PACIFIC-AF: 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.

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04218266
• Collaborator: (none)
• Enrollment: 753
• Locations: 93
• Arms: 3
• Actual Duration (Months): 20.3
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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 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 Design

• Study Type: Interventional
• Actual Enrollment: 753 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: Jan 30, 2020
• Actual Primary Completion Date: Oct 8, 2021
• Actual Study Completion Date: Oct 8, 2021

Arms and Interventions

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.
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.	Drug: Apixaban; Capsule, taken orally twice a day.; Other: BAY2433334 matching placebo; Tablet, taken orally once a day.

Outcome Measures

Primary Outcome Measures

1. Number of participants with composite of ISTH major and clinically relevant non-major bleeding [From baseline to end of treatment (12 weeks)]

   ISTH: International Society on Thrombosis and Hemostasis

Secondary Outcome Measures

1. Number of participants with all bleeding [From baseline to end of treatment (12 weeks)]

2. Number of participants with ISTH major bleeding [From baseline to end of treatment (12 weeks)]

3. Number of participants with ISTH clinically relevant non-major bleeding [From baseline to end of treatment (12 weeks)]

4. Number of participants with ISTH minor bleeding [From baseline to end of treatment (12 weeks)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years and Older
• 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.

• 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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Krankenhaus St. Josef Braunau	Braunau	Oberösterreich	Austria	5280
2	Ordensklinikum Linz GmbH Elisabethinen	Linz	Oberösterreich	Austria	4020
3	Medizinische Universität Graz	Graz	Steiermark	Austria	8036
4	Medizinische Universität Innsbruck	Innsbruck	Tirol	Austria	6020
5	Landeskrankenhaus Feldkirch	Feldkirch	Vorarlberg	Austria	6807
6	Uniklinikum Salzburg - Landeskrankenhaus	Salzburg		Austria	5020
7	Universitätsklinikum AKH Wien	Wien		Austria	1090
8	Klinik Floridsdorf - Krankenhaus Nord	Wien		Austria	1210
9	UZ Leuven Gasthuisberg	Leuven	Vlaams Brabant	Belgium	3000
10	Imeldaziekenhuis - St-Elisabethkliniek	Bonheiden		Belgium	2820
11	AZ St-Jan Brugge Oostende AV	Brugge		Belgium	8000
12	UZ Antwerpen	Edegem		Belgium	2650
13	Jessa Ziekenhuis	Hasselt		Belgium	3500
14	VZW Emmaus	Mechelen		Belgium	2800
15	AZ Delta	Roeselare		Belgium	8800
16	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 3A7
17	Montreal Heart Institute	Montreal	Quebec	Canada	H1T 1C8
18	Clinique Sante Cardio MC	Montreal	Quebec	Canada	H1T 3Y7
19	Institut universitaire de cardiologie et de pneumologie	Ste-Foy	Quebec	Canada	G1V 4G5
20	Fakultni nemocnice Plzen	Plzen		Czechia	304 60
21	Fakultni nemocnice Kralovske Vinohrady	Praha 10		Czechia	100 34
22	Institut Klinicke a Experimentalni Mediciny	Praha 4		Czechia	140 21
23	Fakultni nemocnice v Motole	Praha 5		Czechia	150 06
24	Nemocnice Slany	Slany		Czechia	274 01
25	Krajska nemocnice T. Bati, a.s.	Zlin		Czechia	762 75
26	Hôpital Henri Mondor	Creteil		France	94010
27	Centre Hospitalier Départemental Vendée	La Roche Sur Yon Cedex		France	85025
28	Centre Hospitalier Louis Pasteur	Le Coudray		France	28630
29	Hopital Bichat - Paris	Paris		France	75018
30	Centre Hospitalier Régional - Saint Brieuc	Saint Brieuc		France	22000
31	Hôpital de Rangueil - Toulouse	Toulouse		France	31403
32	Centre Hospitalier - Valenciennes Cedex	Valenciennes Cedex		France	59322
33	Tagore Medical Center	Balatonfured		Hungary	8230
34	University of Semmelweis/ Semmelweis Egyetem	Budapest		Hungary	1122
35	Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz	Budapest		Hungary
36	Kanizsai Dorottya Hospital	Nagykanizsa		Hungary	8800
37	Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.	Nyiregyhaza		Hungary	4400
38	Pecsi Tudomanyegyetem Klinikai Kozpont	Pecs		Hungary	7624
39	Tolna Megyei Balassa Janos Korhaz	Szekszard		Hungary	7100
40	Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz	Szentes		Hungary	6600
41	A.O.U. Policlinico Umberto I	Roma	Lazio	Italy	00161
42	IRCCS Ospedale Policlinico San Martino	Genova	Liguria	Italy	16132
43	ASST Spedali Civili di Brescia	Brescia	Lombardia	Italy	25123
44	ASUR Marche - Area Vasta 5	Ascoli Piceno	Marche	Italy	63074
45	AUSL Toscana Sud-Est	Arezzo	Toscana	Italy	52040
46	AUSL Toscana Sud-Est	Arezzo	Toscana	Italy	52100
47	A.O. di Perugia	Perugia	Umbria	Italy	06132
48	Nakamura Cardiovascular Clinic	Itoshima	Fukuoka	Japan	819-1104
49	Hyogo Brain and Heart Center	Himeji	Hyogo	Japan	670-0981
50	Hayama Heart Center	Miura-gun	Kanagawa	Japan	240-0116
51	Kishiwada Tokushukai Hospital	Kishiwada	Osaka	Japan	596-0042
52	Yao Tokushukai General Hospital	Yao	Osaka	Japan	581-0011
53	Nishiarai Heart Center Hospital	Adachi-ku	Tokyo	Japan	123-0845
54	Minamino Cardiovascular Hospital	Hachioji	Tokyo	Japan	192-0918
55	Tokyo Angel Hospital	Hachioji	Tokyo	Japan	193-0811
56	Koto Hospital	Koto-ku	Tokyo	Japan	136-0072
57	Doctor's Practice in Cardiology	Daugavpils		Latvia	LV-5401
58	Daugavpils Regional Hospital	Daugavpils		Latvia	LV-5417
59	Liepaja Regional Hospital	Liepaja		Latvia	LV-3414
60	1st Riga Clinical Hospital	Riga		Latvia	LV-1001
61	P. Stradins Clinical University Hospital	Riga		Latvia	LV-1002
62	Riga East Clinical University Hospital "Gailezers"	Riga		Latvia	LV-1038
63	Academisch Medisch Centrum (AMC)	Amsterdam		Netherlands	1105 AZ
64	Ziekenhuis Rijnstate	Arnhem		Netherlands	6815 AD
65	Amphia Ziekenhuis, locatie Molengracht	Breda		Netherlands	4818 CK
66	Albert Schweitzer Ziekenhuis, Locatie Dordwijk	Dordrecht		Netherlands	3318 AT
67	Medisch Spectrum Twente	Enschede		Netherlands	7511 JX
68	Martini Ziekenhuis, Locatie van Swieten	Groningen		Netherlands	9728 NT
69	Spaarne Gasthuis - locatie Zuid	Haarlem		Netherlands	2035 RC
70	Maastricht UMC	Maastricht		Netherlands	6229 HX
71	Ciutat Sanitària i Universitària de Bellvitge	L'Hospitalet de Llobregat	Barcelona	Spain	08907
72	Ciutat Sanitària i Universitaria de la Vall d'Hebron	Barcelona		Spain	08035
73	Hospital de la Santa Creu i de Sant Pau	Barcelona		Spain	08041
74	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
75	Hospital Virgen de la Victoria	Málaga		Spain	29010
76	Falu Lasarett	Falun		Sweden	791 82
77	Clemenstorget Hjärtmottagning	Lund		Sweden	222 21
78	Skellefteå Lasarett	Skellefteå		Sweden	931 86
79	Södersjukhuset AB	Stockholm		Sweden	118 83
80	Danderyds sjukhus	Stockholm		Sweden	182 88
81	Avdelningen för kliniska prövningar AKP	Örebro		Sweden	703 62
82	Östersunds Sjukhus	Östersund		Sweden	831 83
83	Kantonsspital Aarau	Aarau	Aargau	Switzerland	5001
84	Universitätsspital Basel	Basel	Basel-Stadt	Switzerland	4031
85	Kantonsspital St. Gallen	St. Gallen	Sankt Gallen	Switzerland	9007
86	Inselspital Universitätsspital Bern	Bern		Switzerland	3010
87	Hôpital Cantonal Universitaire de Genève	Genève		Switzerland	1211
88	Ospedale regionale di Lugano	Lugano		Switzerland	6900
89	Staploe Medical Centre	Ely	Cambridgeshire	United Kingdom	CB7 5SQ
90	Queen Elizabeth II Hospital	Welwyn Garden City	Hertfordshire	United Kingdom	AL7 4HQ
91	Northwick Park Hospital	Harrow	London	United Kingdom	HA1 3UJ
92	St Richard's Hospital	Chichester	West Sussex	United Kingdom	PO19 6SE
93	Heart and Chest Hospital	Liverpool		United Kingdom	L14 3PE

Sponsors and Collaborators

• Bayer

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT04218266
• Other Study ID Numbers: 19765; 2019-002365-35
• First Posted: Jan 6, 2020
• Last Update Posted: Oct 13, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Atrial Fibrillation; Apixaban

Study Results

No Results Posted as of Oct 13, 2021