PACIFIC-AF
Research type
Research Study
Full 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 BAY 2433334 to apixaban in patients with atrial fibrillation.
IRAS ID
272690
Contact name
Gregory Lip
Contact email
Sponsor organisation
Bayer
Eudract number
2019-002365-35
Duration of Study in the UK
1 years, 0 months, 10 days
Research summary
Research Summary
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).
Summary of Results
Researchers are looking for a better way to prevent strokes in people with AF. Before a treatment is available to all patients, researchers study it in trials to better understand its safety and how well it works.
AF is when the upper part of the heart, also called the “atria”, beats abnormally fast and out of sync with the rest of the heart. AF is especially common in elderly people. In people with AF, blood moves through the atria more slowly, which makes it more likely to clump together and form blood clots that can be carried through the bloodstream. This means that people with AF are more likely to have life-threatening medical problems that are caused by blood clots, like strokes.
People with AF can lower their risk of having a stroke by taking a type of drug called an “anti-coagulant” that makes blood less likely to clump and form clots. This type of drug is also known as a “blood thinner”. While anti-coagulants make strokes less likely, they also make severe cases of bleeding more likely. Researchers are trying to make anti-coagulants that do not increase the risk of severe bleeding.
The trial drug, asundexian, is a new anti-coagulant that is designed to prevent strokes in people with AF without causing an increased risk of bleeding. Researchers want to learn more about how asundexian works and how safe it is compared to apixaban. Apixaban is another anti-coagulant that is already approved for use in patients with AF.
The participants were in this trial for up to 16 weeks. But, the entire trial took 1 year and 9 months to finish.
This trial started in January 2020 and ended in October 2021.
The sponsor reviewed the data collected when this trial ended and created a report of the results. This is a summary of that report.What were the results of this trial?
This is a summary of the main results from this trial. The individual results of each participant might be different and are not in this summary.The results from several trials are needed to better understand which treatments work best and are safest. Other trials may provide new information or different results.
There were 2 participants who left this trial before taking any trial treatment. So, the rest of this summary includes results from only 753 participants.Did the participants who took asundexian need medical care for bleeding less often than those who took apixaban?
Yes. Overall, the researchers found that participants who took asundexian needed medical care for bleeding less often than participants who took apixaban.
To answer this question, the researchers kept track of internal and external bleeding that participants had while taking the trial treatments. Researchers were specifically interested in knowing when participants needed additional medical care because of bleeding.
The researchers also looked for cases of “major” bleeding. Major bleeding is when bleeding happens near important body parts or organs, leads to a lot of blood loss, or causes death. None of the participants in this trial had a case of major bleeding.Results are as follows:
How many participants needed medical care for bleeding?
Asundexian 20mg – 1.20% (3)
Asundexian 50mg – 0.39% (1)
Apixaban – 2.40% (6)The researchers also kept track of any type of bleeding that happened during the trial, even if medical care was not needed. The results are summarized below:
How many participants experienced any type of bleeding?
Asundexian 20mg - 4.82% (12)
Asundexian 50mg - 3.94% (10)
Apixaban - 10.40% (26)Most of the cases of bleeding in the table above were “minor” bleeding. Participants with minor bleeding did not need medical care for their bleeding.
Summary of adverse events
The information below is a summary of the adverse events that happened in this trial.How many participants had serious adverse events?
Asundexian 20mg – 8.8% (22)
Asundexian 50mg – 7.9% (20)
Apixaban – 8.0% (20)How many participants had adverse events?
Asundexian 20mg – 47.4% (118)
Asundexian 50mg – 47.2% (120)
Apixaban – 48.8% (122)The most common serious adverse events were:
Heart failure, also known as cardiac failure:
Asundexian 20mg – 1.2% (3)
Asundexian 50mg – 1.6% (4)
Apixaban – 1.2% (3)Atrial Fibrillation
Asundexian 20mg – 1.2% (3)
Asundexian 50mg – 1.2% (3)
Apixaban – 0.8% (2)Stroke, also known as cerebrovascular accident Asundexian 20mg – 0.8% (2) Asundexian 50mg – 0.4% (1) Apixaban – none (0)
The most common adverse events were:
Atrial Fibrillation
Asundexian 20mg – 3.6% (9)
Asundexian 50mg – 3.5% (9)
Apixaban – 3.6% (9)Dizziness
Asundexian 20mg – 3.6% (9)
Asundexian 50mg – 3.1% (8)
Apixaban – 2.8% (7)Nausea
Asundexian 20mg – 2.4% (6)
Asundexian 50mg – 3.1% (8)
Apixaban – 3.6% (9)Summary of adverse reactions
This section is a summary of the medical problems that the participants had during this trial that the doctors reported as possibly related to the trial treatments. These medical problems are called “adverse reactions”. The results from several trials are needed to decide if a treatment causes an adverse reaction.In this trial, the doctors did not know if the participants were taking asundexian or apixaban when medical problems happened.
Some of the adverse reactions listed below are also included in the adverse events above.
This is because the adverse reactions are part of the larger group of adverse events.
Did any adverse reactions happen during this trial?
Below is a summary of adverse reactions that happened in the trial.How many participants had serious adverse reactions?
Asundexian 20mg – 1.6% (4)
Asundexian 50mg – none (0)
Apixaban – none (0)How many participants had adverse reactions?
Asundexian 20mg – 11.6% (29)
Asundexian 50mg – 10.2% (26)
Apixaban – 14.8% (37)How many participants left this trial due to adverse reactions?
Asundexian 20mg – 3.6% (9)
Asundexian 50mg – 2.0% (5)
Apixaban – 2.8% (7)What serious adverse reactions happened during this trial?
The below shows the serious adverse reactions that happened during this trial:Kidneys suddenly stopped working properly, also known as acute kidney injury Asundexian 20mg – 0.4% (1) Asundexian 50mg – none (0) Apixaban – none (0)
Bleeding in the airways, also known as bronchial hemorrhage Asundexian 20mg – 0.4% (1) Asundexian 50mg – none (0) Apixaban – none (0)
Nausea
Asundexian 20mg – 0.4% (1)
Asundexian 50mg – none (0)
Apixaban – none (0)Bleeding in the rectum, also known as rectal hemorrhage Asundexian 20mg – 0.4% (1) Asundexian 50mg – none (0) Apixaban – none (0)
None of the participants died because of a serious adverse reaction during this trial.
What adverse reactions happened during this trial?
The most common adverse reaction was nosebleed, also known as epistaxis.The below shows the adverse reactions that happened during this trial in 5 or more participants. There were other adverse reactions, but those happened in fewer participants.
Nosebleed, also known as epistaxis
Asundexian 20mg – 0.8% (2)
Asundexian 50mg – 2.0% (5)
Apixaban – 4.0% (10)Nausea
Asundexian 20mg – 1.2% (3)
Asundexian 50mg – 2.0% (5)
Apixaban – 1.2% (3)Feeling dizzy
Asundexian 20mg – 1.2% (3)
Asundexian 50mg – 1.2% (3)
Apixaban – 0.8% (2)Diarrhea
Asundexian 20mg – 0.8% (2)
Asundexian 50mg – 0.8% (2)
Apixaban – 0.4% (1)Dry mouth
Asundexian 20mg – 0.8% (2)
Asundexian 50mg – 1.2% (3)
Apixaban – none (0)Blood in the urine, also known as hematuria Asundexian 20mg – 0.4% (1) Asundexian 50mg – none (0) Apixaban – 1.6% (4)
Itching, also known as pruritus
Asundexian 20mg – 1.2% (3)
Asundexian 50mg – 0.8% (2)
Apixaban – none (0)What did the researchers learn from this trial?
This trial helped researchers learn more about how asundexian affects people with AF.The results from several trials are needed to better understand which treatments work best and are safest. This summary only shows the main results from this one trial. Other trials may provide new information or different results.
REC name
North West - Haydock Research Ethics Committee
REC reference
19/NW/0712
Date of REC Opinion
29 Jan 2020
REC opinion
Further Information Favourable Opinion