REVELUTION-2: Relugolix+Abiraterone Acetate (AA) Versus Leuprolide+AA Cardiac Trial

What Was Tested

This registered phase 3 trial tested Leuprolide.

Leuprolide is in a class of medications called gonadotropin-releasing hormone agonists (GNRHa).

It had two arms (groups): Arm I (leuprolide plus abiraterone acetate/prednisone) (experimental) and Arm II (relugolix + abiraterone acetate/prednisone) (experimental).

Patients receive leuprolide IM or SC injections every 3 to 6 months plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy.

Patients receive oral relugolix daily plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy.

The registry classes the interventions as drug, procedure and radiation.

More on the Plan

Identify genomic alterations that predispose an individual to enhanced cardiovascular (CV) toxicity following hormone therapy with leuprolide or relugolix in combination with abiraterone acetate.

Evaluate serum testosterone kinetics during and after treatment with combination leuprolide+AA versus relugolix+AA.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive leuprolide intramuscularly (IM) or subcutaneously (SC) injection every 3 to 6 months plus oral AA with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity.

Who Took Part

Enrollment: 72 planned participants were the target.

It was open to men only aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Men ≥ 18 years old. Plan to undergo curative-intent pelvic radiation therapy (photons or protons) with or without brachytherapy. Plan to undergo up to 24 months of combination androgen deprivation therapy (ADT) plus AA and prednisone.

The full record lists 5 inclusion and 5 exclusion criteria; among the exclusions: prior exposure to androgen deprivation therapy; prior exposure to chemotherapy, immunotherapy, or radiation therapy; history of cardiac bypass surgery or percutaneous coronary intervention.

How the Study Was Run

It was run as a randomized, parallel-group and double-blind study.

The participants were allocated by chance, so the Leuprolide group and the comparison group should start out alike.

Groups ran in parallel: each of the participants stayed in one arm throughout.

Neither the participants nor the staff measuring them knew who was on Leuprolide, so expectations could not easily colour the readings.

Those kept unaware of assignments: investigator and outcomes assessor.

It started in 2025-01-31 with completion listed for 2029-07-01.

It ran at 4 sites in United States (4).

Its stated primary purpose is treatment.

What Was Measured

Researchers chose this as the main measure: Incidence of ambulatory systolic blood pressure (BP) > 140 or diastolic > 90 (measurement on 2 separate days) (time frame: At baseline and up to 12 months). Need for new or escalated anti-hypertensive medication (time frame: At baseline and up to 12 months). Incidence of moderate-to-severe atherosclerosis of major coronary vessels (time frame: From month 0 to month 12).

It also tracked 5 secondary outcomes, for example Total plaque volume, Castration rate, Sustained castration and Testosterone recovery.

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of Leuprolide in 72 people.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Leuprolide compound page, all human trials.