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

Assistance Publique - Hôpitaux de Paris808 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

808

Conditions

COVID19 Pneumonia

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (3)

Réanimation hôpital Louis Mourier

Colombes, Hauts De Seine, France

réanimation hôpital Cochin

Paris, France

Médecine vasculaire, Hôpital Européen Georges Pompidou

Paris, France

Outcomes

Primary Outcomes

Survival without ventilation (VNI or mechanical ventilation)

group 1

Time frame: day 14

ventilator free survival

group 2

Time frame: day 28

Secondary Outcomes

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

Time frame: day 4

World Health Organisation(WHO) progression scale

range from 0 (healthy) to 10 (death)

Time frame: day 4, 7 and 14

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 acute kidney injury

according to Acute Kidney Injury (AKIN) classification system

Time frame: day 28

time to Renal Replacement Therapy (RRT) initiation

Time frame: day 28

rate of clinically overt pulmonary embolism or proximal deep vein thrombosis

confirmed by objective testing

Time frame: day 14 and day 90

Rate of clinically overt arterial thrombosis

confirmed by objective testing

Time frame: day 14 and day 90

Rate of unscheduled central venous catheter replacement for catheter dysfunction

Time frame: 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

Time frame: day 28

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, AOT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system

Time frame: 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

Time frame: day 28

Incidence of adverse events

Time frame: day 28

Central Contacts

Tristan Mirault

CONTACT

1 56 09 50 41 tristan.mirault@aphp.fr

Jean-Luc Diehl

CONTACT

jean-luc.diehl@aphp.fr