REstart or STop Antithrombotic Randomised Trial in France (RESTART-Fr)

Evaluation of the Benefit/Risk Ratio of Restarting or Avoiding Antiplatelet Drugs in Patients Who Had a Spontaneous Intracerebral Hemorrhage While Treated With Antithrombotic Drugs : RESTART-FR Study

RESTART- fr is a randomised controlled trial for adults surviving spontaneous intracerebral haemorrhage who had taken an antithrombotic drug (i.e. anticoagulant or antiplatelet medication) for the prevention of vaso-occlusive disease before the ICH.

RESTART- fr is testing whether a policy of starting antiplatelet drugs (one or more of aspirin, clopidogrel, or dipyridamole, chosen at investigator's discretion) results in a beneficial net reduction of all serious vascular events over two years compared with a policy of avoiding antiplatelet drugs.

Study Overview

• Status: Terminated
• Conditions: Cerebral Hemorrhage
• Intervention / Treatment: Drug: Clopidogrel or Aspirin and/or Dypyridamole

Detailed Description

More than one third of the adults with a stroke due to bleeding into the brain - known as brain haemorrhage - are taking drugs to prevent clotting when they have a brain haemorrhage.

These patients had previously suffered illnesses like angina, heart attack, or stroke due to blood vessel blockage, which is why they are treated with drugs to prevent further clots occurring. These drugs are usually stopped when the brain haemorrhage occurs.

But when patients recover from brain haemorrhage, they and their doctors are often uncertain about whether to restart these drugs to prevent further clots occurring, or whether to avoid them in case they increase the risk of brain haemorrhage happening again.

In this preliminary study of 292 such people who survive a brain haemorrhage, we will study the potentially beneficial effects of three antiplatelet drugs (one or more of aspirin, clopidogrel, or dipyridamole, chosen by the patient's physician) on the risks of heart attack, stroke and other clotting problems as well as their effect on the risk of a brain haemorrhage happening again.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Lille, France
    • Hopital Roger Salengro, CHRU de Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient age ≥18 years.
• Spontaneous intracerebral hemorrhage confirmed by imaging
• Patient had been taken antithrombotic drug(s) for the prevention of vaso-occlusive disease for at least 1 week before ICH onset
• Randomisation more than 24 hours after ICH onset.
• Patient and their doctor are uncertain about whether to start or avoid antiplatelet drugs.
• Brain imaging that first diagnosed the ICH is available. Participant or representative consent.

Exclusion Criteria:

• intracerebral hemorrhage associated with : a vascular malformation (AVM, arterial aneurysm, cavernoma); a secondary hemorrhagic infarction; a cerebral venous thrombosis; a tumor
• Patients with a formal indication of restarting oral anticoagulants despite the ICH (eg mechanical heart valves or pulmonary embolism under 6 months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Start antiplatelet drug(s); If the patient is randomized in this arm, an antiplatelet agent (aspirin or clopidogrel or dypyridamole), chosen by the patient's physician before the randomisation, will be prescribed to the patient during the study period	Drug: Clopidogrel or Aspirin and/or Dypyridamole; The physician will prescribe on this antiplatelet agent if the patient is randomized in the arm " restart"
No Intervention: Avoid antiplatelet drug(s); If the patient is randomized in this arm, antiplatelet drugs will not be prescribed to the patient during the entire study period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with symptomatic intracerebral hemorrhage	Occurrence of a fatal or non-fatal symptomatic ICH proven radiologically at follow-up ( brain CT or MRI) .	at one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serious fatal vascular events (i.e. followed by death within 30 days ) or non- fatal	symptomatic hemorrhagic events, symptomatic ischemic events, stroke of undetermined nature	at one year and at the end of follow-up (2 years)
Other fatal events	Death without pre-defined vascular cause	at one year and at the end of follow-up (2 years)
Rankin Scale	modified Rankin Scale: dichotomized mRS 0-1-2 (no dependency) versus 3 or more (dependency or death)	2 years

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Ministry of Health, France; Région Hauts de France, France
• Investigators: Principal Investigator: Charlotte CORDONNIER, MD, PhD, University Hospital, Lille

Publications and helpful links

General Publications

• Cheng X, Dong Q. Towards individualised secondary prevention after intracerebral haemorrhage. Lancet Neurol. 2021 Jun;20(6):411-413. doi: 10.1016/S1474-4422(21)00130-7. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2016
• Primary Completion (Actual): December 7, 2019
• Study Completion (Actual): December 7, 2019

Study Registration Dates

• First Submitted: July 13, 2016
• First Submitted That Met QC Criteria: November 14, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: stroke; intracerebral hemorrhage; intracranial hemorrhage; antithrombotic drugs; brain microbleeds
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: 2015_11; PHRCI_2014 (Other Identifier: PHRC number, DGOS); 2015-A01319-40 (Other Identifier: ID-RCB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: we plan to make IPD analysis with sister trial: RESTART UK

Drug and device information, study documents

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