Irbesartan in mild to moderate hypertensive patients a phase IV clinical trial

ABSTRACT

This study examines the efficacy of Irbesartan as a potent angiotensin receptor antagonist in achieving the recommended target SBP and DBP in diabetic [<130/80] and non-diabetic patients [<140/90], and the role of adding HCTZ in achieving control of BP in patients not responding adequately to Irbesartan mono-therapy. Moreover, the study emphasizes on the rate of BP control, and analyzes the rate of reduction in different treatment subgroups [Irbesartan 150 mg alone, Irbesartan 300 mg alone, and Irbesartan 300 mg plus HCTZ 12.5 mg]. The study also evaluates the safety profile in each treatment subgroup and the extent of its tolerability as compared to efficacy outcomes. Methods: This multicenter, prospective, open, non-randomized, non-comparative phase IV setting spanned a 3-months [12 weeks] treatment period for each patient, and was preceded by a 7 days prestudy screening period. 1630 subjects were actually enrolled. Each patient was assigned to 5 scheduled visits. The first 3 visits were for dose titration; one visit for follow up and dose maintenance, and a 5th visit for final assessment. The study was considered completed for a patient at the time he/she completed all scheduled study procedures [5 visits]. Patients started on Irbesartan 150 mg, taken orally, once daily with 24 hour interval for 3 weeks; if target BP is not achieved, patient was switched to Irbesartan 300 mg for further 3 weeks; and if target BP was still not achieved, patient was switched to Irbesartan 300 mg plus HCTZ 12.5 mg, for the rest of the study duration. The starting dose and the dose titration schedule were modified according to the Investigator's judgment and patients' BP response. . Results: By the end of the 3 month trial duration [week 12], 91.18% [1324 patients, n= 1452] of the overall ITT population who completed the study reached the target BP irrespective of their treatment subgroup with better BP control for non-diabetic patients, 96.04% [1116 patients, n= 1162] compared to 71.71% [208 patients, n= 290] for diabetics, p<0.001. The percentage of ITT population treated by Irbesartan 150 mg and reached the target blood pressure was 82.7% [81 patients, n= 98] for diabetic patients and 99.0% [500 patients, n=505] among non-diabetics patients, p<0.001. For patients failed to be controlled with Irbesartan 150 mg and treated with Irbesartan 300 mg, the percentage of those reaching the target BP among diabetics was 76.0% [76 patients, n=100] and 96.6% [314 patients, n=325] among non- diabetics, p<0.001. Proportion of enrolled patients reaching a blood pressure target were 55.4% [51 patients, n=92] among diabetics and 90.96% [302 patients, n=332] among non-diabetics for patients treated with Irbesartan 300 mg plus HCTZ 12.5 mg, p<0.001. Irbesartan showed a significant reduction in both mean systolic blood pressure [33.16 mmHg [21.11%], 33.09 mmHg [20.53%], and 29.63 mmg [18.09%] for any Irbesartan 150 mg, 300 mg, and 300 + HCTZ, respectively, p<0.001] and mean diastolic blood pressure [18.61 mmHg [18.98%], 18.42 mmHg [18.61%], and 16.07 mmHg [16.17%] for Irbesartan 150 mg., 300 mg, and 300 + HCTZ, respectively, p<0.001]. That was evident from the third week of treatment throughout the study period till week 12. The percentages of patients that reached the target blood pressure [controlled] were significantly higher in non-diabetics [99% [500], 96.6% [314], and 90.96% [302], for Irbesartan 150 mg, 300 mg, and 300 mg +HCTZ, respectively, p<0.001]compared to diabetics [82.7% [81], 76% [76], and 55.4% [51] for Irbesartan 150 mg, 300 mg, and 300 mg + HCTZ, respectively, p<0.001] for each of the Irbesartan strengths