A Study of the Effectiveness and Safety of Ramipril in the Treatment of Hypertension in Children and Adolescents

• ClinicalTrials.gov Identifier: NCT00389519
• Recruitment Status: Terminated
• First Posted: October 19, 2006
• Results First Posted: May 19, 2010
• Last Update Posted: June 11, 2012
• Sponsor: Pfizer
• Information provided by: Pfizer

Tracking Information

• First Submitted Date: October 17, 2006
• First Posted Date: October 19, 2006
• Results First Submitted Date: January 21, 2010
• Results First Posted Date: May 19, 2010
• Last Update Posted Date: June 11, 2012
• Study Start Date: October 2006
• Actual Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 29, 2010)

Change From Baseline to 4 Weeks in Trough Sitting Systolic Blood Pressure [ Time Frame: Baseline to 4 weeks ]

Value at end of treatment minus value at baseline, comparing the high-dose ramipril group with placebo

• Original Primary Outcome Measures (submitted: October 18, 2006): Blood pressure measured in the principal investigator's clinic before and after 4 weeks of treatment.

Current Secondary Outcome Measures (submitted: April 29, 2010)

• Change From Baseline to 4 Weeks in Trough Sitting Diastolic Blood Pressure [ Time Frame: Baseline to 4 weeks ]
  Value at end of treatment minus value at baseline, comparing the high-dose ramipril group with placebo
• Change From Baseline to 4 Weeks in Serum Creatinine [ Time Frame: Baseline up to 4 weeks ]
  Value at end of treatment (up to 4 weeks) minus value at baseline
• Change From Baseline to 4 Weeks in Serum Potassium [ Time Frame: Baseline up to 4 weeks ]
  Value at end of treatment (up to 4 weeks) minus value at baseline
• Change From Baseline to 4 Weeks in Schwartz Formula Glomerular Filtration Rate (GFR) [ Time Frame: Baseline up to 4 weeks ]
  Value at end of treatment (up to 4 weeks) minus value at baseline; GFR is a measure of kidney function.

• Original Secondary Outcome Measures (submitted: October 18, 2006): Safety (adverse events and selected laboratory tests)
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of the Effectiveness and Safety of Ramipril in the Treatment of Hypertension in Children and Adolescents
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Arm Study Assessing the Efficacy, Safety, and Dose-Response of Ramipril for the Treatment of Hypertension in Children and Adolescents
• Brief Summary: The primary purpose of this study is to evaluate the blood pressure lowering effects of ramipril, an FDA-approved drug for the treatment of hypertension in adults, in children and adolescents aged 6 to 16 years with hypertension.

Detailed Description

Information is needed on the treatment of hypertension in children and adolescents with antihypertensive drugs like ramipril. The study will assess the safety and blood pressure effects of several doses of the antihypertensive drug ramipril in children and adolescents age 6-16 years. Approximately 450 children will be given placebo, or 1 of the 3 doses of ramipril. The treatment assigned will be done by chance, like flipping a coin. Approximately 120 study centers throughout the world will participate in the trial.

Each child will complete a 1- to 4-week Screening Period where they will stop taking their current blood pressure lowering drug(s), a 4-week Treatment Period where they will receive placebo or one of the ramipril doses, and a Follow-up visit 1 week after completion of the Treatment Period. Children diagnosed with hypertension according to the fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents (U.S. report), will be included in the study if their blood pressure meets certain values.

Each child will complete a minimum of 6 and up to 9 clinic visits over the course of the study during which procedures and assessments of blood pressure and safety will be performed. In addition, a child's parents/guardians will be instructed to measure their child's blood pressure at home between clinic visits.

A planned interim analysis was performed after approximately 240 subjects completed the trial. The study was stopped, as permitted by protocol, after the analysis.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hypertension

Intervention

• Drug: ramipril
  once a day oral ramipril capsules given for 4 weeks
  Other Name: Altace
• Drug: placebo
  once a day oral placebo capsule for 4 weeks

Study Arms

• Placebo Comparator: Placebo
  once per day
  Intervention: Drug: placebo
• Experimental: ramipril low dose
  0.3125, 0.625, or 1.25 mg once a day, based on subject weight
  Intervention: Drug: ramipril
• Experimental: ramipril mid dose
  1.25, 2.5, or 5 mg once a day, based on subject weight
  Intervention: Drug: ramipril
• Experimental: ramipril high dose
  5, 10, or 20 mg once a day, based on subject weight
  Intervention: Drug: ramipril

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 29, 2010): 422
• Original Enrollment (submitted: October 18, 2006): 240
• Actual Study Completion Date: November 2007
• Actual Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Previous, documented diagnosis of hypertension, or newly diagnosed hypertension according to the fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents (United States). SiSBP greater than or equal to the 95th percentile for age, gender, and height.
2. The subject can be safely withdrawn from antihypertensive medications during the screening period, and if given placebo during the treatment period in the judgment of the Investigator.
3. The subject is male or female age 6 to 16 years (inclusive), and weighs greater than or equal to 20 kg.
4. Female subjects greater than or equal to 12 years of age, or who have had greater than or equal to 1 menstruation must: (a) have a negative serum pregnancy test at screening (i.e., subject is not pregnant), (b) not be lactating, and (c) use an acceptable method of contraception.
5. Parents/guardians are able to demonstrate their ability to (a) use a home blood pressure monitor supplied for the study to monitor their child's blood pressure, and (2) mix and administer a liquid dose of study drug if needed.

Exclusion Criteria:

1. Bilateral renal artery stenosis.
2. Uncorrected coarctation of the aorta or corrected coarctation with a right arm/right leg blood pressure gradient greater than 10 mmHg.
3. Severe hypertension.
4. Renal transplantation or other previous solid organ transplantation less than 6 months prior to entering the study.
5. Subjects with nephrotic syndrome not on stable maintenance therapy of prednisone or cyclosporine.
6. A history of cardiomyopathy, clinically significant structural heart disease, or atrioventricular conduction disturbance, sick sinus syndrome, atrial flutter, atrial fibrillation, clinically significant bradycardia or an accessory bypass tract, or clinical symptoms of congestive heart failure.
7. Clinically significant hematologic, hepatobiliary, or renal disease including a Schwartz formula GFR less than 40 mL/min/1.73 m2, and/or serum potassium (K+) greater than 5.5 mEq/L.
8. History of pancreatitis (active or inactive).
9. Known sensitivity to angiotensin converting enzyme inhibitors or a history of angioneurotic edema.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 16 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Chile, Colombia, India, Poland, South Africa, Turkey, Ukraine, United States

Administrative Information

• NCT Number: NCT00389519
• Other Study ID Numbers: K726-06-4003
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: King Pharmaceuticals is now a wholly owned subsidiary of Pfizer
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Pfizer
• Verification Date: June 2012