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

Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients CORIMUNO-COAG Trial

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.

Study Overview

• Status: Unknown
• Conditions: COVID19 Pneumonia
• Intervention / Treatment: Drug: Tinzaparin or unfractionated heparin

• Study Type: Interventional
• Enrollment (Anticipated): 808
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tristan Mirault; Phone Number: 33 1 56 09 50 41; Email: tristan.mirault@aphp.fr
• Study Contact Backup: Name: Jean-Luc Diehl; Email: jean-luc.diehl@aphp.fr

Study Locations

• France
  • Paris, France, 75014
    • réanimation hôpital Cochin
    • Contact: Frédéric Penne, MD PhD; Phone Number: 33 1 58 41 25 27
  • Paris, France, 75015
    • Médecine vasculaire, Hôpital Européen Georges Pompidou
  • Hauts De Seine
    • Colombes, Hauts De Seine, France, 92701
      • Réanimation hôpital Louis Mourier
      • Contact: Damien Roux, MD PhD; Phone Number: 33 1 47 60 61 62; Email: damien.roux@aphp.fr

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival without ventilation (VNI or mechanical ventilation)	group 1	day 14
ventilator free survival	group 2	day 28

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• 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. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 20, 2020
• Primary Completion (Anticipated): July 31, 2020
• Study Completion (Anticipated): September 30, 2020

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: April 12, 2020
• First Posted (Actual): April 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 15, 2020
• Last Update Submitted That Met QC Criteria: April 14, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: APHP200389-6

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No