A Comparison of Indapamide SR 1.5 mg With HCTZ 25 mg, in Combination With an ACE-inhibitor, in Patients With Mild to Moderate AHT and Type 2 DM (AISHA)
Type 2 Diabetes Mellitus
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Comparison of Indapamide SR 1.5 mg With Hydrochlorothiazide 25 mg, in Combination With an ACE-inhibitor, in Patients With Mild to Moderate Hypertension and Type 2 Diabetes Mellitus|
- Better metabolic effects of indapamide SR 1.5 mg+quinapril by comparison with hydrochlorothiazide 25 mg+quinapril, in patients with hypertension and type 2 diabetes mellitus. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Better antihypertensive effects of indapamide SR 1.5 mg+quinapril by comparison with hydrochlorothiazide 25 mg+quinapril, in patients with hypertension and type 2 diabetes mellitus. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Better effects on cardiac and arterial function of indapamide SR 1.5 mg+quinapril by comparison with hydrochlorothiazide 25 mg+quinapril, in patients with hypertension and type 2 diabetes mellitus [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Better safety of indapamide SR 1.5 mg+quinapril by comparison with hydrochlorothiazide 25 mg+quinapril, in patients with hypertension and type 2 diabetes mellitus [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2008|
|Study Completion Date:||August 2010|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
|Active Comparator: Hydrochlorothiazide||
orally, 25 mg, once a day, with Quinapril 10-40 mg, 6 months
Other Name: Nefrix
|Experimental: Indapamide SR||
1.5 mg SR, orally, once a day,with Quinapril 10-40 mg, 6 months
Other Name: Indapamid LPH
Hypertension treatment in patients with type 2 diabetes mellitus is still a difficult clinical problem. New European and American guidelines recommend a target blood pressure of less than 130/80 mmHg. Indeed, it was shown by the Hypertension Optimal Treatment study (HOT study) that reducing diastolic blood pressure to 81 mm Hg instead of 84 mm Hg, the number of major cardiovascular events is reduced by 51%. However, only 25% of the patients with hypertension and diabetes reach the target of 130/80 mm Hg in routine clinical practice. Therefore, combination therapy is always recommended (8, 9). This should include a diuretic; however, none of the two guidelines makes any recommendations regarding which is the best diuretic therapy in hypertensive patients with diabetes.
Indapamide is a diuretic with special characteristics, which was shown in experimental studies to provide cardio- and renal- protection in hypertensive patients. In the same time it has similar antihypertensive effects with amlodipine and hydrochlorothiazide. Intrinsic mechanisms are probably related to the antioxidant properties, and also to the action on the calcium channels. Moreover, when compared with hydrochlorothiazide, indapamide has no adverse effects on lipid metabolism and seems to have no negative impact on the renal function. However, a recent study in patients with hypertension and diabetes suggested no superiority of indapamide over hydrochorothiazide on different metabolic parameters. Therefore, new research looking in more detail to the comparison between the two diuretics is mandatory.
The aim of this study is to evaluate the effects of indapamide SR 1.5 mg on blood pressure, blood tests (glucose metabolism, lipids, minerals, and uric acid), cardiac function, endothelial and arterial function, by comparison with hydrochlorothiazide 25 mg, in patients with hypertension and type 2 diabetes mellitus. In order to achieve a better control of blood pressure in these patients, each diuretic treatments will be added to an ACE inhibitor (quinapril 10-40 mg/day). Therefore, eventually, the study will provide data on the comparison between combination indapamide SR 1.5 mg + quinapril versus hydrochlorothiazide 25 mg + quinapril.
The study will be conducted according to a Prospective, parallel, Randomized, active-controlled, Open, Blinded Endpoint evaluation (PROBE design), in one centre, in at least 50 male and female patients with mild to moderate hypertension and type 2 diabetes mellitus, for a total period of 18 months (12 months of enrollment and 6 months follow-up). Patients who meet the inclusion and exclusion criteria will be randomized 1:1 using a permuted block design. They will receive an ascending number from 1 to 50. The investigator(s) performing and analyzing the echocardiograms, and the central laboratory measuring the BNP blood tests will be blinded to the patient medication.
Patients will be randomized to either indapamide prolonged-release 1.5 mg/day or hydrochlorothiazide 25 mg/day, given orally. Quinapril will be added from the beginning of the study to allow consistent blood pressure control. Dose of quinapril will be titrated from 10 mg/day to 15 mg/day, and then to 20 mg/day, and up to 40 mg/day, as needed for the blood pressure control. The treatment will be administered to randomized patients for 6 months. Assignment of the study medication will be performed through randomization process. The patients will receive the medication from the Investigator/Co-investigator at every visit scheduled; they will be asked to return, at every visit scheduled, the unused medication and the empty boxes, in order to verify their compliance to the treatment. A treatment compliance of 80-120% is considered satisfactory for the study. If compliance is out of the limits mentioned above, the investigator can decide withdrawal of the patient from the study. In exceptional situations, the treatment can be interrupted for a period of maximum 3 days, without withdrawal of the patient from the study. The administration of the study medication will be documented in appropriate source documents and in the CRF and certified by the Investigator.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00980187
|Cardiology, University and Emergency Hospital|
|Bucharest, Romania, 050098|
|Principal Investigator:||Dragos Vinereanu, Professor, MD, PhD||Cardiology, University and Emergency Hospital, Bucharest, Romania|