Synopsis:We propose a phase II randomized controlled, multi-center, double-blind trial, "The VO2Increase with Testosterone Addition - Heart Failure (VITA-HF) Trial". We plan to enroll 318 patients with chronic HF and NYHA II-III in a 1:1 trial of testosterone therapy (versus placebo): our primary objective is to test the effects on peak VO2 at 26 weeks (a commonly used surrogate outcome in phase II HFRCTthat represents both central and peripheral effects of our interventions). Given the assumptions made (a peak VO2 standard deviation of 2.7 mls/kg/min, paired t-test, and 2-sided alpha 0.05), 318 patients will have 85% power to detect a 1.0 ml/kg/min difference between the groups in the change in peak VO2 over 26 weeks. The minimally clinically important difference for peak VO2 may be as small as 0.26 mls/kg/min but is possibly higher and therefore, we have taken a conservative approach similar to that of other CIHR and NIH trials. Additional measures of quality of life, biomarkers (BNP) and clinical outcomes will be performed at 26 and 52 weeks. Quantitative measurement of core laboratory echocardiographic imaging will also assess the effect on left ventricular remodeling and markers of systolic and diastolic function. Assessment at 26 weeks will allow for the early effects to be demonstrated whereas our secondary endpoint evaluated at 52 weeks will demonstrate clinical and other outcomes important for phase III planning (including clinical, biochemical and echocardiographic endpoints).Androgel 5g was selected due to compliance and prior RCT dosing to ensure efficacy with a broad safety margin.