Clinical trial NCT04344756: Trial Evaluating Efficacy and Safety of Anticoagulation in Patients With COVID-19 Infection, Nested in the Corimmuno-19 Cohort
Official title: Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients CORIMUNO-COAG Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID19 Pneumonia
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-04-14
Enrollment: 808
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized clinical trial with 2 parallels arms, 1:1, stratified on disease severity (ventilation or not)
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Survival without ventilation (VNI or mechanical ventilation)
timeFrame: day 14
measure: ventilator free survival
timeFrame: day 28
Secondary outcomes:
measure: World Health Organisation(WHO) progression scale ≤5
timeFrame: day 4
measure: World Health Organisation(WHO) progression scale
timeFrame: day 4, 7 and 14
measure: overall survival
timeFrame: day 14, 28 and 90
measure: Length of hospital stay
timeFrame: day 28
measure: Length of ICU stay
timeFrame: day 28
measure: time to oxygenation supply independency
timeFrame: day 28
measure: time to ventilator (non invasive or invasive)
timeFrame: day 28
measure: rate of acute kidney injury
timeFrame: day 28
measure: time to Renal Replacement Therapy (RRT) initiation
timeFrame: day 28
measure: rate of clinically overt pulmonary embolism or proximal deep vein thrombosis
timeFrame: day 14 and day 90
measure: Rate of clinically overt arterial thrombosis
timeFrame: day 14 and day 90
measure: Rate of unscheduled central venous catheter replacement for catheter dysfunction
timeFrame: day 28
measure: Rate of central venous catheter-related deep vein thrombosis (CVC-DVT)
timeFrame: day 28
measure: Rate of unscheduled indwelling arterial catheter replacement for catheter dysfunction
timeFrame: day 28
measure: Rate of acute clotting leading to the replacement the renal replacement therapy circuit stratified by regional citrate anticoagulation or not
timeFrame: day 28
measure: Time to acute clot formation within the oxygenator (acute oxygenator thrombosis, AOT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system
timeFrame: day 28
measure: Time to acute clot formation within the pump head (pump head thrombosis, PHT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system
timeFrame: day 28
measure: Incidence of adverse events
timeFrame: day 28
Other outcomes:
Locations:
city: Colombes
country: France
facility: Réanimation hôpital Louis Mourier
state: Hauts De Seine
city: Paris
country: France
facility: réanimation hôpital Cochin
city: Paris
country: France
facility: Médecine vasculaire, Hôpital Européen Georges Pompidou
Study officials:
References:
citation: 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.
citation: 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.