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COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent Covid-19 or infection with SARS-CoV-2 or therapeutic agent to treat COVID-19.
This protocol CORIMUNO19-COAG will evaluate the efficacy and safety of active anticoagulation using heparin: Tinzaparin (INNOHEP®) or unfractionated heparin (Calciparine®, Héparine Sodique Choay®) in COVID-19 patients hospitalized in conventional or intensive care units.
It will use a phase 2 randomized open-label multicentre clinical trial, where patients will be randomly allocated to anticoagulation versus Standard of Care.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Coagulation | Experimental |
| |
| Standard of Care | No Intervention | Control patients will receive the best standard of care and a subcutaneous preventive anticoagulation for at least 14 days with enoxaparin 4000 IU/24h, tinzaparin 3500 IU/24h or dalteparin 5000 IU/24h if creatinine clearance (Cockcroft) ≥ 30mL/min or unfractionated heparin 5000 IU/12h if creatinine clearance < 30mL/min. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tinzaparin or unfractionated heparin | Drug | Tinzaparin INNOHEP ® 175 IU/kg/24h for 14 days if creatinine clearance Cockcroft ≥ 20mL/min, Otherwise unfractionated heparin (Calciparine®, Héparine Sodique Choay®) subcutaneously or intravenous with an anti-Xa target between 0.5 and 0.7 IU/mL for 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Survival without ventilation (VNI or mechanical ventilation) | group 1 | day 14 |
| ventilator free survival | group 2 | day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| World Health Organisation(WHO) progression scale ≤5 | range from 0 (healthy) to 10 (death) values below or equal to 5 correspond to the absence of any oxygen supply beside nasal or facial mask | day 4 |
| World Health Organisation(WHO) progression scale |
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Inclusion Criteria:
group 1 : patients not requiring ICU at admission with mild disease to severe pneumopathy according to The Who Criteria of severity of COVID pneumopathy, and with symptom onset before 14 days, with need for oxygen but No non-invasive ventilation (NIV) or High flow
group 2 :
Exclusion Criteria:
Patients with contraindications to anticoagulation
Patients with need for anticoagulant therapy. For example: atrial fibrillation, venous thromboembolism, mechanical valve, etc.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tristan Mirault | Contact | 1 56 09 50 41 | 33 | tristan.mirault@aphp.fr |
| Jean-Luc Diehl | Contact | jean-luc.diehl@aphp.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Réanimation hôpital Louis Mourier | Colombes | Hauts De Seine | 92701 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35244208 | Derived | Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2. | |
| 33502773 | Derived | Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739. |
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Randomized clinical trial with 2 parallels arms, 1:1, stratified on disease severity (ventilation or not)
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|
range from 0 (healthy) to 10 (death)
| day 4, 7 and 14 |
| overall survival | day 14, 28 and 90 |
| Length of hospital stay | day 28 |
| Length of ICU stay | day 28 |
| time to oxygenation supply independency | day 28 |
| time to ventilator (non invasive or invasive) | day 28 |
| rate of acute kidney injury | according to Acute Kidney Injury (AKIN) classification system | day 28 |
| time to Renal Replacement Therapy (RRT) initiation | day 28 |
| rate of clinically overt pulmonary embolism or proximal deep vein thrombosis | confirmed by objective testing | day 14 and day 90 |
| Rate of clinically overt arterial thrombosis | confirmed by objective testing | day 14 and day 90 |
| Rate of unscheduled central venous catheter replacement for catheter dysfunction | day 28 |
| Rate of central venous catheter-related deep vein thrombosis (CVC-DVT) | 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 pulmonary embolism or compulsory catheter removal | day 28 |
| Rate of unscheduled indwelling arterial catheter replacement for catheter dysfunction | day 28 |
| Rate of acute clotting leading to the replacement the renal replacement therapy circuit stratified by regional citrate anticoagulation or not | day 28 |
| Time to acute clot formation within the oxygenator (acute oxygenator thrombosis, AOT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system | day 28 |
| Time to acute clot formation within the pump head (pump head thrombosis, PHT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system | day 28 |
| Incidence of adverse events | day 28 |
| réanimation hôpital Cochin | Paris | 75014 | France |
|
| Médecine vasculaire, Hôpital Européen Georges Pompidou | Paris | 75015 | France |
| ID | Term |
|---|---|
| D000078222 | Tinzaparin |
| D006493 | Heparin |
| ID | Term |
|---|---|
| D006495 | Heparin, Low-Molecular-Weight |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
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