NCT04344756.

Study name	Cohort multiple randomized controlled trials open‐label of immune modulatory drugs and other treatments in COVID‐19 patients CORIMUNO‐COAG trial
Starting date	20 April 2020
Contact information	Tristan Mirault Assistance Publique ‐ Hôpitaux de Paris, France 1 56 09 50 41 ext 33 | tristan.mirault@aphp.fr
Methods	Randomised clinical trial with 2 parallel arms, 1:1, stratified on disease severity (ventilation or not)
Participants	808 participants, ≥ 18 years, female and male Inclusion criteria group 1: participants not requiring ICU at admission with mild disease to severe pneumopathy according to the WHO criteria of severity of COVID‐19 pneumopathy, and with symptom onset before 14 days, with need for oxygen but no NIV or high flow group 2 : respiratory failure AND requiring mechanical ventilation WHO progression scale ≥ 6 no do‐not‐resuscitate order Exclusion criteria Participants with contraindications to anticoagulation Congenital hemorrhagic disorders Hypersensitivity to tinzaparin or UHF or to any of the excipients Current or history of immune‐mediated HIT Active major haemorrhage or conditions predisposing to major haemorrhage. Major haemorrhage is defined as fulfilling any one of these 3 criteria: occurs in a critical area or organ (e.g. intracranial, intraspinal, intraocular, retroperitoneal, intra‐articular or pericardial, intra‐uterine or intramuscular with compartment syndrome) causes a fall in haemoglobin level of ≥ 20 g/L (1.24 mmol/L) leads to transfusion of ≥ 2 units of whole blood or red blood cells Septic endocarditis Participants with need for anticoagulant therapy, e.g. atrial fibrillation, VTE, mechanical valve, etc
Interventions	Experimental: tinzaparin or UFH Tinzaparin INNOHEP 175 IU/kg/24 h for 14 days if creatinine clearance Cockcroft ≥ 20 mL/min, otherwise UFH (Calciparine, Héparine Sodique Choay) SC or IV with an anti‐Xa target between 0.5 and 0.7 IU/mL for 14 days Comparator: standard of care Control participants will receive the best standard of care and a SC preventive anticoagulation for at least 14 days with enoxaparin 4000 IU/24 h, tinzaparin 3500 IU/24 h or dalteparin 5000 IU/24 h if creatinine clearance (Cockcroft) ≥ 30 mL/min or UFH 5000 IU/12 h if creatinine clearance < 30 mL/min
Outcomes	Primary Survival without ventilation (NIV or mechanical ventilation) (time frame: day 14) group 1 ventilator‐free survival (time frame: day 28) group 2 Secondary WHO progression scale ≤ 5 (time frame: day 4) range from 0 (healthy) to 10 (death) values ≤ 5 correspond to the absence of any oxygen supply beside nasal or facial mask WHO progression scale (time frame: day 4, 7 and 14) range from 0 (healthy) to 10 (death) overall survival (time frame: day 14, 28 and 90) Length of hospital stay (time frame: day 28) Length of ICU stay (time frame: day 28) Time to oxygenation supply independency (time frame: day 28) Time to ventilator (non‐invasive or invasive) (time frame: day 28) Rate of AKI (time frame: day 28) according to Acute Kidney Injury classification system Time to renal replacement therapy initiation (time frame: day 28) Rate of clinically overt PE or proximal DVT (time frame: day 14 and day 90) confirmed by objective testing Rate of clinically overt arterial thrombosis (time frame: day 14 and day 90) confirmed by objective testing Rate of unscheduled central venous catheter replacement for catheter dysfunction (time frame: day 28) Rate of central venous catheter‐related DVT (time frame: day 28) as a thrombus extending from the catheter into the lumen of the deep vein where the catheter is inserted diagnosed with radiologic imaging in case of a clinical suspicion of upper/lower limb DVT or PE or compulsory catheter removal Rate of unscheduled indwelling arterial catheter replacement for catheter dysfunction (time frame: day 28) Rate of acute clotting leading to the replacement the renal replacement therapy circuit stratified by regional citrate anticoagulation or not (time frame: day 28) Time to acute clot formation within the oxygenator (acute oxygenator thrombosis) leading to the exchange of an ECMO system (time frame: day 28) Time to acute clot formation within the pump head (pump head thrombosis) leading to the exchange of an ECMO system (time frame: day 28) Incidence of adverse events (time frame: day 28)
Notes	NCT04344756 | APHP200389‐6 | No data provided