A 26-week, prospective, open-label, uncontrolled, multicenter study to evaluate the effect of an escalating-dose regimen of trandolapril on change in blood pressure in treatment-naive and concurrently treated adult hypertensive subjects (TRAIL).
OBJECTIVE
This study evaluated the effectiveness of an escalating-dose regimen of trandolapril in subjects with stage 1 or stage 2 hypertension.


METHODS
This was a 26-week, prospective, open-label,multicenter study in Canadian primary care centers. Subjects with hypertension who were treatment naive or whose disease was uncontrolled on current first-line antihypertensive monotherapy were treated with trandolapril for 26 weeks alone or in addition to their current treatment. Uncontrolled hypertension was defined as systolic/diastolic blood pressure (SBP/DBP) >or=140/90 mm Hg in subjects with no other risk factors or >or=130/80 mm Hg in subjects with diabetes or kidney disease. Trandolapril therapy was initiated at 1 mg/d and was titrated as required to 2 or 4 mg at 4 and 9 weeks after initiation of treatment, respectively, in those not achieving BP targets. At 14 weeks after treatment initiation, subjects not achieving BP targets could receive a combination of trandolapril 4 mg plus a calcium channel blocker (verapamil 240 mg) with or without a diuretic. Primary outcome was the percentage of patients reaching target BP after 14 weeks.


RESULTS
A total of 1683 subjects from 192 general practice clinics across Canada completed the 14-week trandolapril dose-optimization phase, and 1650 completed the full 26-week follow-up. Mean (SD) age was 56.6 (12.6) years, and 49.2% of the subjects were men. At baseline, 82.4% (1359/1650) of subjects were antihypertensive-treatment naive. At the trial end, 73.4% (95% CI, 70.9-75.9) of subjects achieved a target level of SBP/DBP <140/90 mm Hg. The mean (SD) reductions in SBP and DBP were -21.5 (14.0) and -11.9 (9.1) mm Hg, respectively (P < 0.001), and -22.4 (14.0) and -12.7 (9.0) mm Hg, respectively (P < 0.001), at 26 weeks. A total of 343 predominantly mild, nonserious adverse events were attributed to the study drugs, reported by 252 (15.3%) of the 1650 subjects. The most frequently reported nonserious adverse events were cough (6.3%); gastrointestinal disorders (2.3%), predominantly nausea; and headache (2.1%). No serious adverse events were attributed to the study treatment. Trandolapril was generally well tolerated.


CONCLUSIONS
A titration-based, escalating-dose regimen of trandolapril was effective and well tolerated in the management of these subjects who were antihypertensive-treatment naive or whose disease was uncontrolled on a diuretic or a calcium channel blocker in this open-label, uncontrolled, multicenter study. Overall, 73.4% of subjects achieved their target blood pressure goal (<140/90 mm Hg).
Tytus
Richard H
RH
Hamilton Health Sciences, Hamilton, Ontario, Canada.
Burgess
Ellen D
ED
Assouline
Linda
L
Vanjaka
Anita
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002170:Canada; D004232:Diuretics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011320:Primary Health Care; D011446:Prospective Studies; D014700:Verapamil / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D007211:Indoles; C052035:trandolapril; D014700:Verapamil