Therapeutic Anticoagulation Strategy for Acute Chest Syndrome (TASC)

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

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).

Study Overview

• Status: Completed
• Conditions: Anemia; Acute Chest Syndrome; Sickle Cell; Low-Molecular-Weight Heparin
• Intervention / Treatment: Drug: Prophylactic anticoagulation ( INNOHEP®); Drug: Curative anticoagulation ( INNOHEP®)

• Study Type: Interventional
• Enrollment (Actual): 198
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Armand Mekontso Dessap, MD, PhD; Phone Number: +33 (0)149812394; Email: armand.dessap@aphp.fr

Study Locations

• France
  • Creteil, France, 94010
    • Henri Mondor Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: LEO Pharma
• Investigators: Study Chair: Armand Mekontso Dessap, MD, PhD, Assistance Publique - Hôpitaux de Paris; Principal Investigator: Bernard Maitre, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2016
• Primary Completion (Actual): February 4, 2021
• Study Completion (Actual): September 15, 2021

Study Registration Dates

• First Submitted: October 5, 2015
• First Submitted That Met QC Criteria: October 18, 2015
• First Posted (Estimated): October 20, 2015

Study Record Updates

• Last Update Posted (Actual): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Anemia; Sickle cell disease; Rare disease; Reanimation; Prophylactic anticoagulation
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Syndrome; Acute Chest Syndrome; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Tinzaparin
• Other Study ID Numbers: AOR14068

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No