Back to resultsTrial Evaluating Efficacy and Safety of Anticoagulation in Patients With COVID-19 Infection, Nested in the Corimmuno-19 Cohort (CORIMMUNO-COAG)
Primary Purpose
COVID19 Pneumonia
Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Tinzaparin or unfractionated heparin
Sponsored by
About this trial
This is an interventional treatment trial for COVID19 Pneumonia
Eligibility Criteria
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 :
- Respiratory failure AND requiring mechanical ventilation
- WHO progression scale ≥ 6
- No do-not-resuscitate order (DNR order)
Exclusion Criteria:
Patients with contraindications to anticoagulation
- Congenital hemorrhagic disorders
- Hypersensitivity to tinzaparin or UHF or to any of the excipients
- Current or history of immune-mediated heparin-induced thrombocytopenia
- 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.
- Septic endocarditis
- Patients with need for anticoagulant therapy. For example: atrial fibrillation, venous thromboembolism, mechanical valve, etc.
Sites / Locations
- Réanimation hôpital Louis Mourier
- réanimation hôpital Cochin
- Médecine vasculaire, Hôpital Européen Georges Pompidou
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Active Coagulation
Standard of Care
Arm Description
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.
Outcomes
Primary Outcome Measures
Survival without ventilation (VNI or mechanical ventilation)
group 1
ventilator free survival
group 2
Secondary Outcome Measures
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
World Health Organisation(WHO) progression scale
range from 0 (healthy) to 10 (death)
overall survival
Length of hospital stay
Length of ICU stay
time to oxygenation supply independency
time to ventilator (non invasive or invasive)
rate of acute kidney injury
according to Acute Kidney Injury (AKIN) classification system
time to Renal Replacement Therapy (RRT) initiation
rate of clinically overt pulmonary embolism or proximal deep vein thrombosis
confirmed by objective testing
Rate of clinically overt arterial thrombosis
confirmed by objective testing
Rate of unscheduled central venous catheter replacement for catheter dysfunction
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
Rate of unscheduled indwelling arterial catheter replacement for catheter dysfunction
Rate of acute clotting leading to the replacement the renal replacement therapy circuit stratified by regional citrate anticoagulation or not
Time to acute clot formation within the oxygenator (acute oxygenator thrombosis, AOT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system
Time to acute clot formation within the pump head (pump head thrombosis, PHT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system
Incidence of adverse events
Full Information
NCT ID
NCT04344756
First Posted
April 9, 2020
Last Updated
April 14, 2020
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT04344756
Brief Title
Trial Evaluating Efficacy and Safety of Anticoagulation in Patients With COVID-19 Infection, Nested in the Corimmuno-19 Cohort
Acronym
CORIMMUNO-COAG
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
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 20, 2020 (Anticipated)
Primary Completion Date
July 31, 2020 (Anticipated)
Study Completion Date
September 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID19 Pneumonia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized clinical trial with 2 parallels arms, 1:1, stratified on disease severity (ventilation or not)
Masking
None (Open Label)
Allocation
Randomized
Enrollment
808 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active Coagulation
Arm Type
Experimental
Arm Title
Standard of Care
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tinzaparin or unfractionated heparin
Intervention Description
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
Primary Outcome Measure Information:
Title
Survival without ventilation (VNI or mechanical ventilation)
Description
group 1
Time Frame
day 14
Title
ventilator free survival
Description
group 2
Time Frame
day 28
Secondary Outcome Measure Information:
Title
World Health Organisation(WHO) progression scale ≤5
Description
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
Title
World Health Organisation(WHO) progression scale
Description
range from 0 (healthy) to 10 (death)
Time Frame
day 4, 7 and 14
Title
overall survival
Time Frame
day 14, 28 and 90
Title
Length of hospital stay
Time Frame
day 28
Title
Length of ICU stay
Time Frame
day 28
Title
time to oxygenation supply independency
Time Frame
day 28
Title
time to ventilator (non invasive or invasive)
Time Frame
day 28
Title
rate of acute kidney injury
Description
according to Acute Kidney Injury (AKIN) classification system
Time Frame
day 28
Title
time to Renal Replacement Therapy (RRT) initiation
Time Frame
day 28
Title
rate of clinically overt pulmonary embolism or proximal deep vein thrombosis
Description
confirmed by objective testing
Time Frame
day 14 and day 90
Title
Rate of clinically overt arterial thrombosis
Description
confirmed by objective testing
Time Frame
day 14 and day 90
Title
Rate of unscheduled central venous catheter replacement for catheter dysfunction
Time Frame
day 28
Title
Rate of central venous catheter-related deep vein thrombosis (CVC-DVT)
Description
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
Title
Rate of unscheduled indwelling arterial catheter replacement for catheter dysfunction
Time Frame
day 28
Title
Rate of acute clotting leading to the replacement the renal replacement therapy circuit stratified by regional citrate anticoagulation or not
Time Frame
day 28
Title
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
Title
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
Title
Incidence of adverse events
Time Frame
day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 :
Respiratory failure AND requiring mechanical ventilation
WHO progression scale ≥ 6
No do-not-resuscitate order (DNR order)
Exclusion Criteria:
Patients with contraindications to anticoagulation
Congenital hemorrhagic disorders
Hypersensitivity to tinzaparin or UHF or to any of the excipients
Current or history of immune-mediated heparin-induced thrombocytopenia
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.
Septic endocarditis
Patients with need for anticoagulant therapy. For example: atrial fibrillation, venous thromboembolism, mechanical valve, etc.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tristan Mirault
Phone
1 56 09 50 41
Ext
33
Email
tristan.mirault@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Jean-Luc Diehl
Email
jean-luc.diehl@aphp.fr
Facility Information:
Facility Name
Réanimation hôpital Louis Mourier
City
Colombes
State/Province
Hauts De Seine
ZIP/Postal Code
92701
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Damien Roux, MD PhD
Phone
1 47 60 61 62
Ext
33
Email
damien.roux@aphp.fr
Facility Name
réanimation hôpital Cochin
City
Paris
ZIP/Postal Code
75014
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frédéric Penne, MD PhD
Phone
1 58 41 25 27
Ext
33
Facility Name
Médecine vasculaire, Hôpital Européen Georges Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
35244208
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.
Results Reference
derived
PubMed Identifier
33502773
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.
Results Reference
derived
Learn more about this trial
Trial Evaluating Efficacy and Safety of Anticoagulation in Patients With COVID-19 Infection, Nested in the Corimmuno-19 Cohort
We'll reach out to this number within 24 hrs