ADDM Study - Amtrel and Co-Diovan in Type 2 Diabetes Mellitus Hypertension Patients With Microalbuminuria

Condition(s) targeted: Hypertension; Diabetes Mellitus, Type 2; Albuminuria

Intervention: Amlodipine+Benazepril (Drug); Valsartan+Hydrochlorothiazide (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: TSH Biopharm Corporation Limited

Official(s) and/or principal investigator(s):
Wayne H-H Sheu, Principal Investigator, Affiliation: Taichung Veterans General Hospital

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

Official title: Efficacy and Safety of Two Fixed-combination Antihypertensive Regimens, Amtrel® and Co-Diovan® in Type 2 Diabetes Hypertension Patients With Microalbuminuria

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: To compare the change from baseline in blood pressures (DBP/SBP) to 16-week regimen between Amtrel® and Co-Diovan®

Secondary outcome: To compare the response rate (defined as SBP < 130 mmHg and DBP < 80 mmHg) at the end of study

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).

Minimum age: 20 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- type 2 diabetes with stable controlled (HbA1c between 6. 5-10%)

- SBP between 130-180mmHg or DBP between 80-110mmHg

- microalbuminuria (UAE 30-300mg/24hrs or creatinine 30-300mg/g)

Exclusion Criteria:

- IDDM or secondary forms of diabetes

- hepatic and/or renal dysfunction

- serum potassium level > 5. 5mmol/L

- severe renal disease

- Chronic Heart Failure (NYHA class III or IV)

- unstable CV disease

- PTCA within 3 months

Chang Gung Memorial Hospital-Kaohsiung, Kaohsiung 833, Taiwan

Taichung Veterans General Hospital, Taichung 407, Taiwan

Far Eastern Memorial Hospital, Taipei 220, Taiwan

Tri-Service General Hospital, Taipei 114, Taiwan

Starting date: June 2007
Last updated: June 16, 2011