Clinical trial NCT01375322: ADDM Study - Amtrel and Co-Diovan in Type 2 Diabetes Mellitus Hypertension Patients With Microalbuminuria
Official title: Efficacy and Safety of Two Fixed-combination Antihypertensive Regimens, Amtrel® and Co-Diovan® in Type 2 Diabetes Hypertension Patients With Microalbuminuria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Diabetes Mellitus, Type 2
Albuminuria
Lead sponsor: TSH Biopharm Corporation Limited
Sponsor class: INDUSTRY
First posted: 2011-06-17
Enrollment: 226
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: To compare the change from baseline in blood pressures (DBP/SBP) to 16-week regimen between Amtrel® and Co-Diovan®
timeFrame: 16-week
Secondary outcomes:
measure: To compare the response rate (defined as SBP < 130 mmHg and DBP < 80 mmHg) at the end of study
timeFrame: 16-week
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital-Kaohsiung
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital
Study officials:
affiliation: Taichung Veterans General Hospital
name: Wayne H-H Sheu
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee IT, Hung YJ, Chen JF, Wang CY, Lee WJ, Sheu WH. Comparison of the efficacy and safety profiles of two fixed-dose combinations of antihypertensive agents, amlodipine/benazepril versus valsartan/hydrochlorothiazide, in patients with type 2 diabetes mellitus and hypertension: a 16-week, multicenter, randomized, double-blind, noninferiority study. Clin Ther. 2012 Aug;34(8):1735-50. doi: 10.1016/j.clinthera.2012.06.014. Epub 2012 Jul 10.