Covid-19 Living Data

Trial NCT04486508
Publication INSPIRATION - 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 Intermediate dose Enoxaparin: 1 mg/kg once daily for 30 days (if weight < 120kg and creatinine clearance > 30 ml/min).
	Control Standard dose 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).
Participants
	Randomized participants : Standard dose=299 Intermediate dose=299
	Characteristics of participants N= 598 Mean age : NR 325 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=449 Critical: n=113 Number of vaccinated participants: NR
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 willing stated in the publication: 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.