PREvention of STroke in Intracerebral haemorrhaGE Survivors With Atrial Fibrillation (PRESTIGE-AF)
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| ClinicalTrials.gov Identifier: NCT03996772 |
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Recruitment Status :
Recruiting
First Posted : June 25, 2019
Last Update Posted : February 18, 2021
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Atrial fibrillation (AF) is the most common form of irregular heart rhythm. In people with AF, blood clots often form in the heart, which can travel to the brain. Blockage of brain arteries by these clots is a major cause of stroke. This type of stroke is called an ischaemic stroke and approximately 15% of all ischaemic strokes are caused by AF.
People with AF are often prescribed a medication called an anticoagulant, which makes it less likely for blood clots to form and thus can prevent ischaemic strokes. However, anticoagulants also increase the risk of bleeding, so they are not suitable for everyone.
Some people who have AF have had a different type of stroke which is caused by bleeding in the brain, an intracerebral haemorrhage (ICH). These people are at increased risk of suffering both an ischaemic stroke (due to AF) and another ICH. It is not known whether it is best for these people to take an anticoagulant medication or not, as previous research studies did not include this group of people.
PREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillation (PRESTIGE-AF) is a research study on the best stroke prevention in people with atrial fibrillation (AF) who have recently had a bleeding in their brain, (ICH). This is a trial where half of the participants will take an anticoagulant medication, preventing blood clot formation, and half will not receive an anticoagulant. The direct oral anticoagulants (DOACs) that will be used in this trial are all licenced for use in the United Kingdom and within the European Union (EU) to prevent strokes in people with AF. However, the current licence does not extend to use with people who have had an ICH because it has not been tested in this group with a randomised controlled trial. DOACs will be tested in ICH survivors with AF because previous research trials have shown that people are up to 50% less likely to have bleeding complications in the brain with DOACs than with Warfarin (another commonly used anticoagulant).
The aim of PRESTIGE-AF is to answer the question of whether people with ICH and AF should take an anticoagulant medication or if it is better for them to avoid it.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Atrial Fibrillation Intracerebral Hemorrhage | Drug: Apixaban Oral Tablet Drug: Dabigatran Drug: Edoxaban Tablets Drug: Rivaroxaban | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 654 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | PREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillation is a phase 3b investigator-led, multicentre, parallel group, prospective randomised, open, blinded end-point assessment (PROBE) clinical trial comparing direct oral anticoagulants against no anticoagulation in patients with a recent intracerebral haemorrhage (ICH) and comorbid atrial fibrillation (AF). Randomisation will occur in a 1:1 ratio. Participants will be stratified according to two factors: lobar and non-lobar location of ICH and gender. Choice and dose of direct oral anticoagulant treatment and use of concomitant medication during the study treatment will be at the Principal Investigator´s discretion within the licensed doses for stroke prevention in AF patients in Europe. The control group will receive no anticoagulant but the use of an antiplatelet is at the Principal Investigator´s discretion who will use their clinical judgment to initiate an antiplatelet drug of their choice. |
| Masking: | Single (Outcomes Assessor) |
| Masking Description: | An Event Adjudication Committee (EAC) will be established. The EAC will consist of experts in relevant fields of the Study such as neurology, cardiology, and haematology. An event adjudication charter with clear definitions of pre-specified outcome events will be developed by the steering committee and agreed by the EAC. After formal training, the EAC will be provided with pseudonymised data for adjudication of pre-specified outcome events and serious adverse events using an online platform provided by the data management centre, Clinical Trials Center Wuerzburg at the University of Wuerzburg. |
| Primary Purpose: | Prevention |
| Official Title: | PREvention of STroke in Intracerebral haemorrhaGE Survivors With Atrial Fibrillation (PRESTIGE-AF) |
| Actual Study Start Date : | June 3, 2019 |
| Estimated Primary Completion Date : | May 31, 2022 |
| Estimated Study Completion Date : | November 30, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Direct Oral Anticoagulant
If the patient is randomized in this arm, a direct oral anticoagulant (DOAC) included:
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Drug: Apixaban Oral Tablet
Factor Xa Inhibitor
Other Name: Eliquis Drug: Dabigatran Direct Thrombin Inhibitor
Other Name: Pradaxa Drug: Edoxaban Tablets Factor Xa Inhibitor
Other Names:
Drug: Rivaroxaban Factor Xa Inhibitor
Other Name: Xarelto |
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No Intervention: No Anticoagulant
If the patient is randomized in this arm investigators will use their best judgment to decide upon the prescription of an antiplatelet drug of their choice or no such therapy
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- Time to the first incident ischemic stroke event. [ Time Frame: 3 years ]Statistics: product-limit estimations of the time to event ("survival") functions in both study groups. Measure of association: hazard ratio under the proportional hazard assumption.
- Time to the first recurrent intracerebral haemorrhage event. [ Time Frame: 3 years ]Statistics: product-limit estimations of the time to event ("survival") functions in both study groups. Measure of association: hazard ratio under the proportional hazard assumption.
- Rate of all stroke events [ Time Frame: 3 years ]Rate of all stroke events from the index date as number of events per 100 person years under observation in the study
- Rate of systemic embolism [ Time Frame: 3 years ]Rate of systemic embolism from the index date as number of events per 100 person years under observation in the study
- Rate of major adverse cardiac events [ Time Frame: 3 years ]Rate of major adverse cardiac events from the index date as number of events per 100 person years under observation in the study
- Rate of all-cause mortality [ Time Frame: 3 years ]Rate of all-cause mortality from the index date as number of events per 100 person years under observation in the study
- Rate of cardiovascular mortality [ Time Frame: 3 years ]Rate of cardiovascular mortality from the index date as number of events per 100 person years under observation in the study
- Rate of major haemorrhage [ Time Frame: 3 years ]Rate of major haemorrhage from the index date as number of events per 100 person years under observation in the study
- Rate of any intracranial haemorrhage [ Time Frame: 3 years ]Rate of any intracranial haemorrhage from the index date as number of events per 100 person years under observation in the study
- Rates of events (all strokes, systemic embolic event, myocardial infarction, cardiovascular mortality and major bleeding) [ Time Frame: 3 years ]Rates of events (all strokes, systemic embolic event, myocardial infarction, cardiovascular mortality and major bleeding) from the index date as number of events per 100 person years under observation in the study
- Rate of myocardial infarction [ Time Frame: 3 years ]Rate of myocardial infarction from the index date as number of events per 100 person years under observation in the study
- Rate of major bleedings [ Time Frame: 3 years ]Rate of major bleedings from the index date as number of events per 100 person years under observation in the study
- Quality of life: EQ-5D [ Time Frame: enrolment visit, 12 months, 24 months, 36 months ]
Quality of life: EQ-5D with 3 levels of severity for each of the 5 dimensions:
EQ-5D-3L
Statistics at 12, 24 (if required) and 36 months (if required) in both study groups:
Measures of central tendency and dispersion (mean and SD resp. median and interquartile range) for EQ VAS score (range 0 -100, higher values considered to be a better outcome) and for the EQ-5D-3L index score (range 0 - 1, higher values considered to be a better outcome) health profile: numbers and proportions reporting frequencies of the three levels within the EQ-5D dimensions in both study groups
- Cognitive function: the Montreal Cognitive Assessment (MoCA) [ Time Frame: enrolment visit, 12 months, 24 months, 36 months ]
Cognitive function: the Montreal Cognitive Assessment (MoCA) Total MoCA score: Range: 0 - 30, higher values considered to be a better outcome.
Statistics at 12, 24 (if required) and 36 months (if required) in both study groups:
Measures of central tendency and dispersion (mean and SD resp. median and inter quartile range). Frequencies for the values of the subscores in both study groups
- Psychological morbidity: the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: enrolment visit, 12 months, 24 months, 36 months ]
Psychological morbidity: the Hospital Anxiety and Depression Scale (HADS) Statistics at 12, 24 (if required) and 36 months (if required) in both study groups.
HADS anxiety and HADS depression score. For both scales range 0 - 21, smaller values considered to be a better outcome.
Median score and interquartile range for both scales in both study groups. Numbers and percentages of those patients classified as "non-cases", having mild disease, having moderate disease and having severe disease for both scales in both study groups according to the cut-off scores for HADS quantification.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age ≥ 18 years
- Written informed consent
- Recent history of a non-traumatic spontaneous intracerebral haemorrhage during the 6 months before enrolment
- Documented evidence of Atrial Fibrillation (paroxysmal, persistent or permanent)
- CHA2DS2-VASc score≥2 for male, and CHA2DS2-VASc score≥ 3 for female patients
- Availability of brain imaging following the index intracerebral haemorrhage
Exclusion Criteria:
- Patient lacks capacity to consent
- Fully dependent (Modified Rankin Scale Score >4)
- Women who are pregnant, breastfeeding, or plan to become pregnant during the Study period
- Women of childbearing potential who are unable or unwilling to take measures for effective contraception
- Intracerebral haemorrhage occurring within the last 14 days before enrolment
- Intracerebral haemorrhage occurring longer than 6 months before enrolment
- Intracerebral haemorrhage resulting from trauma or vascular malformation
- Another indication for long-term anticoagulation
- Patient has hypertension, which in the opinion of the investigator, is uncontrollable with medication
- Any contraindication (except intracerebral haemorrhage) to treatment with apixaban, dabigatran, edoxaban, rivaroxaban as per summary of product characteristics (SmPC).
- Absolute need for antiplatelet therapy at enrolment
- Presence of a left atrial appendage occlusion device (LAAO) or plan to implant an LAAO
- Presence of any medical, psychological, or psychiatric condition which in the opinion of the Principal or Co-Investigator would cause participation in the Study to be unwise
- Participation in any clinical study with an Investigational Medicinal Product within the past 30 days (observational studies are permitted)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03996772
| Contact: Kirsten H Harvey, MRes | +44(0)74 1414 1466 | kirsten.harvey@imperial.ac.uk | |
| Contact: Reena Patel | +44(0)20 3311 7296 | reena.patel12@imperial.ac.uk |
Show 28 study locations
| Principal Investigator: | Roland E Veltkamp, FESO | Imperial College London |
| Responsible Party: | Imperial College London |
| ClinicalTrials.gov Identifier: | NCT03996772 |
| Other Study ID Numbers: |
17HH4268 2018-002176-41 ( EudraCT Number ) 754517 ( Other Grant/Funding Number: European Union Horizon 2020 ) 236886 ( Other Identifier: IRAS ) |
| First Posted: | June 25, 2019 Key Record Dates |
| Last Update Posted: | February 18, 2021 |
| Last Verified: | February 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | IPD will be available to PRESTIGE-AF collaborators who are listed in the collaborators section. This is necessary to undertake the work as stipulated in the Grant Agreement with the European Union for this Project. |
| Supporting Materials: |
Study Protocol Clinical Study Report (CSR) |
| Time Frame: | The data will be available to PRESTIGE-AF collaborators from end of data collection and will be available throughout the archive period (15 years) through the archive system. |
| Access Criteria: | According to Study Protocol |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Atrial fibrillation Arrhythmias Cardiac Cerebral Hemorrhage Brain haemorrhage Intracerebral hemorrhage Cerebral haemorrhage Basal ganglia haemorrhage Putaminal haemorrhage Anticoagulants Oral anticoagulant Direct oral anticoagulant |
New oral anticoagulant Factor Xa inhibitors Direct thrombin inhibitor Dabigatran Apixaban Rivaroxaban Edoxaban DOAC NOAC Intracerebral haemorrhage Brain hemorrhage |
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Cerebral Hemorrhage Atrial Fibrillation Hemorrhage Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Intracranial Hemorrhages Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Vascular Diseases Rivaroxaban Apixaban Edoxaban Dabigatran Factor Xa Inhibitors Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anticoagulants |