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

Phase 4

Completed

• Conditions: Hypertension; Diabetes Mellitus, Type 2; Albuminuria
• Interventions: Drug: Valsartan+Hydrochlorothiazide; Drug: Amlodipine+Benazepril

• Registration Number: NCT01375322
• Lead Sponsor: TSH Biopharm Corporation Limited

Brief 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).

Study Timeline

• Study Start: 2007-06
• Primary Completion: 2010-06
• Study Completion: 2010-06
• Status Verified: 2011-06
• Study First Submitted: 2011-06-15
• Study First Submitted QC: 2011-06-16
• Last Update Submitted: 2011-06-16
• Study First Posted: 2011-06-17
• Last Update Posted: 2011-06-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 226

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Co-Diovan® Group	Valsartan+Hydrochlorothiazide	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
Amtrel® Group	Amlodipine+Benazepril	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
To compare the response rate (defined as SBP < 130 mmHg and DBP < 80 mmHg) at the end of study	16-week

Trial Locations

Locations (4)

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

Tri-Service General Hospital; 🇨🇳 Taipei, Taiwan

Far Eastern Memorial Hospital; 🇨🇳 Taipei, Taiwan

Chang Gung Memorial Hospital-Kaohsiung; 🇨🇳 Kaohsiung, Taiwan