Study of Antithrombotic Treatment After IntraCerebral Haemorrhage (STATICH)

The study evaluates the effects of antithrombotic drugs (anticoagulant drugs or antiplatelet drugs) for prevention of ischaemic events in patients With recent intracerebral haemorrhage.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Intracranial Hemorrhages; Cerebral Hemorrhage; Secondary Prevention; Anticoagulant-Induced Bleeding
• Intervention / Treatment: Drug: Antithrombotic Agent

Detailed Description

Patients with spontaneous ICH have an increased risk of recurrent ICH and they also have an increased risk of ischaemic diseases. Around 40-50% of patients use, or have an indication, for antithrombotic drugs at the time of ICH. However, little is known about the benefits and harms of using antithrombotic drugs for prevention of ischaemic events in patients who have had an ICH.

There are only observational studies addressing this question. Because of the lack of randomised-controlled trials and the inconclusive findings of the observational studies, guidelines have variably endorsed both starting and avoiding antithrombotic drugs after ICH.

The investigators therefore want to study the effect and safety of using antithrombotic drugs after ICH. Furthermore, since findings on MRI can be biomarkers for subsequent bleeding, there will also be performed a sub-study of the association between such findings on MRI and risk of recurrent ICH during treatment with antithrombotic drugs.

Patients with ICH during the last 6 months and with an indication for antithrombotic drugs will be included. Patients with vascular disease and indication for antiplatelet drugs will be randomised to antiplatelet treatment vs. no antithrombotic treatment. Patients with atrial fibrillation and indication for anticoagulant treatment will be randomised to anticoagulant treatment vs. no anticoagulant treatment. The follow up period is 2 years, and the primary effect variable is new ICH. The investigators will also assess new intracranial haemorrhage, extracranial haemorrhage and ischemic events, and functional and cognitive outcome.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Torgeir Bruun Wyller, PhD; Phone Number: 004791166682; Email: t.b.wyller@medisin.uio.no

Study Locations

• Denmark
  • Copenhagen, Denmark, DK-2730
    • Recruiting
    • Herlev Gentofte Hospital
    • Contact: Christina Rostrup Kruuse, PhD; Email: christina.kruuse@regionh.dk
• Norway
  • Oslo, Norway, 0424
    • Recruiting
    • Oslo University Hospital
    • Contact: Kristin Larsen, MD; Phone Number: 004798671138; Email: k.t.larsen@medisin.uio.no
    • Contact: Ole Morten Rønning, PhD; Phone Number: 004745601774; Email: o.m.ronning@medisin.uio.no
• Sweden
  • Umeå, Sweden, SE-90185
    • Recruiting
    • Umeå University Hospital
    • Contact: Eva-Lotta Glader, PhD; Email: eva-lotta.glader@umu.se
    • Contact: Johanna Pennlert, PhD; Email: johanna.pennlert@umu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient age ≥18 years.

• Spontaneous, primary ICH, of ≥1 day, but not more than 180 days after onset of qualifying ICH, i.e.:

  • No preceding traumatic brain injury, based on history from the patient/witness of spontaneous symptom onset, and brain imaging appearances consistent of spontaneous ICH (i.e. any brain/bone/soft tissue appearances of trauma must have occurred secondary to a spontaneous ICH)
  • No 'secondary' or underlying structural cause (e.g. haemorrhagic transformation of an ischaemic stroke, aneurysm, tumour, arteriovenous malformation, or intracerebral venous thrombosis)
• Patient have indication for antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of ischaemic events, either antiplatelet drugs (for patients with vascular disease), or anticoagulant drug for patients with atrial fibrillation.
• Consent to randomisation from the patient (or personal / legal / professional representative if the patient does not have mental capacity).
• MRI (or CT) is performed before randomisation.

Exclusion Criteria:

• Clear indication for antiplatelet or anticoagulant treatment (e.g. prosthetic heart valves).
• Contraindications to the antithrombotic drug that will be administered.
• Patient is pregnant, breastfeeding, or of childbearing age and not taking contraception.
• For patients examined with MRI: Contraindication for brain MRI
• Malignancy with life expectancy less than 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Antithrombotic treatment; For patients with vascular disease and indication for antiplatelet drugs: Antiplatelet drugs; For patients with atrial fibrillation and indication for anticoagulant drugs: Anticoagulant drugs	Drug: Antithrombotic Agent; Anticoagulant or antiplatelet drugs
NO_INTERVENTION: No antithrombotic treatment; For patients with indication for antiplatelet drugs: No antithrombotic drugs For patients with atrial fibrillation and indication for anticoagulant drugs: No anticoagulant drugs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatal or non-fatal symptomatic ICH.	Neurological deterioration or death associated with intracerebral haemorrhage found on CT scan, MRI, or autopsy.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional outcome	Modified Rankin Scale score	2 years
Death of any cause	Death of any cause	2 years
Vascular death	Death of vascular cause	2 years
Symptomatic epidural, subdural, or subarachnoid haemorrhage	Neurological deterioration or death associated with epidural, subdural, or subarachnoid haemorrhage found on CT scan, MRI, or autopsy.	2 years
Symptomatic major extracranial haemorrhage	Clinically overt bleeding associated with one or more of: Transfusion of >2 red cell units of blood; A fall in haemoglobin of 2 g/dL, (1.24 mmol/L); Bleeding into retroperitoneum, intraocular space or major joint; Bleeding leading to permanent treatment cessation	2 years
Ischaemic events	Transient ischaemic attack, ischaemic stroke, unstable angina, acute myocardial infarction (type 1), peripheral arterial occlusion, mesenteric ischaemia, retinal arterial occlusion, deep vein thrombosis or pulmonary embolism.	2 years
Cognitive outcome at two years	Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)	2 years

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Torgeir Bruun Wyller, PhD, Oslo University Hospital

Publications and helpful links

General Publications

• Li L, Poon MTC, Samarasekera NE, Perry LA, Moullaali TJ, Rodrigues MA, Loan JJM, Stephen J, Lerpiniere C, Tuna MA, Gutnikov SA, Kuker W, Silver LE, Al-Shahi Salman R, Rothwell PM. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol. 2021 Jun;20(6):437-447. doi: 10.1016/S1474-4422(21)00075-2. Erratum In: Lancet Neurol. 2021 Jun 9;:
• 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): July 1, 2018
• Primary Completion (ANTICIPATED): June 1, 2023
• Study Completion (ANTICIPATED): June 1, 2031

Study Registration Dates

• First Submitted: June 8, 2017
• First Submitted That Met QC Criteria: June 13, 2017
• First Posted (ACTUAL): June 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Intracerebral hemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Hemorrhage; Intracranial Hemorrhages; Cerebral Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents
• Other Study ID Numbers: Version/date 180315

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared within the COCROACH Collaboration.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes