NCT04142658

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

Terminated Phase 3 Results posted Last updated 20 March 2024

What this trial tests

Phase 3 trial testing Apixaban 5 MG in Aortic Valve Disease in 863 participants. Terminated before completion.

Timeline

1 May 2020

Primary endpoint
12 December 2022

12 December 2022

Quick facts

Lead sponsor	Artivion Inc.
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	863
Start date	1 May 2020
Primary completion	12 December 2022
Estimated completion	12 December 2022
Sites	62 locations across United States

Drugs / interventions tested

• Apixaban 5 MG — full drug profile →
• Apixaban 2.5 MG — full drug profile →
• Warfarin (warfarin) — full drug profile →
• On-X Aortic Mechanical Valve

Conditions studied

• Aortic Valve Disease — all drugs for Aortic Valve Disease →
• Aortic Valve Stenosis — all drugs for Aortic Valve Stenosis →
• Aortic Valve Failure — all drugs for Aortic Valve Failure →

Sponsor

Artivion Inc.

Who can join

18 and older, any sex, with Aortic Valve Disease or Aortic Valve Stenosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Composite of Valve Thrombosis and Valve-related Thromboembolism Primary · through study closure, a median follow-up of 13.5 months

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.

Group	Value	95% CI
Apixaban	20
Warfarin	6

Major Bleeding Primary · through study closure, a median follow-up of 13.5 months

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

Group	Value	95% CI
Apixaban	17
Warfarin	21

Adverse events — posted to ClinicalTrials.gov

Time frame: through study closure, a median follow-up of 13.5 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Apixaban

Serious: 11/433 (3%)

Deaths: 2/433

Warfarin

Serious: 18/430 (4%)

Deaths: 1/430

Serious adverse events (1 terms)

Reaction	System	Apixaban	Warfarin
Major Bleeding	Surgical and medical procedures	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Apixaban	Warfarin
Valve thrombosis or Valve-related thromboembolism	Surgical and medical procedures	—	—

Most-reported serious reactions: Major Bleeding.

Data from ClinicalTrials.gov NCT04142658 adverse events section.

Sponsor's own description

Currently, warfarin is the only approved anticoagulation for patients with mechanical valves. The purpose of this study is to determine if participants with an On-X Prosthetic Heart Valve / On-X aortic valve can be maintained safely and effectively on apixaban. Both the On-X aortic valve and apixaban have been approved for use by the US Food and Drug Administration (FDA) but they have not been approved to be used together.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Rationale and design of PROACT Xa: A randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with a mechanical On-X Aortic Heart Valve.
   Jawitz OK, Wang TY, Lopes RD, Chavez A, et al · · 2020 · cited 63× · PMID 32693197 · DOI 10.1016/j.ahj.2020.06.014
2. Apixaban or Warfarin in Patients with an On-X Mechanical Aortic Valve.
   Wang TY, Svensson LG, Wen J, Vekstein A, et al · · 2023 · cited 60× · PMID 38320162 · DOI 10.1056/evidoa2300067
3. Apixaban Versus Rivaroxaban in Patients With Atrial Fibrillation and Valvular Heart Disease : A Population-Based Study.
   Dawwas GK, Cuker A, Barnes GD, Lewis JD, et al · · 2022 · cited 16× · PMID 36252244 · DOI 10.7326/m22-0318
4. Evolving technology: the TRIFLO tri-leaflet mechanical valve without oral anticoagulation: a potential major innovation in valve surgery.
   Carrel T, Vogt PR, Obrist D, Schaff H. · · 2023 · cited 11× · PMID 37840955 · DOI 10.3389/fcvm.2023.1220633
5. Selection of Non-vitamin K Antagonist Oral Anticoagulant for Stroke Prevention in Atrial Fibrillation Based on Patient Profile: Perspectives from Vietnamese Experts. Part 1.
   Quang Ho TH, Ton MT, Nguyen VL, Pham HM, et al · · 2023 · cited 4× · PMID 38174217 · DOI 10.15420/ecr.2023.24
6. Rapidly Progressive and Catastrophic Calciphylaxis After Mechanical Valve Replacement: An Anticoagulation Dilemma.
   Nyembo PF, Eidman KE, Simegn M, Shaffer AW, et al · · 2022 · cited 3× · PMID 36406917 · DOI 10.1016/j.jaccas.2022.07.034
7. PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation: Part 2: Study results-prostheses, positions, and economic development.
   Jamieson WRE, Ely JL, Brink J, Pennel T, et al · · 2022 · PMID 36590733 · DOI 10.1016/j.xjon.2022.07.011