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.
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.
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DOI：
10.1136/bmj.n2400
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发表时间：
2021-10-14
期刊：
影响因子：
--
通讯作者：
RAPID trial investigators
中科院分区：
文献类型：
--
作者：
Sholzberg M;Tang GH;Rahhal H;AlHamzah M;Kreuziger LB;Áinle FN;Alomran F;Alayed K;Alsheef M;AlSumait F;Pompilio CE;Sperlich C;Tangri S;Tang T;Jaksa P;Suryanarayan D;Almarshoodi M;Castellucci LA;James PD;Lillicrap D;Carrier M;Beckett A;Colovos C;Jayakar J;Arsenault MP;Wu C;Doyon K;Andreou ER;Dounaevskaia V;Tseng EK;Lim G;Fralick M;Middeldorp S;Lee AYY;Zuo F;da Costa BR;Thorpe KE;Negri EM;Cushman M;Jüni P;RAPID trial investigators
评价治疗性肝素与预防性肝素在住院的中度COVID-19患者中的效果。随机对照、适应性、开放标签临床试验。巴西、加拿大、爱尔兰、沙特阿拉伯、阿拉伯联合酋长国和美国的28家医院。在2020年5月29日至2021年4月12日期间，招募了465名因Covid-19和D-二聚体水平升高而入住医院病房的成年人，并随机分配至治疗剂量肝素（n=228）或预防剂量肝素（n=237）。治疗剂量或预防剂量肝素（低分子量或普通肝素），持续至出院、第28天或死亡。主要结局是死亡、有创机械通气、无创机械通气或入住重症监护室的复合终点，评估时间长达28天。次要结局包括全因死亡、全因死亡或任何机械通气的复合终点和静脉血栓栓塞。安全性结局包括大出血。对结局进行盲法判定。参与者的平均年龄为60岁; 264名（56.8%）为男性，平均体重指数为30.3 kg/m2。在第28天时，37/228例（16.2%）接受治疗性肝素的患者和52/237例（21.9%）接受预防性肝素的患者发生了主要复合结局（比值比0.69，95%置信区间0.43 - 1.10; P=0.12）。4例（1.8%）分配至治疗性肝素组的患者和18例（7.6%）分配至预防性肝素组的患者发生死亡（0.22，0.07 - 0.65; P=0.006）。23例（10.1%）接受治疗性肝素治疗的患者和38例（16.0%）接受预防性肝素治疗的患者发生了全因死亡或任何机械通气的复合终点（0.59，0.34 - 1.02; P=0.06）。2例（0.9%）接受治疗性肝素治疗的患者和6例（2.5%）接受预防性肝素治疗的患者发生静脉血栓栓塞（0.34，0.07 - 1.71; P=0.19）。2例（0.9%）接受治疗性肝素治疗的患者和4例（1.7%）接受预防性肝素治疗的患者发生了大出血（0.52，0.09 - 2.85; P=0.69）。在住院的COVID-19和D-二聚体水平升高的中度患者中，治疗性肝素与主要结局的降低无显著相关性，但28天死亡的几率降低。本试验中大出血的风险似乎较低。ClinicalTrials.gov NCT 04362085。
To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. Randomised controlled, adaptive, open label clinical trial. 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. 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). Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. 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. 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). 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. ClinicalTrials.gov NCT04362085.
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影响因子：
5.8
作者：
Mu S;Liu Y;Jiang J;Ding R;Li X;Li X;Ma X
通讯作者：
Ma X
影响因子：
4
作者：
Negri EM;Piloto BM;Morinaga LK;Jardim CVP;Lamy SAE;Ferreira MA;D'Amico EA;Deheinzelin D
通讯作者：
Deheinzelin D
影响因子：
9.6
作者：
Kearon, Clive;Akl, Elie A.;Moores, Lisa
通讯作者：
Moores, Lisa
DOI：
10.1155/2013/910743
发表时间：
2013
期刊：
ISRN pharmacology
影响因子：
--
作者：
Page C
通讯作者：
Page C
影响因子：
10.4
作者：
Middeldorp, Saskia;Coppens, Michiel;van Es, Nick
通讯作者：
van Es, Nick