Trial Outcomes & Findings for PROACT Xa - A Trial to Determine if Participants With an On-X Aortic Valve Can be Maintained Safely on Apixaban (NCT NCT04142658)

Last Updated: 2024-03-20

Results Overview

Valve thrombosis was defined as any thrombus, not caused by infection, attached to or near an implanted On-X valve that occluded part of the blood-flow path, interfered with valve function, or was sufficiently large to warrant treatment other than continued oral anticoagulation. Valve-related thromboembolism was defined as any thromboembolic stroke, transient ischemic attack, myocardial infarction, or arterial thromboembolism to an organ or limb that was not associated with infection or an intracardiac tumor and was definitely or possibly related to the valve.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

863 participants

Primary outcome timeframe

through study closure, a median follow-up of 13.5 months

Results posted on

2024-03-20

Participant Flow

Participant milestones

Participant milestones
Measure	Apixaban Apixaban 5 mg twice daily(BID) or 2.5 mg BID Apixaban 5 MG: For patients that do NOT meet the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) Apixaban 2.5 MG: For patients that meet at least 2 of the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.	Warfarin Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0) Warfarin: Active Control Intervention On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.
Overall Study STARTED	433	430
Overall Study COMPLETED	418	400
Overall Study NOT COMPLETED	15	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Apixaban Apixaban 5 mg twice daily(BID) or 2.5 mg BID Apixaban 5 MG: For patients that do NOT meet the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) Apixaban 2.5 MG: For patients that meet at least 2 of the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.	Warfarin Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0) Warfarin: Active Control Intervention On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.
Overall Study Death	2	1
Overall Study Lost to Follow-up	4	13
Overall Study Withdrawal by Subject	9	16

Baseline Characteristics

PROACT Xa - A Trial to Determine if Participants With an On-X Aortic Valve Can be Maintained Safely on Apixaban

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Apixaban n=433 Participants Apixaban 5 mg twice daily(BID) or 2.5 mg BID Apixaban 5 MG: For patients that do NOT meet the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) Apixaban 2.5 MG: For patients that meet at least 2 of the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.	Warfarin n=430 Participants Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0) Warfarin: Active Control Intervention On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.	Total n=863 Participants Total of all reporting groups
Age, Customized	56 years n=5 Participants	55 years n=7 Participants	56 years n=5 Participants
Sex: Female, Male Female	102 Participants n=5 Participants	105 Participants n=7 Participants	207 Participants n=5 Participants
Sex: Female, Male Male	331 Participants n=5 Participants	325 Participants n=7 Participants	656 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants n=5 Participants	20 Participants n=7 Participants	49 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	400 Participants n=5 Participants	406 Participants n=7 Participants	806 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	8 participants n=5 Participants	14 participants n=7 Participants	22 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized White	395 participants n=5 Participants	390 participants n=7 Participants	785 participants n=5 Participants
Race/Ethnicity, Customized Multiracial	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Other	7 participants n=5 Participants	3 participants n=7 Participants	10 participants n=5 Participants
Race/Ethnicity, Customized Unknown	17 participants n=5 Participants	13 participants n=7 Participants	30 participants n=5 Participants
BMI	29.9 kg/m^2 n=5 Participants	30.1 kg/m^2 n=7 Participants	29.9 kg/m^2 n=5 Participants

PRIMARY outcome

Timeframe: through study closure, a median follow-up of 13.5 months

Population: Patient years is determined by the number of events in the Intention to Treat group (all randomized participants) divided by the amount of person-time at risk.

Outcome measures

Outcome measures
Measure	Apixaban n=433 Participants Apixaban 5 mg twice daily(BID) or 2.5 mg BID Apixaban 5 MG: For patients that do NOT meet the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) Apixaban 2.5 MG: For patients that meet at least 2 of the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.	Warfarin n=430 Participants Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0) Warfarin: Active Control Intervention On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.
Composite of Valve Thrombosis and Valve-related Thromboembolism	20 events per patient-years	6 events per patient-years

PRIMARY outcome

Timeframe: through study closure, a median follow-up of 13.5 months

Population: On treatment group

Major bleeding defined as any episode of internal or external bleeding that caused death, hospitalization, or permanent injury or necessitated transfusion, pericardiocentesis, or reoperation.

Outcome measures

Outcome measures
Measure	Apixaban n=420 Participants Apixaban 5 mg twice daily(BID) or 2.5 mg BID Apixaban 5 MG: For patients that do NOT meet the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) Apixaban 2.5 MG: For patients that meet at least 2 of the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.	Warfarin n=414 Participants Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0) Warfarin: Active Control Intervention On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.
Major Bleeding	17 event	21 event

Adverse Events

Apixaban

Serious events: 11 serious events

Other events: 16 other events

Deaths: 2 deaths

Warfarin

Serious events: 18 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Apixaban n=433 participants at risk Apixaban 5 mg twice daily(BID) or 2.5 mg BID Apixaban 5 MG: For patients that do NOT meet the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) Apixaban 2.5 MG: For patients that meet at least 2 of the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.	Warfarin n=430 participants at risk Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0) Warfarin: Active Control Intervention On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.
Surgical and medical procedures Major Bleeding	2.5% 11/433 • Number of events 17 • through study closure, a median follow-up of 13.5 months Events collected and reported were valve thrombosis or dysfunction, stroke or TIA, myocardial infarction, arterial thromboembolism, bleeding, hospitalization and the reason for hospitalization, death and the cause of death.	4.2% 18/430 • Number of events 21 • through study closure, a median follow-up of 13.5 months Events collected and reported were valve thrombosis or dysfunction, stroke or TIA, myocardial infarction, arterial thromboembolism, bleeding, hospitalization and the reason for hospitalization, death and the cause of death.

Other adverse events

Other adverse events
Measure	Apixaban n=433 participants at risk Apixaban 5 mg twice daily(BID) or 2.5 mg BID Apixaban 5 MG: For patients that do NOT meet the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) Apixaban 2.5 MG: For patients that meet at least 2 of the following criteria * age ≥ 80 years * weight ≤ 60 kilograms * creatinine ≥ 1.5 mg/dL (133 micromol/L) On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.	Warfarin n=430 participants at risk Patients randomized to the warfarin arm will continue warfarin in the INR range of (2.0-3.0) Warfarin: Active Control Intervention On-X Aortic Mechanical Valve: Inclusion Criterion: Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.
Surgical and medical procedures Valve thrombosis or Valve-related thromboembolism	3.7% 16/433 • Number of events 20 • through study closure, a median follow-up of 13.5 months Events collected and reported were valve thrombosis or dysfunction, stroke or TIA, myocardial infarction, arterial thromboembolism, bleeding, hospitalization and the reason for hospitalization, death and the cause of death.	1.4% 6/430 • Number of events 6 • through study closure, a median follow-up of 13.5 months Events collected and reported were valve thrombosis or dysfunction, stroke or TIA, myocardial infarction, arterial thromboembolism, bleeding, hospitalization and the reason for hospitalization, death and the cause of death.

Additional Information

Melissa Thalin, Director, New Indications

Artivion

Phone: 770-419-3355

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60