Therapeutic Anticoagulation Strategy for Acute Chest Syndrome

NCT02580773 | Completed Phase 3 DMC

• 1 other identifier: AOR14068
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 1

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).

Conditions

Anemia; Sickle Cell; Acute Chest Syndrome; Low-Molecular-Weight Heparin

Keywords

Sickle cell disease; Anemia; Rare disease; Reanimation; Prophylactic anticoagulation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• 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

Study Arms (2)

Prophylactic anticoagulation

OTHER

Drug: Prophylactic anticoagulation ( INNOHEP®)

Curative anticoagulation

EXPERIMENTAL

Drug: Curative anticoagulation ( INNOHEP®)

Interventions

Prophylactic anticoagulation ( INNOHEP®) DRUG

subcutaneous anticoagulation with low molecular weight heparin (tinzaparin) at a prophylactic dose (4500 UI/day)

Prophylactic anticoagulation

Curative anticoagulation ( INNOHEP®) DRUG

subcutaneous anticoagulation with low molecular weight heparin (tinzaparin) at a curative dose (175 UI/kg/day for 7 days)

Curative anticoagulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• LEO Pharma: collaborator

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

Location

Related Publications (3)

• 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.

  PMID: 17721622 BACKGROUND

• 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.

  PMID: 21836136 BACKGROUND

• Mekontso Dessap A, Habibi A, Arlet JB, Fartoukh M, Guerin L, Guillaud C, Roux D, Oziel J, Ngo S, Carpentier B, Lopez-Sublet M, Affo L, Melica G, Etienne-Julan M, Delacroix I, Lionnet F, Loko G, Da Silva D, Michel M, Razazi K, Charles-Nelson A, Bartolucci P, Gendreau S, Katsahian S, Maitre B. Comparison of Prophylactic and Therapeutic Doses of Anticoagulation for Acute Chest Syndrome in Sickle Cell Disease: The TASC Double-Blind Controlled Randomized Clinical Trial. Am J Respir Crit Care Med. 2025 May;211(5):832-841. doi: 10.1164/rccm.202409-1727OC.

  PMID: 40209087 DERIVED

MeSH Terms

Conditions

Anemia; Acute Chest Syndrome; Anemia, Sickle Cell; Rare Diseases

Interventions

Tinzaparin

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Bernard Maitre, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Armand Mekontso Dessap, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2015
• First Posted: October 20, 2015
• Study Start: December 16, 2016
• Primary Completion: February 4, 2021
• Study Completion: September 15, 2021
• Last Updated: February 9, 2024

Record last verified: 2020-04

Locations

FR (1)