A design for testing interventions to improve adherence within a hypertension clinical trial

The Potassium Adherence Clinical Trial (PACT) incorporates one randomized clinical trial within another. A randomized trial of interventions to increase adherence to medication is nested within a second randomized clinical trial testing hypotensive effect of supplemental oral potassium. The trial aims principally to compare the effects of three intervention strategies: two sessions of individual patient counseling, two telephone contacts, or standard care. The trial aims secondarily to evaluate the effect of 60 mEq supplemental oral potassium daily on sitting systolic and diastolic blood pressure in hypertensive patients on established drug therapy. Therefore, it organizes the patients given potassium into three study groups for adherence interventions, and the patients assigned to placebo into a further three. We evaluate adherence primarily by means of the Medication Event Monitoring System (MEMS), an electronic system that records the date and time that the container of study medication is opened. Additional measurements, such as assessments of change in levels of urinary potassium, pill counts, appointment records, self-reporting by patients, and estimates by physician of adherence, are used and correlated with MEMS data. At a single center, the trial enrolled 107 participants between the ages of 26 and 80. This paper describes the background to this trial within a trial, details its design, documents the baseline characteristics of participants enrolled, and describes issues experienced during implementation of the trial.