Low-dose Nifedipine-Valsartan Combination Compared to Up-titrated Valsartan Monotherapy in Essential Hypertension

Study Overview
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Brief Summary
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This will be a multi-center, prospective, randomized, open-label, parallel design, two arm comparator trial. In the proposed study, the investigators will compare low-dose combination therapy of Nifedipine GITS/OROS plus Valsartan with up-titrated monotherapy of Valsartan with respect to their blood pressure-decreasing effects in patients with essential hypertension.The study consists of a screening visit, followed by randomization and administration of either Nifedipine GITS/OROS 30 mg in combination with Valsartan 80 mg or Valsartan 160 mg for 12 weeks of treatment.The primary efficacy parameters will be mean SBP and DBP on office BP monitoring at 12 weeks of treatment compared to baseline.

Official Title
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Randomized,Open-label,Parallel Design Comparator Study of Effect of Nifedipine GITS/OROS (Adalat) 30 mg in Combination With Valsartan (Diovan) 80 mg Compared to Valsartan (Diovan) 160 mg Monotherapy in Patients Whose Blood Pressure is Not Well Controlled by Valsartan 80 mg Alone

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Adalat (Nifedipine, BAYA1040)
* Drug: Diovan (Valsartan)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 - 75 years Essential hypertension not well controlled by current low dose (80 mg) valsartan monotherapy for at least 4 weeks. Patients on prior treatment with monotherapy diuretic, ACE-I or beta blocker or an ARB other than valsartan and switched to the current low dose valsartan 80 mg monotherapy for at least 4 weeks are also eligible, provided the hypertension is still not well controlled. Office systolic blood pressure (sitting) >140 mmHg (sitting for >/= 5 min., no cigarettes and/or coffee/tea for >/=30 min. before BP measurement). BMI <33 kg/m2 Exclusion Criteria: Participation in any clinical investigational drug study within the previous 12 weeks Concomitant treatments with: Any anti-hypertensive treatment other than Valsartan 80 mg Cytochrome P450-3A4 inhibitors or inducers Potassium-sparing diuretics Severe hypertension (DBP >/= 110 mm Hg and/or SBP >/= 180 mm Hg) and/or evidence of secondary forms of hypertension Any of the following cardiovascular diseases: History of cardiovascular shock Myocardial infarction or unstable angina within the previous 6 months Severe cardiac valve disease Past or present severe rhythm or conduction disorder. Cerebrovascular ischemic event and/or history of intracerebral hemorrhage or subarachnoid hemorrhage (SAH) within the previous 12 months Type 1 or 2 diabetes mellitus Proteinuria Uncorrected hypokalemia or hyperkalemia, sodium depletion and/or hypovolemia Gastrointestinal disease resulting in the potential for malabsorption and/or severe gastro-intestinal tract narrowing; kock pouch (ileostomy after proctocolectomy) Cholestasis or biliary obstruction Liver disease or aspartate aminotransferase (AST) / alanine aminotransferase (ALT) levels >3 x upper limits of normal (ULN) Renal failure, creatinine level >2.0 mg/dl

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Adalat (Nifedipine, BAYA1040)<br>* Nifedipine GITS/OROS 30 mg OM + Valsartan 80 mg OM<br>|
| Active Comparator: Arm 2<br> | Drug: Diovan (Valsartan)<br>* Valsartan 160 mg OM (Two Valsartan 80mg tablets)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Systolic BP and Diastolic BP on office Blood Pressure monitoring |  | Baseline and 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (>/=10mmHg decrease of office SBP and >/=5mmHg decrease of office DBP) |  | 8 and 12 weeks of treatment | 
| Control rate (</=140/90 of office BP) |  | 8 and 12 weeks of treatment | 
| Change in pulse pressure (difference between SBP and DBP) |  | 12 weeks of treatment | 
| Reduction in Urinary microalbumin excretion(UAE) in patients with microalbuminuria |  | Baseline and 12 weeks of treatment | 
| Adverse Event reporting |  | At the start, every 4 weeks during treatment and at the end of treatment | 
| Vitals signs |  | At the start, every 4 weeks during treatment and at the end of treatment | 
| Laboratory tests |  | At the start and at the end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nifedipine GITS/OROS (Adalat®), Valsartan (Diovan®), Hypertension