Clinical trial NCT02580773: Therapeutic Anticoagulation Strategy for Acute Chest Syndrome
Official title: A Prospective, Randomized, Double-blind, Placebo Controlled, Multi-national Study of Therapeutic Anticoagulation Strategy for Acute Chest Syndrome in Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
Sickle Cell
Acute Chest Syndrome
Low-Molecular-Weight Heparin
Keywords: Sickle cell disease
Anemia
Rare disease
Reanimation
Prophylactic anticoagulation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: LEO Pharma
First posted: 2015-10-20
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: The main efficacy endpoint is time to ACS resolution
timeFrame: up to 15 days
measure: Number of major bleedings
timeFrame: up to 15 days
Secondary outcomes:
measure: Number of complicated ACS
timeFrame: up to 15 days
measure: Blood volume exchanged
timeFrame: up to 15 days
measure: Cumulative dose of opioids
timeFrame: up to 15 days
measure: Hospital mortality
timeFrame: up to 15 days
measure: Duration of hospital stay
timeFrame: up to 15 days
measure: Number of non-major bleedings
timeFrame: up to 15 days
measure: Number of readmissions and thromboembolic events within 6 months
timeFrame: at 6 months
Other outcomes:
Locations:
city: Creteil
country: France
facility: Henri Mondor Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Bernard Maitre, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Armand Mekontso Dessap, MD, PhD
role: STUDY_CHAIR
References:
citation: Qari MH, Aljaouni SK, Alardawi MS, Fatani H, Alsayes FM, Zografos P, Alsaigh M, Alalfi A, Alamin M, Gadi A, Mousa SA. Reduction of painful vaso-occlusive crisis of sickle cell anaemia by tinzaparin in a double-blind randomized trial. Thromb Haemost. 2007 Aug;98(2):392-6.
citation: Mekontso Dessap A, Deux JF, Abidi N, Lavenu-Bombled C, Melica G, Renaud B, Godeau B, Adnot S, Brochard L, Brun-Buisson C, Galacteros F, Rahmouni A, Habibi A, Maitre B. Pulmonary artery thrombosis during acute chest syndrome in sickle cell disease. Am J Respir Crit Care Med. 2011 Nov 1;184(9):1022-9. doi: 10.1164/rccm.201105-0783OC.