Registration of Idarucizumab for Patients With IntraCranial Hemorrhage

Study Overview
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Brief Summary
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This multicenter, prospective, observational, non-interventional study investigates patients with intracranial hemorrhage under effective anticoagulation with dabigatran or vitamin-K antagonist (VKA). Routine data will be collected during hospitalization. Patients aged 18 years or older under effective therapy with dabigatran and symptomatic intracranial bleeding confirmed by cerebral imaging and treated with idarucizumab will be compared to patients under effective treatment with VKA at the time of onset of the intracranial bleeding. Ninety-five dabigatran patients who provided written informed consent for data transmission will be included. As control group retrospective and anonymized data of 285 VKA patients patients under VKA treatment and admitted to RIC-ICH study centers will be used. For each patient receiving idarucizumab, three patients with intracranial hemorrhage under effective treatment with VKA, will be included (retrospective) in the study. In addition, data of VKA patients will be transferred from the RASUNOA-PRIME and the Erlanger Hirnblutungs-Register.

Official Title
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Registration of Idarucizumab for Patients With IntraCranial Hemorrhage (RIC-ICH)

Conditions
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Intracranial Hemorrhage

Intervention / Treatment
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* Drug: Dabigatran Etexilate Oral Capsule [Pradaxa]
* Drug: Idarucizumab 2.5 GM/50 ML Intravenous Solution [PRAXBIND]
* Drug: Vitamin K antagonist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (dabigatran-group): Age ≥18 years at enrollment Patients willing and able to provide written informed consent for data transmission (exceptions/special cases for patients who are not legally competent to sign informed consent for data transmission). Patients with primary intracranial hemorrhage as confirmed with CT. Patients under effective anticoagulation treatment with dabigatran at the time of admission (TT>60 sec. or last intake of medication <24hours). Patients treated with Idarucizumab (2x2.5 g recommended) may still be included the day after the administration of Praxbind, or on the following working day if treatment was carried out on the weekend. inclusion (signed informed consent) as soon as possible after start of symptoms of initial ICH event, but before discharge. Inclusion Criteria (control-group): - Patients with intracranial hemorrhage under effective anticoagulation treatment with VKA (INR ≥ 1,7) having been initially treated in the past in the study center. Exclusion Criteria (dabigatran-group): Additional therapy with PCC, aPCC or factor VII (in patients under dabigatran). Exclusion Criteria (all patients): - Start of symptoms of initial ICH event > 24 h before admission to hospital.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| dabigatran-group<br>Patients with the anticoagulating therapy dabigatran and onset of clinically symptomatic intracranial hemorrhage, that is treated with idarucizumab. | Drug: Dabigatran Etexilate Oral Capsule [Pradaxa]<br>* Dabigatran is the most frequently used direct thrombin inhibitor in secondary stroke prevention in patients with atrial fibrillation.<br>Drug: Idarucizumab 2.5 GM/50 ML Intravenous Solution [PRAXBIND]<br>* Idarucizumab is the current standard therapy in patients with intracranial bleeding under anticoagulation with dabigatran.<br>|
| VKA-group<br>Patients under effective treatment with VKA and with intracranial hemorrhage. | Drug: Vitamin K antagonist<br>* This drug group includes the active substances phenprocoumon and warfarin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-hospital mortality rate | Intra-hospital mortality rate | From study inclusion until hospital discharge or 30 days after index event, whichever came first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in National Institutes of Health Stroke Scale (NIHSS) | Change in National Institutes of Health Stroke Scale (NIHSS) of ≥4 pts compared to initial NIHSS or worsening of NIHSS level of consciousness ≥1 point or increase of the volume of the intracranial bleeding or new intraventricular bleeding or death. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. | At hospital admission, 24 hours after admission and 72 hours after admission. | 
| Intracranial bleeding | Change in size/volume of > 33% or ≥ 6.5 ml of the intracranial bleeding evaluated by first CT | Between 24 and 72 hours after initial CT. | 
| Stroke severity | Change in stroke severity by ≥4 points based on National Institutes of Health Stroke Scale (NIHSS). The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. | 72 hours after hospital admission | 
| Functional status | Functional status according to modified Rankin Scale (mRS). The scale runs from 0-6, running from perfect health without symptoms to death: 0 - No symptoms, 1 - No significant disability, 2 - Slight disability, 3 - Moderate disability, 4 - Moderately severe disability, 5 - Severe disability, 6 - Dead. | At hospital discharge or 30 days after index event, whichever came first. | 
| Mortality rate | Mortality rate | 7 and 30 days after index event. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intracranial/intracerebral bleeding, stroke, transient ischemic attack (TIA), myocardial infarction, anticoagulation, dabigatran, idarucizumab, vitamin-k antagonists