ADDM Study - Amtrel and Co-Diovan in Type 2 Diabetes Mellitus Hypertension Patients With Microalbuminuria
Condition: Hypertension; Diabetes Mellitus, Type 2; Albuminuria
MeSH terms: Albuminuria; Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of the study is to compare the change from baseline in blood pressures (DBP/SBP)
      to 16-week regimen between Amtrel® and Co-Diovan®. The secondary objectives were listed as
      the following.

        -  To compare the response rate (defined as SBP < 130 mmHg and DBP < 80 mmHg) at the end of
           study

        -  To evaluate the change from baseline in albumin-to-creatinine ratio with
           antihypertensive medications in whole group (combined treatment groups) and each
           treatment group (Amtrel®, Co-Diovan®) at Week 16

        -  The change from baseline in glycosylated hemoglobin (HbA1c) at Week 16

        -  The change from baseline in fasting plasma glucose (FPG) at Week 16

        -  The change from baseline in fasting lipid profiles (triglyceride, total cholesterol,
           high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) at Week 16

        -  The change from baseline in arteriosclerosis marker (brachial-ankle pulse-wave velocity
           (ba-PWV) and ankle-brachial pressure index (ABI), using Colin-VP1000) at Week 16

        -  The change from baseline on the body mass index (BMI) and waist-hip ratio (WHR) at each
           specified study time point

        -  To ascertain the safety and tolerability of Amtrel® versus Co-Diovan® including AE/SAE,
           and laboratory examinations
    

Detailed description: 
      At the screening visit, patients who fulfilled the entrance criteria and had given written
      informed consent entered a placebo running period where they discontinued antihypertensive
      medication for two weeks. During that period, Adalat 5mg could be given for emergency. At the
      end of placebo running period those patients became hypertensive (i.e., SBP between
      130-180mmHg or DBP between 80-110mmHg) were randomized into either treatment group. For those
      patients remaining normotensive continued to be on placebo run-in for another two weeks (10 -
      14 days). After the two-week (10 - 14 days) placebo run-in period those patients became
      hypertensive were randomized into either treatment group. However for those patients
      remaining normotensive were excluded from the study. After randomization into either arm,
      patients entered four months treatment period. The dosage adjustment were proceed in order to
      reach the best effect. During the treatment period there was a monthly visit to assess the
      response of the patients.

      The starting dose of Amtrel® was 1 capsule (contains 1/2 tablet) (amlodipine / benazepril
      hydrochloride 2.5 mg/ 5 mg) every morning and could be adjusted up to 2 capsules (contains 1
      tablet per capsule) (amlodipine / benazepril hydrochloride 10 mg/ 20 mg) every morning if
      patients did not achieve the criteria of SBP<130 mmHg and DBP< 80 mmHg during treatment
      period.

      The starting dose of Co-Diovan® was 1 capsule (contains 1/2 tablet) (valsartan/
      hydrochlorothiazide 40 mg/ 6.25 mg) every morning and could be adjusted up to 2 capsules
      (contains 1 tablet per capsule) (valsartan/ hydrochlorothiazide 160 mg/ 25.0 mg) every
      morning if patients did not achieve the criteria of SBP<130 mmHg and DBP< 80 mmHg during
      treatment period.

      All randomized patients attended monthly clinic visits for the 16-week treatment period. At
      week 4 (Visit 3), all patients were force-titrated to 1 capsule (1 tablet per capsule) for 4
      weeks. Subsequently, those patients did not achieve the target blood pressure (SBP<130 mmHg
      and DBP<80 mmHg) were titrated monthly to next dose level (2 capsule per day).
    

Intervention name(s): Amlodipine+Benazepril; Valsartan+Hydrochlorothiazide
Intervention type(s): Drug; Drug
Intervention description(s): Amlodipine besylate 5 mg + Benazepril hydrochloride 10 mg, daily use and forced titrate till 16-week end; Valsartan 80 mg + Hydrochlorothiazide 12.5 mg, daily use and forced titrate till 16-week end
Other intervention name(s): Amtrel®; Co-Diovan®
Intervention MeSH terms: Amlodipine; Valsartan; Hydrochlorothiazide; Benazepril
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment