Lasky 2021.

Study name	A phase 2/3 study to evaluate the safety and eficacy of dociparstat sodium for the treatment of severe COVID‐19 in adults at high risk of respiratory failure
Starting date	3 June 2020
Contact information	Marion Morrison, MD University of Alabama at Birmingham Birmingham, Alabama, USA, 35294 919‐313‐2977 | mmorrison@chimerix.com
Methods	Double‐blind, 2‐armed, 2:1 parallel‐assignment RCT
Participants	525 participants, ≥ 18 years, female and male Inclusion criteria: Hospitalised for laboratory‐documented COVID‐19 disease (e.g. positive for SARS‐CoV‐2 via nasopharyngeal swab RT‐PCR (or other commercial or public health assay)) Age ≥ 18 years and ≤ 85 years Resting SaO2 of < 94% while breathing ambient air Score of 3 or 4 on the NIAID ordinal scale (requires supplemental oxygen or noninvasive ventilation) Provide informed consent to participate in the study (by participant or legally‐acceptable representative) Exclusion criteria: Currently receiving invasive mechanical ventilation (e.g. via an endotracheal tube) (score of 2 on NIAID ordinal scale) Active or uncontrolled bleeding at the time of randomisation; a bleeding disorder, either inherited or caused by disease; history of known arterial‐venous malformation, intracranial haemorrhage, or suspected or known cerebral aneurysm; or clinically significant (in the judgment of the investigator) gastrointestinal bleeding within the 3 weeks prior to randomisation Receiving any other investigational (non‐approved) therapy for the treatment of COVID‐19 or participating in the treatment period of any other therapeutic invention clinical study Receiving systemic corticosteroids for a chronic condition Receiving chronic anticoagulation with warfarin or DOACs (e.g. rivaroxaban, dabigatran, apixaban, edoxaban) Receiving or anticipated to require other systemic anticoagulation dosing at a therapeutic intensity. Prophylaxis of VTE using SC UFH or enoxaparin is permitted with appropriate monitoring of coagulation status and within guidelines provided in the protocol Receiving antiplatelet therapy, alone or in combination, including aspirin and other antiplatelet agents (e.g. clopidogrel, ticagrelor, and prasugrel), unless able to discontinue these agents at the time of randomisation and to remain off these agents throughout the duration of the study intervention infusion period Treatment with systemic (nonsteroid) immunomodulators or immunosuppressant medications, including but not limited to TNF inhibitors, anti‐interleukin‐1 agents, and Janus kinase (JAK) inhibitors within 5 half‐lives or 30 days (whichever is longer) prior to randomisation Severe chronic liver disease Severe renal impairment QTc > 500 msec (or > 530‐550 msec in patients with QRS > 120 msec) ALT or AST > 5 x ULN aPTT > 42 s Thrombocytopenia with a platelet count < 80,000/mm³ Evidence of clinical improvement in COVID‐19 status including, but not limited to, a sustained reduction in oxygen requirements over the previous 48 h, or extubated and/or no longer requiring mechanical ventilation following intubation for COVID‐19 Any other condition, including abnormal laboratory values, that, in the judgment of the investigator, could put the participant at increased risk, or would interfere with the conduct or planned analysis of the study
Interventions	Experimental: dociparstat sodium (DSTAT) Dociparstat 4 mg/kg IV bolus on day 1, followed by dociparstat by continuous IV infusion for 24 h daily for 7 days (starting on day 1 and ending on day 8 (168 h)) Dociparstat is a glycosaminoglycan derived from porcine heparin Comparator: placebo Placebo IV bolus on day 1, followed by placebo by continuous IV infusion for 24 h daily for 7 days (starting on day 1 and ending on day 8 (168 h)) 0.9% normal saline
Outcomes	Primary Proportion of participants who are alive and free of invasive mechanical ventilation (time frame: through day 28) Alive and free of invasive mechanical ventilation Secondary All‐cause mortality (time frame: through day 28) Time to all‐cause mortality
Notes	NCT04389840 | No data provided