Lead Investigator: Timo Uphaus, University Medical Center Mainz
Title of Proposal Research: Identifying patients with unknown stroke etiology who may benefit from a blood thining medication with Dabigatran by a clinically based scoring system
Vivli Data Request: 6498
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Stroke is affecting around 150 per 100.000 people world-wide and is a leading cause of physical disability. Around 80% of strokes can be attributed to the population above the age of 60 Years. Due to the demographic change and ageing of the population the number of stroke patients will increase world-wide. After a stroke, further diagnostics such as ultrasound, electrocardiogram and laboratory tests are mandatory in order to elucidate patients’ individual stroke cause. In around 20% of stroke patients, no individual stroke cause can be unraveled. Nonetheless, especially the patients with unknown stroke cause are at high risk to suffer from a second stroke. This might be explained by the fact, that the regularly prescribed blood thinning medication with aspirin is not strong enough to prevent blood blot formation within these patients. Therefore, recent studies tested whether a stronger blood thinning medication with Dabigatran (oral anticoagulation) is more effective in preventing a second stroke in patients with unknown stroke cause. The RESPECT-ESUS trial represents an example of such a study. However, stronger blood thinning medication with Dabigatran was found to be not superior to weaker blood thinning medication with aspirin in preventing a second stroke in patients with unknown stroke cause. Nonetheless, a subgroup of patients with structural abnormalities of the heart such as enlarged heart cavities and a higher risk of blood clot formation within these enlarged cavities might benefit from a stronger blood thinning medication with Dabigatran. We aim to identify these patients by applying a clinical risk score within the RESPECT-ESUS study cohort. This solely clinically based scoring system is taking patients’ individual stroke severity and patients’ age into account and is thereby able to identify patients with a high risk of blood clot formation with the heart. These patients with a higher risk of blood clot formation within the heart might have a potential benefit of stronger blood thinning medication with Dabigatran and might prevent a second stroke in this patient collective.
Statistical Analysis Plan:
All analyses are performed in the intention-to-treat population and the per-protocol-population. Analysis of data from patients lost to follow-up will be based on the last day their status was known. Missing values will be excluded. A Cox proportional hazard regression model for the subgroups defined by the AS5F score will be performed and adjusted for covariates unbalanced at the univariate level.
The following methods will be performed to control for bias (matching, covariate adjustment).
The ASF5-score will be calculated based on age at stroke onset, National Institute of Health Stroke Scale (NIHSS) <= 5 and, NIHSS > 5, and stroke vs. transient symptoms (transient ischemic attack, TIA) by taking advantage of the following formula: probability of paroxysmal atrial fibrillation detection within 72 hours = [exp(-9.21+0.07 x (age in years) + 0.87 x 1 (stroke and NIH-SS < 5) + 1.98 x 1 (stroke and NIHSS > 5] / [-9.21 x 0.07 + (age in years) x 0.87 * 1 (stroke and NIH-SS <= 5) + 1.98 x 1 (stroke and NIHSS > 5)].
Requested Studies:
Randomized, Double-blind, Evaluation in Secondary Stroke Prevention Comparing the EfficaCy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate (110 mg or 150 mg, Oral b.i.d.) Versus Acetylsalicylic Acid (100 mg Oral q.d.) in Patients With Embolic Stroke of Undetermined Source (RESPECT ESUS)
Sponsor: Boehringer Ingelheim
Study ID: NCT02239120
Sponsor ID: 1160.189
Summary of Results:
Due to distribution of Age and NIHSS within the study, and only patients with ischemic stroke being included within the study, the application of AS5F-score for risk stratification of participants wasn’t reasonable. So, we weren’t able to perform the previously planned analysis.