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A Study to Evaluate the Effect of Testosterone Replacement Therapy (TRT) on the Incidence of Major Adverse Cardiovascular Events (MACE) and Efficacy Measures in Hypogonadal Men

Phase 4
Completed
Conditions
Hypogonadism
Cardiovascular Diseases
Interventions
Drug: Placebo
Registration Number
NCT03518034
Lead Sponsor
AbbVie
Brief Summary

This is a double-blinded and placebo-controlled study of topical testosterone replacement therapy (TRT) in symptomatic hypogonadal men with pre-existing cardiovascular disease (CVD) or increased risk for CVD.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
5246
Inclusion Criteria
  • Men between 45 and 80 years age
  • Participants with low serum testosterone concentrations (< 300 ng/dL) who exhibit at least one sign or symptom of hypogonadism and have evidence of cardiovascular (CV) disease or are at an increased risk for CV disease.
Exclusion Criteria
  • Participants with congenital or acquired hypogonadism for whom long-term therapy with placebo would not be medically appropriate
  • Participants with prostate specific antigen (PSA) > 3.0 ng/mL (or 1.5 if on 5-alpha reductase inhibitors)
  • Participants who have been treated with testosterone in the past 6 months and for whom testosterone therapy is contraindicated
  • Confirmed testosterone < 100 ng/dL
  • Body Mass Index (BMI) > 50
  • Hemoglobin A1c (HbA1C) > 11%
  • Hematocrit (Hct) > 50%
  • Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min
  • History of deep vein thrombosis or pulmonary embolism or prostate cancer or heart failure (Class III and IV).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AndroGel 1.62%AndroGel®Participants receive topical testosterone starting with a 40.5 mg dose (2 pump actuations) of the study drug once daily (OD). Participants may receive a dose in the range of 20.25 mg (1 actuation) to 101.25 mg (5 actuations) in 20.25 mg increments during the course of the study if titrations are necessary.
PlaceboPlaceboParticipants receive matching placebo OD.
Primary Outcome Measures
NameTimeMethod
Time From Randomization to the First Component Event of Major Adverse Cardiac Event (MACE): Number and Percentage of Participants With an EventRandomization to event or last known date if no event (up to approximately 52 months)

MACE is a composite endpoint including non-fatal myocardial infraction (MI), non-fatal stroke and cardiovascular (CV) death as adjudicated by Clinical Events Committee (CEC).

Time From Randomization to the First Component Event of MACERandomization to event or last known date if no event (up to approximately 52 months)

MACE is a composite endpoint including non-fatal MI, non-fatal stroke and CV death as adjudicated by CEC.

Secondary Outcome Measures
NameTimeMethod
Incidence of High-Grade Prostate CancerRandomization to event or last known date if no event (up to approximately 52 months).

Presented as the number and percentage of participants with any high grade prostate cancer, defined as Gleason grade of 4 + 3 or higher, as adjudicated by Prostate Safety Events Committee (PAC). This grade is based on how abnormal prostate cells appear. Grade 1: cells look almost like normal prostate cells; Grade 5; cells look very different from normal prostate cells. Since most prostate cancers contain cells of different grades, the 2 most common grades are used. Gleason score is determined by adding the 2 most common grades. Higher numbers indicate a faster growing cancer that is more likely to spread. Currently the lowest score assigned to a tumor is grade 3. Grades below 3 show normal to near normal cells. Most cancers have a Gleason score (the sum of the 2 most common grades) of 6 (Gleason scores of 3+3) or 7 (Gleason scores of 3+4 or 4+3).

Time From Randomization to the First Component Event of CV Safety Endpoint: Number and Percentage of Participants With an EventRandomization to event or last known date if no event (up to approximately 52 months).

The CV safety endpoint is a composite endpoint including non-fatal MI, non-fatal stroke, CV death, and coronary revascularization procedures/cardiac percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) as adjudicated by CEC.

Time From Randomization to the First Component Event of CV Safety EndpointRandomization to event or last known date if no event (up to approximately 52 months).

The CV safety endpoint is a composite endpoint including non-fatal MI, non-fatal stroke, CV death, and coronary revascularization procedures/cardiac PCI, or CABG as adjudicated by CEC.

Trial Locations

Locations (384)

Wright Clinical Research, LLC /ID# 210864

🇺🇸

Alabaster, Alabama, United States

Simon-Williamson Clinic /ID# 210249

🇺🇸

Birmingham, Alabama, United States

Alabama Clinical Therapeutics /ID# 202982

🇺🇸

Birmingham, Alabama, United States

Cahaba Research, Inc. /ID# 167928

🇺🇸

Birmingham, Alabama, United States

Atlanta VAHCS /ID# 170318

🇺🇸

Decatur, Alabama, United States

G & L Research, LLC /ID# 170365

🇺🇸

Foley, Alabama, United States

Fundamental Research /ID# 170504

🇺🇸

Gulf Shores, Alabama, United States

Urology Centers of Alabama /ID# 206197

🇺🇸

Homewood, Alabama, United States

Longwood Research /ID# 201754

🇺🇸

Huntsville, Alabama, United States

Medical Affiliated Research Center, Inc. /ID# 170569

🇺🇸

Huntsville, Alabama, United States

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Wright Clinical Research, LLC /ID# 210864
🇺🇸Alabaster, Alabama, United States
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