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
Condition: Hypertension; Type 2 Diabetes Mellitus
MeSH terms: Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Hydrochlorothiazide; Indapamide
Intervention type(s): Drug; Drug
Intervention description(s): orally, 25 mg, once a day, with Quinapril 10-40 mg, 6 months; 1.5 mg SR, orally, once a day,with Quinapril 10-40 mg, 6 months
Other intervention name(s): Nefrix; Indapamid LPH
Intervention MeSH terms: Hydrochlorothiazide; Indapamide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: blood tests; cardiac function; endothelial function; arterial function