Clinical trial NCT00993109: Low-dose Nifedipine-Valsartan Combination Compared to Up-titrated Valsartan Monotherapy in Essential Hypertension
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: Nifedipine GITS/OROS (Adalat®)
Valsartan (Diovan®)
Hypertension
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2009-10-12
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

  1. Any anti-hypertensive treatment other than Valsartan 80 mg
  2. Cytochrome P450-3A4 inhibitors or inducers
  3. 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

Primary outcomes:
measure: Mean Systolic BP and Diastolic BP on office Blood Pressure monitoring
timeFrame: Baseline and 12 weeks of treatment
Secondary outcomes:
measure: Response rate (>/=10mmHg decrease of office SBP and >/=5mmHg decrease of office DBP)
timeFrame: 8 and 12 weeks of treatment
measure: Control rate (</=140/90 of office BP)
timeFrame: 8 and 12 weeks of treatment
measure: Change in pulse pressure (difference between SBP and DBP)
timeFrame: 12 weeks of treatment
measure: Reduction in Urinary microalbumin excretion(UAE) in patients with microalbuminuria
timeFrame: Baseline and 12 weeks of treatment
measure: Adverse Event reporting
timeFrame: At the start, every 4 weeks during treatment and at the end of treatment
measure: Vitals signs
timeFrame: At the start, every 4 weeks during treatment and at the end of treatment
measure: Laboratory tests
timeFrame: At the start and at the end of treatment
Other outcomes:
Locations:
city: Guangzhou
country: China
state: Guangdong
city: Shijiazhuang
country: China
state: Hebei
city: Changsha
country: China
state: Hunan
city: Changsha
country: China
state: Hunan
city: Nanjing
country: China
state: Jiangsu
city: Nanjing
country: China
state: Jiangsu
city: Shenyang
country: China
state: Liaoning
city: Beijing
country: China
city: Beijing
country: China
city: Shanghai
country: China
city: Donggu,
country: Korea, Republic of
state: Gwangju Gwang''yeogsi
city: Bucheon-si,
country: Korea, Republic of
state: Gyeonggido
city: Yangsan-si
country: Korea, Republic of
state: Gyeongnam
city: Jongno-gu
country: Korea, Republic of
city: Jung-gu
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Ke YN, Dong YG, Ma SP, Yuan H, Ihm SH, Baek SH; ADVISE study group. Improved blood pressure control with nifedipine GITS/valsartan combination versus high-dose valsartan monotherapy in mild-to-moderate hypertensive patients from Asia: results from the ADVISE study, a randomized trial. Cardiovasc Ther. 2012 Dec;30(6):326-32. doi: 10.1111/1755-5922.12003.