Effect of Valsartan Compared to Enalapril on Sitting Systolic Blood Pressure in Children With High Blood Pressure

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00433836
• Collaborator: (none)
• Enrollment: 300
• Locations: 11
• Arms: 6
• Duration (Months): 25
• Patients Per Site: 27.3
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The purpose of this 12-week active controlled trial is to evaluate the safety and efficacy of valsartan 80/160/320 mg (weight stratified) compared with enalapril 10/20/40 mg (weight stratified) on sitting systolic blood pressure (SSBP) in 6 - 17 year old children with hypertension (SSBP ≥ 95th percentile for age gender and height).

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Valsartan; Drug: Enalapril	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Parallel-group, Evaluation of 12 Weeks of Valsartan Compared to Enalapril on Sitting Systolic Blood Pressure in Children 6 to 17 Years of Age With Hypertension
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Valsartan 80 mg	Drug: Valsartan; Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.
Experimental: Valsartan 160 mg	Drug: Valsartan; Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.
Experimental: Valsartan 320 mg	Drug: Valsartan; Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.
Active Comparator: Enalapril 10 mg	Drug: Enalapril; Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.
Active Comparator: Enalapril 20 mg	Drug: Enalapril; Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.
Active Comparator: Enalapril 40 mg	Drug: Enalapril; Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) [Baseline and Week 12]

   Mean sitting systolic blood pressure (MSSBP) change after 12 weeks of treatment measured by office blood pressure measurement.

Secondary Outcome Measures

1. Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) [Baseline and Week 12]

   The change from baseline in mean sitting diastolic blood pressure (MSDBP) after 12 weeks of treatment as measured by office blood pressure.

2. Decrease in MSSBP to < 95th Percentile for Age, Gender and Height [at week 12]

   The percentage of children whose MSSBP decreased to <95th percentile for age, gender, and height on valsartan vs. enalapril monotherapy at week 12.

3. Change From Baseline in Mean Ambulatory Systolic Blood Pressure (ASBP) and Mean Ambulatory Diastolic Blood Pressure (ADBP) Over 24 Hours in Subset of Patients [Baseline and Week 8]

   The effect of valsartan and enalapril between baseline and visit 6 on 24-hour mean ambulatory systolic and diastolic blood pressure (ASBP, ADBP) in a subset of patients.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, ages 6-17, with a documented history of hypertension

• Must be able to swallow a pill

• Must be ≥ 18 kg or ≤160 kg

• MSSBP (mean of 3 measurements) must be ≥ 95th percentile, for age, gender and height, at Visit 2 (randomization), by office blood pressure measurement

• Patients who are eligible and able to participate in the study and whose parent(s)/guardian(s) consent in writing (written informed consent) to their doing so after the purpose and nature of the investigation has been clearly explained to them. (An assent will be required for some patients depending upon their age and local requirements regarding assents)

Exclusion Criteria:

• Renal artery stenosis

• Current diagnosis of heart failure (NYHA Class II-IV).

• MSSBP ≥ 25% above the 95th percentile

• 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.

• 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.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sites in USA	East Hanover	New Jersey	United States	07936
2	Sites in Belgium	Sites in Belgium		Belgium
3	Sites in France	Sites in France		France
4	Sites in Germany	Sites in Germany		Germany
5	Sites in Hungary	Hungary		Hungary
6	Sites in India	Sites in India		India
7	Sites in Italy	Sites in Italy		Italy
8	Sites in Poland	Poland		Poland
9	Sites in Slovakia	Slovakia		Slovakia
10	Sites in Sweden	Sites in Sweden		Sweden	00000
11	Sites in Turkey	Turkey		Turkey

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00433836
• Other Study ID Numbers: CVAL489K2302
• First Posted: Feb 12, 2007
• Last Update Posted: May 19, 2011
• Last Verified: Apr 1, 2011

• Keywords provided by , ,: Children; pediatrics; High Blood Pressure; Hypertension; Valsartan; enalapril
• Additional relevant MeSH terms: Hypertension; Valsartan; Enalapril

Study Results

Participant Flow

Arm/Group Title	Valsartan	Enalapril
Arm/Group Description	Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.	Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.
Period Title: Overall Study
STARTED	151	149
COMPLETED	138	143
NOT COMPLETED	13	6

Baseline Characteristics

Arm/Group Title	Valsartan	Enalapril	Total
Arm/Group Description	Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.	Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.	Total of all reporting groups
Overall Participants	151	149	300
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.7 (2.93)	13.0 (2.94)	12.9 (2.93)
Sex: Female, Male (Count of Participants)
Female	65 43%	44 29.5%	109 36.3%
Male	86 57%	105 70.5%	191 63.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP)
Description	Mean sitting systolic blood pressure (MSSBP) change after 12 weeks of treatment measured by office blood pressure measurement.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat. Only patients who had both baseline and endpoint values are included.

Arm/Group Title	Valsartan	Enalapril
Arm/Group Description	Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.	Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.
Measure Participants	148	148
Least Squares Mean (Standard Error) [mm Hg]	-15.4 (1.29)	-14.1 (1.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Valsartan, Enalapril
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	non-inferiority delta of 3.5 mm Hg
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -3.80 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)
Description	The change from baseline in mean sitting diastolic blood pressure (MSDBP) after 12 weeks of treatment as measured by office blood pressure.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat. Only patients who had both baseline and endpoint values are included.

Arm/Group Title	Valsartan	Enalapril
Arm/Group Description	Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.	Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.
Measure Participants	148	148
Least Squares Mean (Standard Error) [mm Hg]	-9.4 (0.94)	-8.5 (0.95)

3. Secondary Outcome

Title	Decrease in MSSBP to < 95th Percentile for Age, Gender and Height
Description	The percentage of children whose MSSBP decreased to <95th percentile for age, gender, and height on valsartan vs. enalapril monotherapy at week 12.
Time Frame	at week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat. Only patients who had both baseline and endpoint values are included.

Arm/Group Title	Valsartan	Enalapril
Arm/Group Description	Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.	Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.
Measure Participants	148	148
Number [Percentage of participants]	66.9 44.3%	70.3 47.2%

4. Secondary Outcome

Title	Change From Baseline in Mean Ambulatory Systolic Blood Pressure (ASBP) and Mean Ambulatory Diastolic Blood Pressure (ADBP) Over 24 Hours in Subset of Patients
Description	The effect of valsartan and enalapril between baseline and visit 6 on 24-hour mean ambulatory systolic and diastolic blood pressure (ASBP, ADBP) in a subset of patients.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

A subset of approximately 100 - 150 patients from selected centers was expected to undergo Ambulatory Blood Pressure Monitoring at baseline (Week 0) and at Week 8; however, only 56 patients chose to participate in this aspect of the study.

Arm/Group Title	Valsartan	Enalapril
Arm/Group Description	Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.	Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.
Measure Participants	26	30
ASBP	-9.8 (6.75)	-6.8 (7.41)
ADBP	-9.3 (6.27)	-5.5 (5.73)

Adverse Events

Adverse Event Reporting Description	Includes all patients who received at least one dose of post-randomization study drug; patients were analyzed according to the actual treatment received.
Arm/Group Title	Valsartan		Enalapril
Arm/Group Description	Weight stratified dosages given by mouth, once daily, of valsartan 80/160/320 mg.		Weight stratified dosages given by mouth, once daily, of enalapril 10/20/40 mg.
All Cause Mortality
	Valsartan		Enalapril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Valsartan		Enalapril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/151 (2%)		2/148 (1.4%)
Injury, poisoning and procedural complications
Avulsion fracture	0/151 (0%)		1/148 (0.7%)
Renal injury	0/151 (0%)		1/148 (0.7%)
Metabolism and nutrition disorders
Dehydration	1/151 (0.7%)		0/148 (0%)
Hyperkalaemia	1/151 (0.7%)		0/148 (0%)
Nervous system disorders
Brain injury	1/151 (0.7%)		0/148 (0%)
Other (Not Including Serious) Adverse Events
	Valsartan		Enalapril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/151 (27.8%)		52/148 (35.1%)
Infections and infestations
Nasopharyngitis	10/151 (6.6%)		8/148 (5.4%)
Pharyngitis	6/151 (4%)		11/148 (7.4%)
Upper respiratory tract infection	10/151 (6.6%)		7/148 (4.7%)
Nervous system disorders
Headache	18/151 (11.9%)		28/148 (18.9%)
Respiratory, thoracic and mediastinal disorders
Cough	9/151 (6%)		10/148 (6.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.