Trial NCT04486508
Publication Bikdeli B, Thromb Haemost, 2021 (published paper)
Dates: 2020-07-29 to 2020-11-19
Funding: Mixed (Rajaie Cardiovascular Medical and Research Center. Medications and placebo were provided through Alborz Darou, Pooyesh Darou, and Caspian Pharmaceuticals companies.)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: single blinding | |
| Location :
Multicenter / Iran Follow-up duration (days): 90 | |
| Inclusion criteria | Adult patients (≥18 years) ; PCR-confirmed COVID-19 and admitted to ICU within 7 days of initial hospitalization ; no other firm indication for anticoagulation (such as mechanical valve, high-risk AF, VTE, or left ventricular thrombus) ; not enrolled in another blinded randomized trial ; willing to participate in the study and provide informed consent ; estimated survival of at least 24 hours at the discretion of enrolling physician. |
| Exclusion criteria | Weight <40Kg ; use of systemic anticoagulation for another indication (mechanical valve, ECMO, AF, left ventricular thrombus, or diagnosed VTE) ; overt bleeding at the day of enrollment ; known major bleeding within 30 days (according to the Bleeding Academic Research Consortium (BARC) definition, Appendix A) ; platelet count <50,000/Fl ; pregnancy (as confirmed by beta-HCG testing among female patients <50 years) ; history of heparin induced thrombocytopenia or immune thrombocytopenia ; ischemic stroke within the past 2 weeks ; major head or spinal trauma in the past 30 days ; craniotomy/major neurosurgery within the past 3 months ; known brain metastases or vascular malformations (aneurysm) ; presence of an epidural, spinal or pericardial catheter ; major surgery other than neurosurgery within 14 days prior to enrollment ; coexistence of severe obesity (weight >120Kg or BMI>35Kg/M2 along with severe renal insufficiency defined as CrCl<30 mL/min) ; allergic reaction to study medications ; lack or withdrawal of informed consent. |
| Interventions | |
| Treatment
Standard-Dose prophylactic anticoagulation Enoxaparin: 40 mg once daily for 30 days (dosage/times per day adjusted according to creatinine clearance and body weight; unfractionated heparin 5000 units SC twice daily only for patients with creatinine clearance of ≤15 mL/min). |
|
| Control
Intermediate-Dose prophylactic anticoagulation ( / ) | |
| Participants | |
| Randomized 598 participants (n1=299 / n2= 299) | |
| Characteristics of participants N=598 Mean age : NR 325 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=449 Critical: n=113 | |
| Primary outcome | |
| In the register A composite of acute VTE, arterial thrombosis, treatment with ECMO, or all-cause mortality [ Time Frame: 30 days from enrollment ] | |
| In the report Composite of adjudicated acute VTE, arterial thrombosis, treatment with extra- corporeal membrane oxygenation (ECMO), or all-cause mortality at 90 days from enrollment | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated Yes |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | In addition to the published articles, the trial registry, published and full protocol, statistical analysis plan, and information obtained from contact with the author were used in data extraction and assessment of risk of bias. There were no substantive differences between the published article and the trial registry and protocol in population, procedures and interventions. One long term outcome, included in the trial registry but not the protocol (post-COVID-19 functional status at 60 & 90 days), is not reported. All other outcomes for the reported comparison in the trial registry and protocol were reported. Some post hoc subgroup analyses were performed. Recruitment was paused by the data and safety monitoring board because of futility for efficacy and potential excess of safety events. On 30th of April, 2021, this study (90 Day results) was updated based on the published report in Thromb Haemost. On May 31st, 2021, we received additional information from authors on this study. This study was updated with data from contact with authors on May 31st, 2021. |