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Brief Summary:
The purpose of this study is to try to find the best dose of the new drug BAY 2433334 to give to participants and to look at how well BAY 2433334 works on top of antiplatelet therapy in patients following a recent non cardioembolic ischemic stroke which occurs when a blood clot that has not formed in the heart travelled to the brain. BAY 2433334, works by blocking a step of the blood clotting process in our body and thins the blood and is a so called oral FXIa inhibitor.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Non-cardioembolic Ischemic Stroke | Drug: BAY2433334 Other: BAY2433334 matching placebo | Phase 2 |
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| Study Type : | Interventional (Clinical Trial) |
| ActualEnrollment : | 1808 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Multicenter, Randomized, Placebo-controlled, Double-blind, Parallel Group, Dose-finding Phase 2 Study to Evaluate Efficacy and Safety of BAY2433334 in Patients Following an Acute Non-cardioembolic Ischemic Stroke |
| Actual Study Start Date : | June 15, 2020 |
| Actual Primary Completion Date : | February 18, 2022 |
| Actual Study Completion Date : | February 18, 2022 |
Resource links provided by the National Library of Medicine 
MedlinePlus related topics: BloodClots IschemicStroke
U.S. FDA Resources
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| Arm | Intervention/treatment |
|---|---|
| Experimental: BAY2433334 high dose | Drug: BAY2433334 Tablet, taken orally once a day. |
| Experimental: BAY2433334 medium dose | Drug: BAY2433334 Tablet, taken orally once a day. |
| Experimental: BAY2433334 low dose | Drug: BAY2433334 Tablet, taken orally once a day. |
| Placebo Comparator: BAY2433334 matching placebo | Other: BAY2433334 matching placebo Tablet, taken orally once a day. |
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Primary Outcome Measures :
- Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke or Covert Brain Infarcts Detected by Magnetic Resonance Imaging (MRI) [TimeFrame:From baseline up to 26 weeks]
Ischemic stroke was defined as either of : 1) Rapid onset (or present on awakening) of a new focal neurological deficit with clinical (>24 hours symptoms/signs) or imaging evidence of infarction that was not attributable to a non-ischemic cause; 2) Acute worsening of an existing focal neurological deficit that was judged to be attributable to a new infarction or extension of the previous infarction in the same vascular territory, based on persisting symptoms/signs or imaging evidence of infarction and no evidence of a non-ischemic etiology. If imaging was inconclusive, persistent symptoms/signs must be significant (worsening of NIHSS score of 4 or more) and sustained (duration of ≥24 hours or until death). Covert brain infarcts were defined as incident infarcts detected by serial MRI in the absence of an adjudicated stroke consistent with the location of the infarct. MRI criteria for brain infarction were available in the MRI procedures manual.
- Safety-Number of Participants With Composite of International Society on Thrombosis and Hemostasis (ISTH) Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding [TimeFrame:From baseline up to 52 weeks]
ISTH Major Bleeding criteria: 1. Fatal bleeding, and/or 2. Symptomatic bleeding in a critical area or organ (intracranial, intraocular, intraspinal, pericardial, retroperitoneal, intraarticular, or intramuscular with compartment syndrome), and/or 3. Clinically overt bleeding associated with a recent decrease in the hemoglobin level of ≥ 2 g/dL (20 g/L; 1.24 mmol/L) compared to the most recent hemoglobin value available before the event, and/or 4. Clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. ISTH Clinically Relevant Non-Major Bleeding is considered any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding, but does meet at least one of the following criteria 1. requiring medical intervention by a healthcare professional. 2. leading to hospitalization or increased level of care. 3. prompting a face to face (i.e. not just a telephone or electronic communication) evaluation.
Secondary Outcome Measures :
- Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke and Covert Brain Infarcts Detected by MRI, Cardiovascular (CV) Death, Myocardial Infarction (MI) and Systemic Embolism. [TimeFrame:From baseline up to 26 weeks]
CV death included death due to stroke, MI, heart failure or cardiogenic shock, sudden death or any other death due to other cardiovascular causes. Death due to non-traumatic hemorrhage was included. Acute MI was used when there was evidence of myocardial necrosis in a clinical setting consistent with acute myocardial ischemia. According to MI Universal Definition from 2018 the diagnosis of MI required the combination of: 1) Presence of acute myocardial injury, and 2) Evidence of acute myocardial ischemia derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging, or in case of post-mortem pathological findings irrespective of biomarker values. Systemic embolism was defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms (this did not include thromboembolism of the pulmonary vasculature or venous thrombosis).
- Efficacy-Number of Participants With Symptomatic Ischemic Stroke [TimeFrame:From baseline up to 52 weeks]
Definition of symptomatic ischemic stroke can be referred to first Primary endpoint.
- Efficacy-Number of Participants With Covert Brain Infarcts Detected by MRI [TimeFrame:From baseline up to 26 weeks]
Definition of covert brain infarcts can be referred to first Primary endpoint.
- Efficacy-Number of Participants With Symptomatic Ischemic Stroke, CV Death, MI [TimeFrame:From baseline up to 52 weeks]
Definition of symptomatic ischemic stroke can be referred to first Primary endpoint. Definition of CV death and MI can be referred to first Second endpoint.
- Efficacy-Number of Participants With Symptomatic Ischemic and Hemorrhagic Stroke [TimeFrame:From baseline up to 52 weeks]
Definition of symptomatic ischemic can be referred to fourth secondary endpoint. Hemorrhagic stroke was defined as an acute, atraumatic extravasation of blood into the brain parenchyma, intraventricular or subarachnoid space with associated neurological symptoms. This did not include microbleeds or hemorrhagic transformation of an ischemic stroke.
- Efficacy-Number of Participants With Disabling Stroke (mRS≥4) [TimeFrame:From baseline up to 52 weeks]
Modified ranking score (mRS): 0-No symptoms at all; 1-No significant disability despite symptoms; despite symptoms, able to carry out all usual duties and activities; 2-Slight disability; unable to carry out all previous activities but able to look after own affairs without assistance; 3-Moderate disability; requiring some help, but able to walk without assistance; 4-Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5-Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6-Death.
- Efficacy-Number of Participants With All-cause Mortality [TimeFrame:From baseline up to 52 weeks]
- Safety-Number of Participants With All Bleeding [TimeFrame:From baseline up to 52 weeks]
All bleeding events occurred from first intake of study intervention until 2 days after the last intake of study intervention.
- Safety-Number of Participants With ISTH Major Bleeding [TimeFrame:From baseline up to 52 weeks]
Definition of ISTH major bleeding can be referred to second Primary endpoint.
- Safety-Number of Participants With ISTH CRNM Bleeding [TimeFrame:From baseline up to 52 weeks]
Definition of ISTH CRNM bleeding can be referred to second Primary endpoint.
- Safety-Number of Participants With ISTH Minor Bleeding [TimeFrame:From baseline up to 52 weeks]
All other overt bleeding episodes not meeting the above criteria for ISTH major or CRNM bleeding were classified as minor bleeding (e.g. bleeding from a minor wound that does not prompt a face-to-face evaluation for a physical examination or laboratory testing).
- Safety-Number of Participants With Intracerebral Hemorrhage (Non-traumatic) [TimeFrame:From baseline up to 52 weeks]
Non-traumatic intracerebral hemorrhage was defined as a hemorrhagic stroke on the "recurrent stroke" CRF page that is in addition classified as a bleeding with bleeding site intracranial (-subarachnoid, -intraparenchymal [excluding microbleeds], or -intraventricular) and spontaneous causality of bleeding, excluding all symptomatic and hemorrhagic transformation (defined by the PT "hemorrhagic transformation").
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Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 45 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Participant must be 45 years of age and older at the time of signing the informed consent
-
Non-cardioembolic ischemic stroke with
- persistent signs and symptoms of stroke lasting for ≥ 24 hours OR
- acute brain infarction documented by computed tomography (CT) or MRI AND
- with the intention to be treated with antiplatelet therapy during the study conduct
- Imaging of brain (CT or MRI) ruling out hemorrhagic stroke or another pathology that could explain symptoms (e.g. brain tumor, abscess, vascular malformation)
-
Severity of index event nearest the time of randomization:
- Part A: minor stroke (defined as National Institutes of Health Stroke Scale (NIHSS) ≤ 7) can be enrolled
- Part B: participants with minor or moderate stroke and NIHSS ≤ 15 can be enrolled. Participants undergoing thrombolysis or endovascular therapy (mechanical thrombectomy) can be enrolled but at the earliest 24 hours after the intervention
- Randomization within 48 hours after the onset of symptoms of the index event (or after patients were last known to be without symptoms in case of wake-up stroke)
- Ability to conduct an MRI either before randomization or within 72 hours after randomization
Exclusion Criteria:
- Prior ischemic stroke within last 30 days of index event
- History of atrial fibrillation or suspicion of cardioembolic source of stroke
- Dysphagia with inability to safely swallow study medication
- Contraindication to perform brain MRI
- Part A only: thrombolysis or endovascular therapy (mechanical thrombectomy) performed for index event
- Active bleeding; known bleeding disorder, history of major bleeding (intracranial, retroperitoneal, intraocular) or clinically significant gastrointestinal bleeding within last 6 months of randomization.
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Top of Page Study Description Study Design
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Information from the National Library of Medicine
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): NCT04304508
Locations
Show 197 study locations
Sponsors and Collaborators
Bayer
Population Health Research Institute
Study Documents (Full-Text)
Documents provided by Bayer:
Study Protocol [PDF] October 24, 2019
Statistical Analysis Plan [PDF] January 26, 2022
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Additional Information:
Click here to find information about studies related to Bayer Healthcare products conducted in Europe. 
Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Shoamanesh A, Mundl H, Smith EE, Masjuan J, Milanov I, Hirano T, Agafina A, Campbell B, Caso V, Mas JL, Dong Q, Turcani P, Christensen H, Ferro JM, Veltkamp R, Mikulik R, De Marchis GM, Robinson T, Lemmens R, Stepien A, Greisenegger S, Roine R, Csiba L, Khatri P, Coutinho J, Lindgren AG, Demchuk AM, Colorado P, Kirsch B, Neumann C, Heenan L, Xu L, Connolly SJ, Hart RG; PACIFIC-Stroke Investigators. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. 2022 Sep 24;400(10357):997-1007. doi: 10.1016/S0140-6736(22)01588-4. Epub 2022 Sep 2.
| Responsible Party: | Bayer |
| ClinicalTrials.gov Identifier: | NCT04304508 |
| Other Study ID Numbers: | 19766 2019-003431-33 ( EudraCT Number ) |
| First Posted: | March 11, 2020 Key Record Dates |
| Results First Posted: | April 19, 2023 |
| Last Update Posted: | April 19, 2023 |
| Last Verified: | April 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Plan Description: | Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
| Stroke Ischemic Stroke Cerebral Infarction Ischemia Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases | Vascular Diseases Cardiovascular Diseases Pathologic Processes Brain Infarction Brain Ischemia Infarction Necrosis |
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