Extension Study to Assess Long Term Safety, Tolerability, and Efficacy of Valsartan and Enalapril Combined and Alone in Children With Hypertension

An Extension to Study Protocol CVAL489K2302 to Evaluate the Long Term Safety, Tolerability and Efficacy of Valsartan in Children 6 to 17 Years of Age With Hypertension, Versus Enalapril Treatment for 14 Weeks, or Combined With Enalapril Versus Enalapril for 66 Weeks in Chronic Kidney Disease Patients.

The purpose of this extension study is to compare the long-term safety of valsartan versus enalapril, and the effectiveness of the combination of valsartan and enalapril versus enalapril alone in children with hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Valsartan; Drug: Enalapril; Drug: placebo matched to valsartan; Drug: placebo matched to enalapril

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Belgium, Belgium
    • Sites in Belgium
• France
  • France, France
    • Sites in France
• Germany
  • Germany, Germany
    • Sites in germany
• Hungary
  • Hungary, Hungary
    • Sites in Hungary
• India
  • India, India
    • Sites in India
• Italy
  • Italy, Italy
    • Sites in Italy
• Poland
  • Poland, Poland
    • Sites in Poland
• Turkey
  • Turkey, Turkey
    • Sites in Turkey
• United States
  • New Jersey
    • East Hanover, New Jersey, United States, 07936
      • Sites in USA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Successful completion of 12 weeks of double-blind treatment in core protocol CVAL489K2302.
• Patients participating in study CVAL489K2302 who may have discontinued prematurely due to uncontrolled hypertension defined as MSSBP > 20%, but < 25% above the 95th percentile for age, gender, and height after visit 5, qualifies a patient for entry into this extension study.

Exclusion Criteria:

• Renal artery stenosis.
• Current diagnosis of heart failure (NYHA Class II-IV).
• Second or third degree heart block without a pacemaker.
• Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.
• Clinically significant valvular heart disease.
• Patient that demonstrates clinically significant ECG abnormalities other than those associated with left ventricular hypertrophy and AV block controlled with a pacemaker.
• Previous solid organ transplantation except renal, liver or heart transplantation. Renal, liver or heart transplant must have occurred at least 6 months prior to enrollment. Patient must be on stable doses of immunosuppressive therapy for 3 months and deemed clinically stable by the investigator.
• Patients who experienced any adverse events considered serious and drug related in protocol CVAL489K2302.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CKD patients: Valsartan+enalapril	Drug: Valsartan; Valsartan (80, 160, and 320 mg, weight stratified). All study medications were taken orally once daily, at approximately the same time each day, with or without food.; Drug: Enalapril; Enalapril (10, 20, and 40 mg, weight stratified). All study medications were taken orally once daily, at approximately the same time each day, with or without food.
Active Comparator: CKD patients: Enalapril	Drug: Enalapril; Enalapril (10, 20, and 40 mg, weight stratified). All study medications were taken orally once daily, at approximately the same time each day, with or without food.; Drug: placebo matched to valsartan; placebo matched to valsartan. All study medications were taken orally once daily, at approximately the same time each day, with or without food.
Experimental: Non-CKD patients: Valsartan	Drug: Valsartan; Valsartan (80, 160, and 320 mg, weight stratified). All study medications were taken orally once daily, at approximately the same time each day, with or without food.; Drug: placebo matched to enalapril; Placebo matched to enalapril. All study medications were taken orally once daily, at approximately the same time each day, with or without food.
Active Comparator: Non-CKD patients: Enalapril	Drug: Enalapril; Enalapril (10, 20, and 40 mg, weight stratified). All study medications were taken orally once daily, at approximately the same time each day, with or without food.; Drug: placebo matched to valsartan; placebo matched to valsartan. All study medications were taken orally once daily, at approximately the same time each day, with or without food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Patients With Adverse Events	Start of extension (week 13) to end of study (Week 26 in non-CKD patients and Week 50 in CKD patients)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 26	After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using a calibrated standard sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. A negative number indicates lowered blood pressure.	Core Baseline (Week 0) to Week 26
Percentage of Non-CKD Patients Achieving Systolic and Diastolic BP Control at Week 26	Systolic and diastolic blood pressure (BP) control was defined as msSBP and msDBP < 95th percentile for gender, age, and height. After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using a calibrated standard sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit.	Week 26
Change From Baseline in Post-dosing 24-hour Mean Systolic and Diastolic Ambulatory Blood Pressure at Week 20	24-hour ambulatory blood pressure monitoring (ABPM) was conducted once during the extension in a subset of patients at selected centers. For all patients who completed a qualifying ABPM at baseline, an ABPM was to be performed at Week 20. The ABPM monitor was placed on the non-dominant arm.	Core Baseline (Week 0) to Week 20
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 26	After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using a calibrated standard sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. A negative number indicates lowered blood pressure.	Core Baseline (Week 0) to Week 26

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: March 9, 2007
• First Submitted That Met QC Criteria: March 9, 2007
• First Posted (Estimate): March 13, 2007

Study Record Updates

• Last Update Posted (Estimate): July 12, 2011
• Last Update Submitted That Met QC Criteria: June 30, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: pediatrics; children; hypertension; enalapril; high blood pressure; valsartan
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Valsartan; Enalaprilat; Enalapril
• Other Study ID Numbers: CVAL489K2302E1