Efficacy and Safety of Valsartan/Amlodipine Compared to Amlodipine in Patients With Essential Hypertension

NCT00437645 | Completed Phase 3 Results

• 1 other identifier: CVAA489A2404
• Study Type: interventional
• Target: 1,183
• Locations: 12 countries
• Sites: 12

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.

Conditions

Essential Hypertension

Keywords

Essential hypertension; blood pressure; edema; valsartan; amlodipine; combination treatment

Outcome Measures

Primary Outcomes (2)

• Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8

  Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was \< 0. 5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.

  Baseline to Week 8

• Percentage of Patients With Peripheral Edema From Baseline to Week 8

  Only occurrences of peripheral edema quantified as a reported adverse event coded as peripheral edema were included in the analysis. If a patient experienced more than one occurrence of peripheral edema between Day 1 and Week 8, it was only counted once in the analysis.

  Baseline to Week 8

Secondary Outcomes (3)

• Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8

  Baseline to Week 8

• Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP, msDBP) From Baseline to Weeks 4, 8, and 12

  Baseline to Weeks 4, 8, and 12

• Percentage of Patients Achieving a Systolic Response at Weeks 4, 8, and 12

  Baseline to Weeks 4, 8, and 12

Study Arms (2)

Valsartan/amlodipine 160/5 mg

EXPERIMENTAL

Twelve (12) weeks treatment with the combination of valsartan/amlodipine 160/5 mg. Together with the active medication, patients received a placebo that matched amlodipine 5 mg. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.

Drug: Valsartan 160 mg capsules; Drug: Amlodipine 5 mg capsules; Drug: placebo

Amlodipine 10 mg

ACTIVE COMPARATOR

Eight (8) weeks of treatment with amlodipine 10 mg (two 5 mg capsules). Together with the active medication, the patients received a placebo that matched valsartan 160 mg. At Week 8, patients were switched and treated with the combination of valsartan/amlodipine 160/5 mg and a placebo that matched amlodipine 5 mg for an additional 4 weeks until the end of the study. The three capsules were taken by mouth with water once daily in the morning, regardless of meals. Patients were instructed not to take their study medication the morning of their study visits. Instead, they brought the study medication with them to the site and took it there as instructed by the investigator.

Drug: Valsartan 160 mg capsules; Drug: Amlodipine 5 mg capsules; Drug: placebo

Interventions

Valsartan 160 mg capsules DRUG

Amlodipine 10 mg; Valsartan/amlodipine 160/5 mg

Amlodipine 5 mg capsules DRUG

Amlodipine 10 mg; Valsartan/amlodipine 160/5 mg

placebo DRUG

capsules

Amlodipine 10 mg; Valsartan/amlodipine 160/5 mg

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

sites in Argentina

Agentina, Argentina

Location

sites in Chile

Chile, Chile

Location

sites in Ecuador

Ecuador, Ecuador

Location

sites in Finland

Finland, Finland

Location

sites in France

France, France

Location

sites in Germany

Germany, Germany

Location

sites in Italy

Italy, Italy

Location

sites in Norway

Norway, Norway

Location

sites in Spain

Spain, Spain

Location

sites in Sweden

Sweden, Sweden

Location

sites in Switzerland

Switzerland, Switzerland

Location

sites in Turkey

Turkey, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 19196360 DERIVED

MeSH Terms

Conditions

Essential Hypertension; Edema

Interventions

Valsartan; Amlodipine

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Dihydropyridines; Pyridines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 16, 2007
• First Posted: February 21, 2007
• Study Start: January 1, 2007
• Primary Completion: November 1, 2007
• Study Completion: November 1, 2007
• Last Updated: November 11, 2014
• Results First Posted: February 14, 2011

Record last verified: 2014-11

Locations

AR (1); TU (1); FR (1); IT (1); CL (1); FI (1); NO (1); ES (1); SE (1); CH (1); EC (1); DE (1)