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

• ClinicalTrials.gov Identifier: NCT02966119
• Recruitment Status: Terminated
• First Posted: November 17, 2016
• Last Update Posted: May 9, 2022
• Sponsor: University Hospital, Lille
• Collaborators: Région Hauts de France, France; Ministry of Health, France
• Information provided by (Responsible Party): University Hospital, Lille

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cerebral Hemorrhage	Drug: Clopidogrel or Aspirin and/or Dypyridamole	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: December 7, 2016
• Actual Primary Completion Date: December 7, 2019
• Actual Study Completion Date: December 7, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

France

Hôpital Roger Salengro, CHRU de Lille

Lille, France

Sponsors and Collaborators

University Hospital, Lille

Région Hauts de France, France

Ministry of Health, France

Investigators

• Principal Investigator: Charlotte CORDONNIER, MD, PhD; University Hospital, Lille

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University Hospital, Lille
• ClinicalTrials.gov Identifier: NCT02966119
• Other Study ID Numbers: 2015_11; 2015-A01319-40 ( Other Identifier: ID-RCB number, ANSM ); PHRCI_2014 ( Other Identifier: PHRC number, DGOS )
• First Posted: November 17, 2016
• Last Update Posted: May 9, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: we plan to make IPD analysis with sister trial: RESTART UK

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Lille:

stroke; intracranial hemorrhage; intracerebral hemorrhage; antithrombotic drugs; brain microbleeds

Additional relevant MeSH terms:

Cerebral Hemorrhage; Hemorrhage; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Aspirin; Clopidogrel; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists