Study design of the Medical Therapy of Prostatic Symptoms (MTOPS) trial.

Alpha-blockers and 5-alpha-reductase inhibitors are medical therapies that are being used as alternatives to surgical interventions to relieve symptoms of benign prostatic hyperplasia (BPH). Taken as monotherapy, alpha-blockers and 5-alpha-reductase inhibitors have each been shown to provide relief from BPH symptoms. Treatment with finasteride over 4 years has been shown to reduce both BPH symptoms and the likelihood of acute urinary retention and the need for surgery. Direct comparison of the alpha-blocker terazosin with finasteride has been done, but only for a period of 1 year. The Medical Therapy of Prostatic Symptoms (MTOPS) trial is a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to evaluate the long-term efficacy of the alpha-blocker doxazosin and the 5-alpha-reductase inhibitor finasteride, whether taken as a monotherapy or in combination, in preventing or delaying the progression of BPH. We describe in this paper the design of the MTOPS trial, the concept of BPH progression, the definition and methods of determining the primary outcome events and the proposed statistical analysis methods. A unique feature of MTOPS is the inclusion of prostate biopsies on a subgroup of randomized participants. Volunteers among randomized participants are to undergo a biopsy of the prostate at predetermined time points during the trial. Studies that will be conducted using the tissue specimens collected in MTOPS can potentially provide information at the molecular level on the natural history of BPH among medically treated and untreated men with moderate to severe symptoms of BPH.