillo |e investigator |4 oth | |
| 700 | 1 | |a Dos Santos Pereira, Vivian |e investigator |4 oth | |
| 700 | 1 | |a de Oliveira, Yohan Washington |e investigator |4 oth | |
| 700 | 1 | |a Carvalho, Bárbara Justo |e investigator |4 oth | |
| 700 | 1 | |a de Souza Novaes, Mariana |e investigator |4 oth | |
| 700 | 1 | |a Silveira, Henrique Brito |e investigator |4 oth | |
| 700 | 1 | |a de Avelar, Gabriel César Alves |e investigator |4 oth | |
| 700 | 1 | |a Mota, Lara Bonanni |e investigator |4 oth | |
| 700 | 1 | |a Caciola, Karina |e investigator |4 oth | |
| 700 | 1 | |a Marim, Matheus de Arêa Leão Freire |e investigator |4 oth | |
| 700 | 1 | |a Monsalvarga, Tales Cabral |e investigator |4 oth | |
| 700 | 1 | |a Blanco Santos, Alexandre Salgado |e investigator |4 oth | |
| 700 | 1 | |a Haydar, Ahmed |e investigator |4 oth | |
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| 700 | 1 | |a da Costa Ribeiro, Sabrina Correa |e investigator |4 oth | |
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| 700 | 1 | |a Millette, Caroline |e investigator |4 oth | |
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| 700 | 1 | |a Devaux, Céline |e investigator |4 oth | |
| 700 | 1 | |a Boutin, Mélina |e investigator |4 oth | |
| 700 | 1 | |a Nguyen, Trung Nghia |e investigator |4 oth | |
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| 700 | 1 | |a de Angelis, Flavia |e investigator |4 oth | |
| 700 | 1 | |a Fugulin, Mariane |e investigator |4 oth | |
| 700 | 1 | |a Binnie, Alexandra |e investigator |4 oth | |
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| 700 | 1 | |a Swarup, Vidushi |e investigator |4 oth | |
| 700 | 1 | |a Camilotti, Bruna |e investigator |4 oth | |
| 700 | 1 | |a Jani, Jiten |e investigator |4 oth | |
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| 700 | 1 | |a Gillrie, Mark R |e investigator |4 oth | |
| 700 | 1 | |a Sidhu, Davinder |e investigator |4 oth | |
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| 700 | 1 | |a Watpool, Irene |e investigator |4 oth | |
| 700 | 1 | |a Porteous, Rebecca |e investigator |4 oth | |
| 700 | 1 | |a Jao, Kevin |e investigator |4 oth | |
| 700 | 1 | |a Boudreault-Pedneault, Jean-Samuel |e investigator |4 oth | |
| 700 | 1 | |a Kandel, Christopher |e investigator |4 oth | |
| 700 | 1 | |a Taylor, Maureen T |e investigator |4 oth | |
| 700 | 1 | |a Choo, Wei En Enoch |e investigator |4 oth | |
| 700 | 1 | |a Parsons, Laura |e investigator |4 oth | |
| 700 | 1 | |a Dowbenka, Ann |e investigator |4 oth | |
| 700 | 1 | |a Ramonas, Gitana |e investigator |4 oth | |
| 700 | 1 | |a Nikitin, Sergey |e investigator |4 oth | |
| 700 | 1 | |a Patterson, Jeffery |e investigator |4 oth | |
| 700 | 1 | |a Hnatiuk, Mark |e investigator |4 oth | |
| 700 | 1 | |a Tapardel, Anca |e investigator |4 oth | |
| 700 | 1 | |a Lapner, Sarah Takach |e investigator |4 oth | |
| 700 | 1 | |a Carpenter, Thirza |e investigator |4 oth | |
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| 700 | 1 | |a Cairns, Rebecca |e investigator |4 oth | |
| 700 | 1 | |a Pinder, Jessica |e investigator |4 oth | |
| 700 | 1 | |a Anglin, Peter |e investigator |4 oth | |
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