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Atrial Fibrillation (AF)Phase 2PACIFIC-AFNCT04218266

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.

A Phase 2 study testing BAY2433334 and Apixaban in people with Atrial Fibrillation (AF), run by Bayer at 93 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 in patients with irregular heartbeat (atrial fibrillation) that can lead to blood clots, stroke and other heart-related complications. Read more about this study

Who is it for?
Ages 45 years and older
Conditions the study is for
Atrial Fibrillation (AF)
What is being tested?
BAY2433334 and Apixaban
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
755 participants
Where
93 sitesin 14 countries
Study dates
30 Jan 2020to 8 Oct 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participant must be 45 years of age or older at the time of signing the informed consent.
  • Participant with AF documented by ECG evidence with
  • CHA2DS2-VASc score ≥ 2 if male or CHA2DS2-VASc score ≥ 3 if female
  • 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

Who cannot join

  • 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

Trial locations and contacts

93 sites in 14 countries.

93 sites in 14 countries

Japan9 sites

  • Nishiarai Heart Central Clinic

    Adachi-ku, Tokyo, 123-0845

  • Minamino Cardiovascular Hospital

    Hachiōji, Tokyo, 192-0918

  • Tokyo Angel Hospital

    Hachiōji, Tokyo, 193-0811

  • Hyogo Prefectural Harima-Himeji General Medical Center

    Himeji, Hyōgo, 670-8560

  • Nakamura Cardiovascular Clinic

    Itoshima, Fukuoka, 819-1104

  • Kishiwada Tokushukai Hospital

    Kishiwada, Osaka, 596-0042

  • Koto Hospital

    Koto-ku, Tokyo, 136-0072

  • Hayama Heart Center

    Miura-gun, Kanagawa, 240-0116

  • Yao Tokushukai General Hospital

    Yao, Osaka, 581-0011

Other trials in Japan

Austria8 sites

  • Krankenhaus St. Josef Braunau

    Braunau am Inn, Upper Austria, 5280

  • Landeskrankenhaus Feldkirch

    Feldkirch, Vorarlberg, 6807

  • Medizinische Universität Graz

    Graz, Styria, 8036

  • Medizinische Universität Innsbruck

    Innsbruck, Tyrol, 6020

  • Ordensklinikum Linz GmbH Elisabethinen

    Linz, Upper Austria, 4020

  • Uniklinikum Salzburg - Landeskrankenhaus

    Salzburg, 5020

  • Universitätsklinikum AKH Wien

    Vienna, 1090

  • Klinik Floridsdorf - Krankenhaus Nord

    Vienna, 1210

Other trials in Austria

Hungary8 sites

  • Tagore Medical Center

    Balatonfüred, 8230

  • University of Semmelweis/ Semmelweis Egyetem

    Budapest, 1122

  • Magyar Honvedseg Egeszsegugyi Kozpont

    Budapest

  • Kanizsai Dorottya Hospital

    Nagykanizsa, 8800

  • Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.

    Nyíregyháza, 4400

  • Pecsi Tudomanyegyetem Klinikai Kozpont

    Pécs, 7624

  • Tolna Megyei Balassa Janos Korhaz

    Szekszárd, 7100

  • Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz

    Szentes, 6600

Other trials in Hungary

Netherlands8 sites

  • Academisch Medisch Centrum (AMC)

    Amsterdam, 1105 AZ

  • Ziekenhuis Rijnstate

    Arnhem, 6815 AD

  • Amphia Ziekenhuis, locatie Molengracht

    Breda, 4818 CK

  • Albert Schweitzer Ziekenhuis, Dordwijk

    Dordrecht, 3318 AT

  • Medisch Spectrum Twente

    Enschede, 7511 JX

  • Martini Ziekenhuis, Locatie van Swieten

    Groningen, 9728 NT

  • Spaarne Gasthuis - locatie Zuid

    Haarlem, 2035 RC

  • Maastricht UMC

    Maastricht, 6229 HX

Other trials in Netherlands

Belgium7 sites

  • Imeldaziekenhuis - St-Elisabethkliniek

    Bonheiden, 2820

  • AZ St-Jan Brugge Oostende AV

    Bruges, 8000

  • UZ Antwerpen

    Edegem, 2650

  • Jessa Ziekenhuis

    Hasselt, 3500

  • UZ Leuven Gasthuisberg

    Leuven, Vlaams Brabant, 3000

  • VZW Emmaus

    Mechelen, 2800

  • AZ Delta

    Roeselare, 8800

Other trials in Belgium

France7 sites

  • Hôpital Henri Mondor

    Créteil, 94010

  • Centre Hospitalier Départemental Vendée

    La Roche-sur-Yon, 85025

  • Centre Hospitalier Louis Pasteur

    Le Coudray, 28630

  • Hopital Bichat - Paris

    Paris, 75018

  • Centre Hospitalier Régional - Saint Brieuc

    Saint-Brieuc, 22000

  • Hôpital de Rangueil - Toulouse

    Toulouse, 31403

  • Centre Hospitalier - Valenciennes Cedex

    Valenciennes, 59322

Other trials in France

Italy7 sites

  • AUSL Toscana Sud-Est

    Arezzo, Tuscany, 52044

  • AUSL Toscana Sud-Est

    Arezzo, Tuscany, 52100

  • ASUR Marche - Area Vasta 5

    Ascoli Piceno, The Marches, 63074

  • ASST Spedali Civili di Brescia

    Brescia, Lombardy, 25123

  • IRCCS Ospedale Policlinico San Martino

    Genoa, Liguria, 16132

  • A.O. di Perugia

    Perugia, Umbria, 06129

  • A.O.U. Policlinico Umberto I

    Rome, Lazio, 00161

Other trials in Italy

Sweden7 sites

  • Falu Lasarett

    Falun, 791 82

  • Clemenstorget Hjärtmottagning

    Lund, 222 21

  • Avdelningen för kliniska prövningar AKP

    Örebro, 703 62

  • Östersunds Sjukhus

    Östersund, 831 83

  • Skellefteå Lasarett

    Skellefteå, 931 86

  • Södersjukhuset AB

    Stockholm, 118 83

  • Danderyds sjukhus

    Stockholm, 182 88

Other trials in Sweden

Czechia6 sites

  • Fakultni nemocnice Plzen - Lochotin

    Pilsen, 304 60

  • Fakultni nemocnice Kralovske Vinohrady

    Prague, 100 34

  • Institut Klinicke a Experimentalni Mediciny

    Prague, 140 21

  • Fakultni nemocnice v Motole

    Prague, 150 06

  • Nemocnice Slany

    Slaný, 274 01

  • Krajska nemocnice T. Bati, a.s.

    Zlín, 762 75

Other trials in Czechia

Latvia6 sites

  • Doctor's Practice in Cardiology

    Daugavpils, LV-5401

  • Daugavpils Regional Hospital

    Daugavpils, LV-5417

  • Liepaja Regional Hospital

    Liepāja, LV-3414

  • 1st Riga Clinical Hospital

    Riga, LV-1001

  • P. Stradins Clinical University Hospital

    Riga, LV-1002

  • Riga East Clinical University Hospital "Gailezers"

    Riga, LV-1038

Other trials in Latvia

Switzerland6 sites

  • Kantonsspital Aarau

    Aarau, Canton of Aargau, 5001

  • Universitätsspital Basel

    Basel, Canton of Basel-City, 4031

  • Inselspital Universitätsspital Bern

    Bern, 3010

  • Hôpital Cantonal Universitaire de Genève

    Geneva, 1211

  • Ospedale regionale di Lugano

    Lugano, 6900

  • Kantonsspital St. Gallen

    Sankt Gallen, Canton of St. Gallen, 9007

Other trials in Switzerland

Spain5 sites

  • Ciutat Sanitària i Universitaria de la Vall d'Hebron

    Barcelona, 08035

  • Hospital de la Santa Creu i de Sant Pau | Cardiología

    Barcelona, 08041

  • Ciutat Sanitària i Universitària de Bellvitge

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Virgen de la Victoria

    Málaga, 29010

Other trials in Spain

United Kingdom5 sites

  • St Richard's Hospital

    Chichester, West Sussex, PO19 6SE

  • Staploe Medical Centre

    Ely, Cambridgeshire, CB7 5SQ

  • Northwick Park Hospital

    Harrow, London, HA1 3UJ

  • Heart and Chest Hospital

    Liverpool, L14 3PE

  • Queen Elizabeth II Hospital

    Welwyn Garden City, Hertfordshire, AL7 4HQ

Other trials in United Kingdom

Canada4 sites

  • Queen Elizabeth II Health Sciences Centre

    Halifax, Nova Scotia, B3H 3A7

  • Montreal Heart Institute

    Montreal, Quebec, H1T 1C8

  • Clinique Sante Cardio MC

    Montreal, Quebec, H1T 3Y7

  • Institut universitaire de cardiologie et de pneumologie

    Ste-Foy, Quebec, G1V 4G5

Other trials in Canada

About this study

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

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.

Being tested
BAY2433334, Apixaban, BAY2433334 matching placebo, Apixaban matching placebo
Medical subject headings
Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BAY2433334Drug

    Tablet, taken orally once a day.

  • ApixabanDrug

    Capsule, taken orally twice a day.

  • BAY2433334 matching placeboOther

    Tablet, taken orally once a day.

  • Apixaban matching placeboOther

    Capsule, taken orally twice a day.

Study groups in NCT04218266
Study groupRoleWhat they receive
BAY2433334 50mg+Apixaban matching placeboExperimentalNot described
Receives: Drug: BAY2433334; Other: Apixaban matching placebo
BAY2433334 20mg+Apixaban matching placeboExperimentalNot described
Receives: Drug: BAY2433334; Other: Apixaban matching placebo
BAY2433334 matching placebo+ApixabanActive comparatorApixaban 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.
Receives: Drug: Apixaban; Other: BAY2433334 matching placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Composite of International Society on Thrombosis and Hemostasis (ISTH) Major Bleeding or Clinically Relevant Non-major (CRNM) Bleeding

    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.

    Measured: 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)

Secondary outcomes (4)

  1. Number of Participants With All Bleeding

    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).

    Measured: 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)

  2. Number of Participants With ISTH Major Bleeding

    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.

    Measured: 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)

  3. Number of Participants of ISTH Clinically Relevant Non-major (CRNM) Bleeding

    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.

    Measured: 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)

  4. Number of Participants With ISTH Minor Bleeding

    All other overt bleeding episodes not meeting ISTH Major Bleeding criteria or clinically relevant non major bleeding were classified as minor bleeding.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2020
  2. Study start30 Jan 2020
  3. Primary completion8 Oct 2021
  4. Study completion8 Oct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
755 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04218266
Sponsor's protocol ID
19765
Other IDs
2019-002365-35, 2019
Acronym
PACIFIC-AF
Status last verified
Oct 2022
First submitted
2 Jan 2020
Last updated
27 Oct 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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.

Publications

  • Privitera S, Sedghamiz H, Hartenstein A, Vaitsiakhovich T, Kleinjung F. An evolutionary algorithm for the direct optimization of covariate balance between nonrandomized populations. Pharm Stat. 2024 May-Jun;23(3):288-307. doi: 10.1002/pst.2352. Epub 2023 Dec 18.

    PubMed 38111126

  • Piccini JP, Caso V, Connolly SJ, Fox KAA, Oldgren J, Jones WS, Gorog DA, Durdil V, Viethen T, Neumann C, Mundl H, Patel MR; PACIFIC-AF Investigators. Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study. Lancet. 2022 Apr 9;399(10333):1383-1390. doi: 10.1016/S0140-6736(22)00456-1. Epub 2022 Apr 3.

    PubMed 35385695

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BAY2433334 and Apixaban in people with Atrial Fibrillation (AF), run by Bayer at 93 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 93 sites in Japan, Austria, Hungary, Netherlands, Belgium and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04218266, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2022.

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