Study to Gather Information About the Proper Dosing of the Oral FXIa Inhibitor BAY 2433334 and to Compare the Safety of the Study Drug to Apixaban, a Non-vitamin K Oral Anticoagulant (NOAC) in Patients With Irregular Heartbeat (Atrial Fibrillation) That Can Lead to Heart-related Complications. (PACIFIC-AF)
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| ClinicalTrials.gov Identifier: NCT04218266 |
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Recruitment Status :
Completed
First Posted : January 6, 2020
Results First Posted : October 27, 2022
Last Update Posted : October 27, 2022
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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 in patients with irregular heartbeat (atrial fibrillation) that can lead to blood clots, stroke and other heart-related complications. In addition researchers want to compare the safety of the study drug to apixaban, a non-vitamin K oral anticoagulant (NOAC) in patients with atrial fibrillation. This study is also done to learn how the drug in this study moves into, through and out of the body. 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.
Apixaban, works by reducing the production of blood clotting factors in our body and thins the blood and is a so called non-vitamin K oral anticoagulant (NOAC). Thinning the blood can prevent you from blood clots which can cause a stroke.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Atrial Fibrillation (AF) | Drug: BAY2433334 Drug: Apixaban Other: BAY2433334 matching placebo Other: Apixaban matching placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 755 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Multicenter, Randomized, Active Comparator-controlled, Double-blind, Double-dummy, Parallel Group, Dose-finding Phase 2 Study to Compare the Safety of the Oral FXIa Inhibitor BAY2433334 to Apixaban in Patients With Atrial Fibrillation |
| Actual Study Start Date : | January 30, 2020 |
| Actual Primary Completion Date : | October 8, 2021 |
| Actual Study Completion Date : | October 8, 2021 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: BAY2433334 50mg+Apixaban matching placebo |
Drug: BAY2433334
Tablet, taken orally once a day. Other: Apixaban matching placebo Capsule, taken orally twice a day. |
| Experimental: BAY2433334 20mg+Apixaban matching placebo |
Drug: BAY2433334
Tablet, taken orally once a day. Other: Apixaban matching placebo Capsule, taken orally twice a day. |
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Active Comparator: BAY2433334 matching placebo+Apixaban
Apixaban usual dose is 5 mg, reduced to 2.5 mg for participants with any 2 of the following criteria: age 80 years or older, body weight less than 60 kg, or serum creatinine level of 1.5 mg per dL or more.
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Drug: Apixaban
Capsule, taken orally twice a day. Other: BAY2433334 matching placebo Tablet, taken orally once a day. |
- Number of Participants With Composite of International Society on Thrombosis and Hemostasis (ISTH) Major Bleeding or Clinically Relevant Non-major (CRNM) Bleeding [ Time Frame: After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration) ]
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.
- Number of Participants With All Bleeding [ Time Frame: After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration) ]Adjudication of all bleeding events was performed by members of the Clinical events committee (CEC) who reviewed events in a blinded fashion and adjudicated and classified the following events in a consistent and unbiased manner according to the following classifications: ISTH (major, clinically relevant non-major and minor); Thrombolysis in myocardial infarction (TIMI major, minor, requiring medical attention, minimal); Bleeding Academic Research Consortium (BARC type 1, 2, 3, 5).
- Number of Participants With ISTH Major Bleeding [ Time Frame: After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration) ]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.
- Number of Participants of ISTH Clinically Relevant Non-major (CRNM) Bleeding [ Time Frame: After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration) ]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.
- Number of Participants With ISTH Minor Bleeding [ Time Frame: After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration) ]All other overt bleeding episodes not meeting ISTH Major Bleeding criteria or clinically relevant non major bleeding were classified as minor bleeding.
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| Ages Eligible for Study: | 45 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Participant must be 45 years of age or older at the time of signing the informed consent.
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Participant with AF documented by ECG evidence with
- CHA2DS2-VASc score ≥ 2 if male or CHA2DS2-VASc score ≥ 3 if female
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Indication for treatment with an oral anticoagulant in
- any participant currently not treated with an oral anticoagulant (e.g. treatment naïve) or alternatively,
- participant on a NOAC in case of at least one bleeding risk feature (history of a prior bleed within the last 12 months requiring medical attention and / or moderate renal dysfunction with eGFR 30-50 ml/min and / or current clinically indicated antiplatelet therapy with Acetylsalicylic acid(ASA) ≤ 100 mg)
- Written informed consent
Exclusion Criteria:
- Mechanical heart valve prosthesis
- Any degree of rheumatic mitral stenosis or moderate-to-severe, non-rheumatic mitral stenosis
- Atrial fibrillation due to a reversible cause, participants in sinus rhythm after successful ablation, or plan for cardioversion or ablation during study conduct
- Requirement for chronic anticoagulation (for a different indication than AF) or antiplatelet therapy (up to 100 mg ASA is allowed). Anticipated need for chronic therapy with Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Treated with a Vitamin K antagonist in the 30 days prior to screening
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): NCT04218266
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bayer |
| ClinicalTrials.gov Identifier: | NCT04218266 |
| Other Study ID Numbers: |
19765 2019-002365-35 ( EudraCT Number ) |
| First Posted: | January 6, 2020 Key Record Dates |
| Results First Posted: | October 27, 2022 |
| Last Update Posted: | October 27, 2022 |
| Last Verified: | October 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Availability of this study's data will later 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 |
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Atrial Fibrillation Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Apixaban Factor Xa Inhibitors |
Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anticoagulants |