TPS395 Background: Epidemiological studies showed an association between GnRH agonists and a long-term increased risk of CVD, early after treatment initiation and with a higher risk seen in pts with pre-existing CVD. Retrospective pooled safety analyses of 6 randomized trials showed that significantly fewer pts treated with the GnRH receptor antagonists, degarelix, had a CV event or death compared with pts receiving a GnRH receptor agonist. In those studies showing an increased CV risk, Androgen-Deprivation Therapy (ADT) was primarily with GnRH receptor agonists. The mechanistic differences between GnRH antagonists and agonists, including testosterone surge and time to suppression at initiation, effect on follicle-stimulating hormone and on GnRH receptors e.g. T-lymphocytes in atherosclerotic plaque, raises the possibility of different CV risk profiles. The PRONOUNCE trial is the first to prospectively assess whether a GnRH agonist/antagonist can worsen pre-existing CVD; assess the impact of GnRH agonist/antagonist on CV risk biomarkers; and effects of hormonal therapy on immune system. Methods: PRONOUNCE is a multi-center, randomized, controlled trial of 900 men with pc and concomitant CVD, assessing adjudicated MACEs, i.e. myocardial infarction (fatal, non-fatal), stroke (fatal, non-fatal), or death in pts randomized 1:1 to either degarelix or leuprolide according to label recommendations for up to one year. Eligibility include pre-defined CVD, metastatic or locally advanced pc; high-risk disease with plan for definitive radiation therapy (RT); recurrence after local therapy with PSA doubling time <12 months; or salvage RT with neoadjuvant/adjuvant ADT for at least 12 months. Serum samples are collected for the analysis of various CV, inflammatory, and immune biomarkers. The primary endpoint will be based on Kaplan-Meier estimator of survival function and stratified for age group and region. Interim analysis is scheduled when 50% of MACE events have occurred allowing the DSMB to recommend for sample size correction. Clinical trial information: NCT02663908.
Cost-effectiveness of healthy eating and/or physical activity promotion in pregnant women at increased risk of gestational diabetes mellitus: economic evaluation alongside the DALI study, a European multicenter randomized controlled trial
