Trial Evaluating Efficacy and Safety of Anticoagulation in Patients With COVID-19 Infection, Nested in the Corimmuno-19 Cohort (CORIMMUNO-COAG)

• ClinicalTrials.gov Identifier: NCT04344756
• Recruitment Status: Not yet recruiting
• First Posted: April 14, 2020
• Last Update Posted: April 15, 2020
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID19 Pneumonia	Drug: Tinzaparin or unfractionated heparin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 808 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized clinical trial with 2 parallels arms, 1:1, stratified on disease severity (ventilation or not)
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients CORIMUNO-COAG Trial
• Estimated Study Start Date: April 20, 2020
• Estimated Primary Completion Date: July 31, 2020
• Estimated Study Completion Date: September 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active Coagulation	Drug: Tinzaparin or unfractionated heparin; 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
No Intervention: Standard of Care; 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.

Outcome Measures

Primary Outcome Measures :

1. Survival without ventilation (VNI or mechanical ventilation) [ Time Frame: day 14 ]
   group 1
2. ventilator free survival [ Time Frame: day 28 ]
   group 2

Secondary Outcome Measures :

1. World Health Organisation(WHO) progression scale ≤5 [ Time Frame: day 4 ]
   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
2. World Health Organisation(WHO) progression scale [ Time Frame: day 4, 7 and 14 ]
   range from 0 (healthy) to 10 (death)
3. overall survival [ Time Frame: day 14, 28 and 90 ]
4. Length of hospital stay [ Time Frame: day 28 ]
5. Length of ICU stay [ Time Frame: day 28 ]
6. time to oxygenation supply independency [ Time Frame: day 28 ]
7. time to ventilator (non invasive or invasive) [ Time Frame: day 28 ]
8. rate of acute kidney injury [ Time Frame: day 28 ]
   according to Acute Kidney Injury (AKIN) classification system
9. time to Renal Replacement Therapy (RRT) initiation [ Time Frame: day 28 ]
10. rate of clinically overt pulmonary embolism or proximal deep vein thrombosis [ Time Frame: day 14 and day 90 ]
    confirmed by objective testing
11. Rate of clinically overt arterial thrombosis [ Time Frame: day 14 and day 90 ]
    confirmed by objective testing
12. Rate of unscheduled central venous catheter replacement for catheter dysfunction [ Time Frame: day 28 ]
13. Rate of central venous catheter-related deep vein thrombosis (CVC-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 pulmonary embolism or compulsory catheter removal
14. Rate of unscheduled indwelling arterial catheter replacement for catheter dysfunction [ Time Frame: day 28 ]
15. Rate of acute clotting leading to the replacement the renal replacement therapy circuit stratified by regional citrate anticoagulation or not [ Time Frame: day 28 ]
16. Time to acute clot formation within the oxygenator (acute oxygenator thrombosis, AOT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system [ Time Frame: day 28 ]
17. Time to acute clot formation within the pump head (pump head thrombosis, PHT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system [ Time Frame: day 28 ]
18. Incidence of adverse events [ Time Frame: day 28 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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

2. group 2 :

   • Respiratory failure AND requiring mechanical ventilation
   • WHO progression scale ≥ 6
   • No do-not-resuscitate order (DNR order)

Exclusion Criteria:

• Patients with contraindications to anticoagulation

  1. Congenital hemorrhagic disorders
  2. Hypersensitivity to tinzaparin or UHF or to any of the excipients
  3. Current or history of immune-mediated heparin-induced thrombocytopenia
  4. Active major haemorrhage or conditions predisposing to major haemorrhage. Major haemorrhage is defined as fulfilling any one of these three criteria: a) occurs in a critical area or organ (e.g. intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, intra-uterine or intramuscular with compartment syndrome), b) causes a fall in haemoglobin level of 20 g/L (1.24 mmol/L) or more, or c) leads to transfusion of 2 or more units of whole blood or red blood cells.
  5. Septic endocarditis
• Patients with need for anticoagulant therapy. For example: atrial fibrillation, venous thromboembolism, mechanical valve, etc.

Contacts and Locations

Contacts

Contact: Tristan Mirault; 1 56 09 50 41 ext 33; tristan.mirault@aphp.fr

Contact: Jean-Luc Diehl; jean-luc.diehl@aphp.fr

Locations

France

Réanimation hôpital Louis Mourier

Colombes, Hauts De Seine, France, 92701

Contact: Damien Roux, MD PhD 1 47 60 61 62 ext 33 damien.roux@aphp.fr

réanimation hôpital Cochin

Paris, France, 75014

Contact: Frédéric Penne, MD PhD 1 58 41 25 27 ext 33

Médecine vasculaire, Hôpital Européen Georges Pompidou

Paris, France, 75015

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT04344756
• Other Study ID Numbers: APHP200389-6
• First Posted: April 14, 2020
• Last Update Posted: April 15, 2020
• Last Verified: April 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Heparin; Calcium heparin; Tinzaparin; Heparin, Low-Molecular-Weight; Dalteparin; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action