TRAVERSE (original research)
Trial question
Is testosterone-replacement therapy noninferior to placebo in male patients with hypogonadism and preexisting or a high risk of CVD?
Study design
Multi-center
Double blinded
RCT
Population
5204 male patients.
Inclusion criteria: male patients aged 45-80 years who had preexisting or a high risk of CVD and who reported symptoms of hypogonadism and had 2 fasting testosterone levels < 300 ng/dL.
Key exclusion criteria: congenital or acquired severe hypogonadism; history of prostate cancer or prostate nodules; elevated screening PSA level; thrombophilia; uncontrolled HF.
Interventions
N=2601 testosterone (daily application of transdermal 1.62% gel, dose adjusted to maintain testosterone levels between 350-750 ng/dL).
N=2603 placebo (matching placebo gel daily).
Primary outcome
First occurrence of CV death, nonfatal MI, or nonfatal stroke
7%
7.3%
7.3 %
5.5 %
3.6 %
1.8 %
0.0 %
Testosterone
Placebo
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in first occurrence of CV death, nonfatal MI, or nonfatal stroke (7% vs. 7.3%; HR 0.96, 96% CI 0.78 to 1.17).
Secondary outcomes
No significant difference in first occurrence of CV death, nonfatal MI, nonfatal stroke, or coronary revascularization (10.4% vs. 10.1%; HR 1.02, 95% CI 0.86 to 1.21).
No significant difference in CV death (3.4% vs. 4%; HR 0.84, 95% CI 0.63 to 1.12).
No significant difference in nonfatal MI (2.6% vs. 2.4%; HR 1.1, 95% CI 0.78 to 1.56).
Safety outcomes
No significant differences in adverse and serious adverse event, prostate cancer.
Significant differences in nonfatal arrhythmias warranting intervention (5.2% vs. 3.3%), AF (3.5% vs. 2.4%), AKI (2.3% vs. 1.5%).
Conclusion
In male patients aged 45-80 years who had preexisting or a high risk of CVD and who reported symptoms of hypogonadism and had 2 fasting testosterone levels < 300 ng/dL, testosterone was noninferior to placebo with respect to first occurrence of CV death, nonfatal MI, or nonfatal stroke.
Reference
A Michael Lincoff, Shalender Bhasin, Panagiotis Flevaris et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023 Jul 13;389(2):107-117.
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