Efficacy of Therapeutic Heparin Compared to Prophylactic Heparin on Death, Mechanical Ventilation, or Intensive Care Unit Admission in Moderately Ill Patients with Covid-19 Admitted to Hospital: RAPID Randomized Clinical Trial

BMJ. October 14, 2021; 375: n2400. doi: 10.1136 / bmj.n2400.

ABSTRACT

OBJECTIVE: To assess the effects of therapeutic heparin compared to prophylactic heparin in moderately ill patients with covid-19 admitted to hospital wards.

DESIGN: Randomized controlled, adaptive, open-label clinical trial.

SETTING: 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates and United States.

PARTICIPANTS: 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between May 29, 2020 and April 12, 2021 and were randomized to receive a therapeutic dose of heparin (n = 228 ) or a prophylactic dose of heparin (n = 237).

INTERVENTIONS: Therapeutic dose or prophylactic dose of heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28 or death.

MAIN OUTCOME MEASURES: The primary outcome measure was a composite outcome of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, evaluated for up to 28 days. Secondary outcomes included all-cause death, composite of all-cause death or any mechanical ventilation, and venous thromboembolism. Safety results included major bleeding. The results were blindly evaluated.

RESULTS: The average age of the participants was 60 years; 264 (56.8%) were male and the mean body mass index was 30.3 kg / m2. At 28 days, the composite primary outcome was observed in 37,228 (16.2%) patients assigned to therapeutic heparin and 52/237 (21.9%) 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 death from any cause or from 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 an increased level of D-dimer admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary endpoint, but the risk death at 28 days was reduced. The risk of major bleeding appeared to be low in this trial.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04362085.

PMID: 34649864 | DOI: 10.1136 / bmj.n2400


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