Clinical trial NCT00437645: Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension
Official title: A Double-blind, Randomized, Multicenter, Parallel Group Study to Evaluate the Efficacy, Tolerability, and Safety of Treatment With the Combination of Valsartan/Amlodipine 160/5 mg Compared to Amlodipine 10 mg in Patients With Essential Hypertension Not Adequately Controlled With Amlodipine 5 mg Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Essential Hypertension
Keywords: Essential hypertension
blood pressure
edema
valsartan
amlodipine
combination treatment
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-02-21
Enrollment: 1183
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was designed to compare the efficacy, tolerability, and safety of the combination valsartan/amlodipine 160/5 mg versus amlodipine 10 mg in patients with essential hypertension not adequately controlled (defined as mean sitting systolic blood pressure \[msSBP\] ≥ 130 mmHg and ≤ 160 mmHg) on amlodipine 5 mg alone. The study evaluated both the efficacy and tolerability of the treatments by providing data that assessed blood pressure and the proportion of patients developing peripheral edema.


Eligibility criteria: Inclusion Criteria:

* Male or female outpatients ≥ 55 years of age
* Patients with essential hypertension measured using a validated automated oscillometric device at Visit 1
* Non-treated patients must have a MSSBP ≥ 140 mmHg and ≤ 160 mmHg
* Patients pre-treated on monotherapy prior to Visit 1 must have MSSBP ≤ 160 mmHg
* To be eligible for randomization at Visit 2 (Day 1) all patients must have a MSSBP ≥ 130 mmHg and ≤ 160 mmHg
* No peripheral edema at Visit 2 (randomization)
* Written informed consent to participate in this study prior to any study procedures

Exclusion Criteria:

* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant
* Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers, calcium channel blockers, or to drugs with similar chemical structures
* Patients taking more than 1 antihypertensive medication at Visit 1
* Administration of any agent indicated for the treatment of hypertension after Visit 1 with the exception of pre-treated patients that require tapering down of anti-hypertensive treatments. For patients with previous antihypertensive medication that require a gradual downward titration, the tapering down should be done according to manufacturers instructions and last dose should be taken by week -2 prior to randomization
* msSBP \> 180 mmHg or msDBP \> 110 mmHg at any time between Visit 1 and Visit 2
* Evidence of a secondary form of hypertension, including but not limited to any of the following: Coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's disease, polycystic kidney disease, or pheochromocytoma
* History of hypertensive encephalopathy, cerebrovascular accident, transient ischemic attack, myocardial infarction, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) 12 months prior to Visit 1
* History of heart failure Grade II - IV according to the NYHA classification
* Second or third degree heart block with or without a pacemaker
* Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia
* Concomitant unstable angina pectoris
* Clinically significant valvular heart disease
* Patients with Type 1 diabetes mellitus
* Patients with Type 2 diabetes mellitus who are not well controlled based on the investigator's judgment. It is recommended that Type 2 diabetic patients are adequately controlled and, if treated with medication, be on a stable dose of oral anti-diabetic medication for at least 4 weeks prior to Visit 1
* Evidence of hepatic disease as determined by one of the following: AST or ALT values \> 2x UNL at study entry, a history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt
* Evidence of renal impairment as determined by one of the following: serum creatinine \> 1.5 x UNL at visit 1, history of dialysis, or history of nephrotic syndrome
* Serum potassium values \> 5.5 mmol/L at study entry
* Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug
* Any surgical or medical condition which, at the discretion of the investigator or Novartis medical monitor, places the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study period
* Volume depletion based on the investigator's clinical judgment using vital signs, skin turgor, moistness of mucous membranes, and laboratory values
* Any severe, life-threatening disease within the past five years
* History of drug or alcohol abuse within the last 2 years
* Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
* Inability to communicate and comply with all study requirements including the unwillingness or inability to provide informed consent
* Persons directly involved in the execution of this protocol

Primary outcomes:
measure: Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8
timeFrame: Baseline to Week 8
measure: Percentage of Patients With Peripheral Edema From Baseline to Week 8
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8
timeFrame: Baseline to Week 8
measure: Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12
timeFrame: Baseline to Weeks 4, 8, and 12
measure: Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12
timeFrame: Baseline to Weeks 4, 8, and 12
Other outcomes:
Locations:
city: Agentina
country: Argentina
facility: sites in Argentina
city: Chile
country: Chile
facility: sites in Chile
city: Ecuador
country: Ecuador
facility: sites in Ecuador
city: Finland
country: Finland
facility: sites in Finland
city: France
country: France
facility: sites in France
city: Germany
country: Germany
facility: sites in Germany
city: Italy
country: Italy
facility: sites in Italy
city: Norway
country: Norway
facility: sites in Norway
city: Spain
country: Spain
facility: sites in Spain
city: Sweden
country: Sweden
facility: sites in Sweden
city: Switzerland
country: Switzerland
facility: sites in Switzerland
city: Turkey
country: Turkey
facility: sites in Turkey
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_CHAIR
References:
citation: Schrader J, Salvetti A, Calvo C, Akpinar E, Keeling L, Weisskopf M, Brunel P. The combination of amlodipine/valsartan 5/160 mg produces less peripheral oedema than amlodipine 10 mg in hypertensive patients not adequately controlled with amlodipine 5 mg. Int J Clin Pract. 2009 Feb;63(2):217-25. doi: 10.1111/j.1742-1241.2008.01977.x.