Thromb Haemost 2022; 122(06): 1061-1070
DOI: 10.1055/a-1646-2244
Trial Protocol Design Paper

Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in Patients with Provoked Venous Thromboembolism and Enduring Risk Factors: Rationale and Design of the HI-PRO Trial

Behnood Bikdeli
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
3   Center for Outcomes Research and Evaluation, Yale School of Medicine, New Haven, Connecticut, United States
4   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Heather Hogan
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Ruth B. Morrison
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
John Fanikos
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
5   Department of Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Umberto Campia
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Briana M. Barns
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Mariana B. Pfeferman
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Julia E. Snyder
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Candrika D. Khairani
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Samuel Z. Goldhaber
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Gregory Piazza
1   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
› Author Affiliations
Funding The study has been supported by a research grant by Bristol Myers Squibb/Pfizer Alliance. The funders participated in reviewing the study protocol and provided suggestions. Final decisions were left to the discretion of the study principal investigator (G.P.). The funders had no role in the decision to submit the current manuscript.

Abstract

Patients with acute venous thromboembolism (VTE) in the setting of transient provoking factors are typically treated with short-term anticoagulation. However, the risk of recurrence may be increased in the presence of enduring risk factors. In such patients, the optimal duration of treatment remains uncertain. HI-PRO is a single-center, double-blind randomized trial. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) following a major provoking factor, including major surgery or major trauma, who completed at least 3 months of standard-dose therapeutic anticoagulation and have at least one enduring risk factor (such as obesity or heart failure) will be considered for inclusion. Patients will be randomized to apixaban 2.5 mg twice daily or placebo for 12 months. The primary efficacy outcome will be symptomatic recurrent VTE—a composite of DVT and/or PE at 12 months after randomization. Secondary efficacy outcomes include a composite of death due to cardiovascular causes, nonfatal myocardial infarction, stroke or systemic embolism, major adverse limb events, or coronary or peripheral ischemia requiring revascularization at 12 months, and individual components of these outcomes. The primary safety outcome is major bleeding according to the International Society on Thrombosis and Haemostasis definition. The study plans to enroll 600 patients (300 per arm) to have 80% power for detecting a 75% relative risk reduction in the primary outcome. Active recruitment began in March 2021. HI-PRO will provide clinically meaningful data on whether patients with provoked VTE and enduring risk factors have fewer adverse clinical outcomes if prescribed low-intensity extended-duration anticoagulation.



Publication History

Received: 09 August 2021

Accepted: 14 September 2021

Accepted Manuscript online:
16 September 2021

Article published online:
31 October 2021

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