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

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

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".

Study Overview

• Status: Completed
• Conditions: Intracranial Hemorrhage
• Intervention / Treatment: Drug: Dabigatran Etexilate Oral Capsule [Pradaxa]; Drug: Idarucizumab 2.5 GM/50 ML Intravenous Solution [PRAXBIND]; Drug: Vitamin K antagonist

• Study Type: Observational
• Enrollment (Actual): 104

Contacts and Locations

Study Locations

• Germany
  • Bad Aibling, Germany, 83043
    • Klinikum Schön Klinik Bad Aibling SE & Co. KG
  • Bad Homburg, Germany, 61352
    • Hochtaunuskliniken GmbH
  • Bad Neustadt An Der Saale, Germany, 97616
    • Rhön Klinikum Campus Bad Neustadt
  • Berlin, Germany, 12351
    • Vivantes Klinikum Neukölln
  • Berlin, Germany, 13509
    • Vivantes Humboldt Klinikum
  • Berlin, Germany, 12157
    • Vivantes Klinikum Auguste Viktoria
  • Bielefeld, Germany, 33617
    • Evangelisches Klinikum Bethel gGmbH
  • Bochum, Germany, 44791
    • Katholisches Klinikum Bochum gGmbH, St. Josef Hospital
  • Bonn, Germany, 53127
    • Universitätsklinkum Bonn
  • Celle, Germany, 29223
    • Klinikum Allgemeines Krankenhaus Celle
  • Cottbus, Germany, 03048
    • Carl-Thiem-Klinikum Cottbus gGmbH
  • Damme, Germany, 49401
    • Krankenhaus St. Elisabeth gGmbH
  • Freiburg, Germany, 79106
    • Albert-Ludwigs-Universität Freiburg
  • Gera, Germany, 07548
    • SHR Wald-Klinikum Gera GmbH
  • Göttingen, Germany, 37075
    • Georg-August-Universität Göttingen, Universitätsmedizin
  • Halle, Germany, 06120
    • Klinikum Martha Maria
  • Hamburg, Germany, 22291
    • Asklepios Klinik Barmbek
  • Hamburg, Germany, 22043
    • Asklepios Klinik Wandsbek
  • Hamburg, Germany, 22307
    • Universitätsklinikum Hamburg-Eppendorf
  • Hausham, Germany, 83734
    • Klinikum Agatharied GmbH
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Hessisch Oldendorf, Germany, 31840
    • BDH-Klinik Hessisch Oldendorf
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • Leipzig, Germany, 04103
    • Universität Leipzig
  • Lohr, Germany, 97816
    • Klinikum Main-Spessart Lohr
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes-Guttenberg-Universität Mainz
  • Osnabrück, Germany, 49076
    • Klinikum Osnabruck
  • Recklinghausen, Germany, 45657
    • Klinikum Vest Knappschaftskrankenhaus
  • Sanderbusch, Germany, 26452
    • Klinikum Nordwest Krankenhaus Sande
  • Stuttgart, Germany, 70174
    • Klinikum der Landeshauptstadt Stuttgart gKAöR
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
  • Wismar, Germany, 23966
    • Sana HANSE-Klinikum Wismar GmbH

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with the anticoagulating therapy dabigatran admitted with a clinically symptomatic intracranial bleeding will be included in the study, if they have been treated with idarucizumab (dabigatran-group). It is assumed that some of these patients will have been given an antiplatelet drug as co-medication.

As reference population, patients with intracranial hemorrhage under effective treatment with VKA (INR ≥ 1,7) treated in the same center will be used (VKA-group). These patients usually have been treated with some antagonist to VKA (or no reversal therapy at all).

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University Hospital, Essen

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2019
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: August 8, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 20, 2019

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: stroke; myocardial infarction; anticoagulation; transient ischemic attack (TIA); dabigatran; idarucizumab; intracranial/intracerebral bleeding; vitamin-k antagonists
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hemorrhage; Intracranial Hemorrhages; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrin Modulating Agents; Protease Inhibitors; Micronutrients; Vitamins; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K; Dabigatran
• Other Study ID Numbers: RIC-ICH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No