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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00389519
• Other study ID #: K726-06-4003
• Status: Terminated
• Phase: Phase 3
• First received: October 17, 2006
• Last updated: June 6, 2012
• Start date: October 2006
• Est. completion date: November 2007

Study information

• Verified date: June 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBrazil: Ministry of HealthCanada: Health CanadaChile: Instituto de Salud Pública de ChileColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosIndia: Ministry of HealthPoland: Ministry of HealthSouth Africa: Medicines Control CouncilTurkey: Ministry of HealthUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 422
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 16 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

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

Locations

Country	Name	City	State
Argentina	Hospital de Niños "Dr. Ricardo Gutiérrez"	Buenos Aires
Argentina	Hospital General Interzonal "Dr. José Penna"	Buenos Aires
Argentina	Hospital Interzonal Especializado Materno Infantil	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital de Niños Juan Carlos Navarro	San Juan
Argentina	Centro Infantil del Rínon	Tucomán
Chile	Clínica Las Condes	Santiago
Chile	Hospital de Niños Roberto del Rio	Santiago
Chile	Hospital Luis Calvo Mackena	Santiago
Chile	Hospital Dr. Gustavo Fricke	Vina del Mar
Colombia	Fundación Bios	Barranquilla
Colombia	Fundación Cardio Infantil - Instituto de Cardiología	Bogotá
Colombia	Hospital de San Jose	Bogotá
Colombia	Instituto Nacional del Riñón	Bogotá
Colombia	Hospital Pablo Tobon Uribe	Medellin
Colombia	Hospital Universitario San Vicente de Paul	Medellin
Colombia	Hospital Pablo Tobon Uribe	Medellín
India	Gujarat Kidney Foundation, Jivraj Mehta Hospital	Ahmedabad
India	Heart Care Clinic	Ahmedabad
India	St. John's Hospital	Bangalore
India	Institute of Child Health & Hospital for Children	Chennai
India	AIl India Institute medical sciences	Delhi
India	Apollo Hospital	Delhi
India	Maulana Azad Medical College and Lok Nayak Hospital	Delhi
India	Apollo Hospital Hyderabad	Hyderabaad
India	Nizam's Institute of Medical Sciences	Hyderabaad
India	Christian Medical College and Hospital	Ludhiana
India	Jaslok Hospital and Research Centre	Mumbai
India	KEM Hospital Research Centre	Pune
India	Kerala Institute of Medical Science	Trivandrum
Poland	Klinika Nefrologii Dzieciecej SPSK nr 1 ACK AMG	Gdansk
Poland	Katedra i Klinika Kardiologii Dzieciecej SK nr 6, Gornoslaskie Centrum Zdrowia Dziecka i Matki, Slaska AM	Katowice
Poland	II Katedra Pediatrii, Klinika Kardiologii Dzieciecej UM w Lodzi	Lodz
Poland	Klinika Nefrologii i Dializoterapii, Instytut Centrum Zdrowia Matki Polki	Lodz
Poland	Klinika Kardiologii i Nefrologii Dzieciecej AM	Poznan
Poland	I Klinika Chorob Dzieci SPSK nr 1 PAM	Szczecin
Poland	Oddzial Nefrologi Dzieciecej ze Stacja Dializ SSP ZOZ nad Dziecklem i Mlodzieza	Szczecin
Poland	Oddzial Pediatrii i Nefrologii ze Stacja Dializ, Wojewodzki Szpital Dzieciecy	Torun
Poland	Klinika Nefrologii i Transplantacji Nerek, Instytut Pomnik Centrum Zdrowia Dziecka	Warszawa
Poland	Klinika Nefrologii Pediatrycznej AM	Wroclaw
South Africa	Benmed Park Clinic	Benoni
South Africa	Chris Hani Baragwanath	Johannesburg
South Africa	Global Clinical Trial Centre	Port Elizabeth
South Africa	Potchefstroom Medi-Clinic	Potchefstroom
South Africa	Eastmed Medical centre	Pretoria
South Africa	Jubilee CTC Jubilee Hospital	Pretoria
South Africa	Pretoria Academic Hospital	Pretoria
South Africa	Zuid Afrikaans Hospital	Pretoria
South Africa	Sandton Clinical Research Centre	Sandton
Turkey	Istanbul University Istanbul Medical Faculty Pediatric Nephrology	Istanbul
Turkey	Marmara University Medical Faculty Pediatric Nephrology	Istanbul
Turkey	Dokuzeylul University Medical Faculty Pediatric Nephrology	Izmir
Turkey	Ondokummayis University Medical Faculty Pediatric Nephrology	Samsun
Ukraine	Dnepropetrovsk Medical Academy, Department of Hospital Pediatrics on the bases of Regional Pediatric Hospital	Dnepropetrovsk
Ukraine	Kharkov State University,Dept. of hospital pediatric on the bases of Regional Children's Hospital	Kharkov
Ukraine	NMU n.b. Bogomolets, on b.o. Chil. Clin.Hosp.#2, Department of Pediatrics #2	Kiev
Ukraine	Institute of Pediatrics and Obstetrics AMS of Ukraine, Department of ecology related health problems	Kyiv
Ukraine	Danylo Halytskiy Lviv NationalMedical University, Department of Faculty	Lviv
Ukraine	Odessa State Medical University, Dept. of hospital pediatric and neonotology on the bases of Regional Children Hospital	Odessa
Ukraine	Crim.St. Med. Uni. On b.o. Rep. Child.Clin.Hosp. Chair of Pediat. W.c. of Physioth. Of the Postgr.dept	Simferopol
Ukraine	Uzhorod National University, Medical faculty, Department of Children's disease with course of Infection disease on the basis of City Children's Clinical Hospital.	Uzhorod
Ukraine	Vinnitsa National Medical Academy, Department of Hospital Pediatrics on the bases of Regional Pediatric Hospital	Vinnitsa
United States	Emory University	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	South East Texas Cardiology Associates	Beaumont	Texas
United States	Impact Clinical Research	Beverly Hills	California
United States	Craig Spiegel, MD	Bridgeton	Missouri
United States	Western Wake Pediatrics	Cary	North Carolina
United States	University of North Carolina	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Pediatrics in Brevard	Cocoa Beach	Florida
United States	Center for Clinical and Translational Research	Columbus	Ohio
United States	Duke Pediatric Clinical Research Program	Durham	North Carolina
United States	Hawaii Pacific Health	Honolulu	Hawaii
United States	University of Texas Medical Center	Houston	Texas
United States	Holston Medical Group	Kingsport	Tennessee
United States	Watson Clinic Center for Research, Inc.	Lakeland	Florida
United States	Children's Heart Center	Las Vegas	Nevada
United States	Impact Clinical Trials	Las Vegas	Nevada
United States	UAMS College of Medicine/ Arkansas Children's Hospital	Little Rock	Arkansas
United States	Woodland International Research Group, LLC	Little Rock	Arkansas
United States	Neufeld Medical Group	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Huguenot Pediatrics	Midlothian	Virginia
United States	Children's Specialty Group	Norfolk	Virginia
United States	Central Sooner Research	Norman	Oklahoma
United States	Almon Clinical Research, Inc.	Orange	California
United States	Nephrology and Hypertension Consultants	Park Ridge	Illinois
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Northwest Pediatric Kidney Specialists, LLC	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	University of Utah	Salt Lake City	Utah
United States	Louisiana State University	Shreveport	Louisiana
United States	North Carolina Children's and Adults Clinical Research Foundation	Sylva	North Carolina
United States	SUNY Upstate Syracuse, Department of Pediatrics	Syracuse	New York
United States	Tinley Park Pediatric Associates	Tinley Park	Illinois
United States	Premier Clinical Research Group	Toms River	New Jersey
United States	The University of Oklahoma	Tulsa	Oklahoma
United States	Hartrich Aquino & Hrab, PC	Williamsville	New York

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Colombia,  India,  Poland,  South Africa,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to 4 Weeks in Trough Sitting Systolic Blood Pressure	Value at end of treatment minus value at baseline, comparing the high-dose ramipril group with placebo	Baseline to 4 weeks	No
Secondary	Change From Baseline to 4 Weeks in Trough Sitting Diastolic Blood Pressure	Value at end of treatment minus value at baseline, comparing the high-dose ramipril group with placebo	Baseline to 4 weeks	No
Secondary	Change From Baseline to 4 Weeks in Serum Creatinine	Value at end of treatment (up to 4 weeks) minus value at baseline	Baseline up to 4 weeks	Yes
Secondary	Change From Baseline to 4 Weeks in Serum Potassium	Value at end of treatment (up to 4 weeks) minus value at baseline	Baseline up to 4 weeks	Yes
Secondary	Change From Baseline to 4 Weeks in Schwartz Formula Glomerular Filtration Rate (GFR)	Value at end of treatment (up to 4 weeks) minus value at baseline; GFR is a measure of kidney function.	Baseline up to 4 weeks	Yes