Therapeutic Anticoagulation Strategy for Acute Chest Syndrome

Study Overview
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Brief Summary
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Acute Chest Syndrome (ACS) is a pulmonary complication of sickle cell disease (SCD) representing the leading cause of death and the second cause of hospitalization among adult patients. Pulmonary vaso-occlusion is one of the main pathophysiologic hypotheses during ACS. Our hypothesis is that therapeutic anticoagulation may reduce the severity of ACS via the alleviation of pulmonary thrombosis. The main objective of this prospective, randomized, double-blind study is to test the efficacy and safety of a curative anticoagulation strategy during ACS. The main efficacy endpoint is time to ACS resolution. The main safety endpoint is number of major bleedings. A thoracic CT scan will be performed to check for pulmonary artery thrombosis. If the CT scan is positive (thrombosis within a large elastic artery), the patient will not be randomized and will be treated with a curative anticoagulation. If the CT scan is negative, the patient will be randomized to receive subcutaneous anticoagulation with low molecular weight heparin (tinzaparin) either at a curative dose (175 Unit International (UI)/kg/day for 7 days) or at a prophylactic dose (4500 UI/day).

Official Title
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A Prospective, Randomized, Double-blind, Placebo Controlled, Multi-national Study of Therapeutic Anticoagulation Strategy for Acute Chest Syndrome in Adults

Conditions
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Anemia, Sickle Cell, Acute Chest Syndrome, Low-Molecular-Weight Heparin

Intervention / Treatment
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* Drug: Prophylactic anticoagulation ( INNOHEP®)
* Drug: Curative anticoagulation ( INNOHEP®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Major sickle cell syndrome (SS, SC, Sβ) ACS defined by the association of a new infiltrate on chest X-ray or CT scan and a respiratory symptom or abnormal chest auscultation Written, informed consent Main Exclusion Criteria: Pregnancy, post-partum Iodine allergy Extreme weight (<40 kg or > 100 kg) Moderate to severe renal insufficiency Moya-moya disease Symptomatic cerebral aneurysm Major transfusional risk Uncontrolled severe retinopathy All other contra-indications to curative anti-coagulation by tinzaparin.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Prophylactic anticoagulation<br> | Drug: Prophylactic anticoagulation ( INNOHEP®)<br>* subcutaneous anticoagulation with low molecular weight heparin (tinzaparin) at a prophylactic dose (4500 UI/day)<br>|
| Experimental: Curative anticoagulation<br> | Drug: Curative anticoagulation ( INNOHEP®)<br>* subcutaneous anticoagulation with low molecular weight heparin (tinzaparin) at a curative dose (175 UI/kg/day for 7 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The main efficacy endpoint is time to ACS resolution | The delay between randomization and ACS resolution | up to 15 days | 
| Number of major bleedings |  | up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of complicated ACS |  | up to 15 days | 
| Blood volume exchanged |  | up to 15 days | 
| Cumulative dose of opioids |  | up to 15 days | 
| Hospital mortality |  | up to 15 days | 
| Duration of hospital stay |  | up to 15 days | 
| Number of non-major bleedings |  | up to 15 days | 
| Number of readmissions and thromboembolic events within 6 months |  | at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle cell disease, Anemia, Rare disease, Reanimation, Prophylactic anticoagulation