PROBLEMS OF HOMOGENEITY IN MULTICENTER TRIALS IN HYPERTENSION USING NONINVASIVE AMBULATORY BLOOD-PRESSURE MONITORING

The antihypertensive effects of lisinopril, enalapril and placebo on office and ambulatory blood pressure and heart rate were assessed in a multicentre study carried out in two collaborating clinical centres. At the end of a two week, single-blind, placebo run-in period, 30 outpatients with lying diastolic pressure greater-than-or-equal-to 95 mmHg were treated with lisinopril, enalapril and placebo for four weeks each according to a double-blind, randomised, within-patient design. Twenty-four hour non-invasive ambulatory blood pressure monitoring (Spacelabs ICR 5200) was performed on the last day of each of the three randomised treatment periods. There was no placebo washout between these three periods. The results of the study disclosed an unexpected and statistically significant treatment-centre interaction, which prevented analysis of the pooled data from both trial centres. While Centre 1 found no difference in terms of office and ambulatory blood pressure values between either active treatment and placebo or between the active treatments, Centre 2 found significant differences between both active treatments and placebo and between lisinopril and enalapril. Office and ambulatory blood pressures at the end of run-in were significantly lower in Centre 1 than in Centre 2. These findings indicate that in multicentre clinical trials in hypertension carried out with non-invasive ambulatory blood pressure monitoring, small differences in the study population between centres may produce a significant treatment-centre interaction, which precludes statistical analysis of the pooled results.