New design for clinical trial of antihypertensive drugs applied to pindolol, clopamide, and combinations thereof.

A beta-blocker (pindolol) and a diuretic (clopamide) were given in different dosages, singly and in two different combinations, to 71 patients with mild to moderate essential hypertension. The trial design was such that patients took both drugs singly and in combination, and in different doses, according to a set plan. The best regimen for each patient was determined by taking into account not only blood pressure but also resting heart-rate, body-weight, serum potassium, and serum urate. For 19 patients (27%) monotherapy was best--pindolol for 16 and clopamide for 3. For the remaining patients, a combination of pindolol 10 mg and clopamide 5 mg was best for 39, and in 35 of these one tablet daily was sufficient. All patients reached the preset target blood-pressure. The differences in proportions responding best to the following pairs of regimens compared--monotherapy vs combination, and combination of clopamide 5 mg and pindolol 5 mg vs combination of clopamide 5 mg and pindolol 10 mg--were significant (2p less than 0.01). The process by which the best treatment is chosen according to this study design resembles much more closely that followed in general medical practice, than does the process in the conventional hypertension trial, in which only average effects are reported and compared.