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

Condition(s) targeted: Hypertension

Intervention: Ramipril (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: King Pharmaceuticals

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.

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

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Blood pressure measured in the principal investigator's clinic before and after 4 weeks of treatment.

Secondary outcome: Safety (adverse events and selected laboratory tests)

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.

Minimum age: 6 Years. Maximum age: 16 Years. Gender(s): Both.

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.

Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

Hospital Interzonal Especializado Materno Infantil, Buenos Aires, Argentina

Centro Infantil del Rínon, Tucomán, Argentina

Hospital General Interzonal "Dr. José Penna", Buenos Aires, Argentina

Hospital de Niños "Dr. Ricardo Gutiérrez", Buenos Aires, Argentina

Hospital de Niños Juan Carlos Navarro, San Juan, Argentina

Clínica Las Condes, Santiago, Chile

Hospital de Niños Roberto del Rio, Santiago, Chile

Hospital Dr. Gustavo Fricke, Vina del Mar, Chile

Hospital Luis Calvo Mackena, Santiago, Chile

Fundación Cardio Infantil - Instituto de Cardiología, Bogotá, Colombia

Instituto Nacional del Riñón, Bogotá, Colombia

Hospital Pablo Tobon Uribe, Medellín, Colombia

Fundación Bios, Barranquilla, Colombia

Hospital Universitario San Vicente de Paul, Medellin, Colombia

Hospital de San Jose, Bogotá, Colombia

Hospital Pablo Tobon Uribe, Medellin, Colombia

Jaslok Hospital and Research Centre, Mumbai, India

Apollo Hospital, Delhi, India

Gujarat Kidney Foundation, Jivraj Mehta Hospital, Ahmedabad, India

St. John's Hospital, Bangalore, India

Institute of Child Health & Hospital for Children, Chennai, India

Heart Care Clinic, Ahmedabad, India

AIl India Institute medical sciences, Delhi, India

Kerala Institute of Medical Science, Trivandrum, India

Apollo Hospital Hyderabad, Hyderabaad, India

KEM Hospital Research Centre, Pune, India

Maulana Azad Medical College and Lok Nayak Hospital, Delhi, India

Christian Medical College and Hospital, Ludhiana, India

Nizam's Institute of Medical Sciences, Hyderabaad, India

Klinika Nefrologii i Dializoterapii, Instytut Centrum Zdrowia Matki Polki, Lodz, Poland

Klinika Nefrologii Pediatrycznej AM, Wroclaw, Poland

I Klinika Chorob Dzieci SPSK nr 1 PAM, Szczecin, Poland

Oddzial Pediatrii i Nefrologii ze Stacja Dializ, Wojewodzki Szpital Dzieciecy, Torun, 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 Transplantacji Nerek, Instytut Pomnik Centrum Zdrowia Dziecka, Warszawa, Poland

Klinika Nefrologii Dzieciecej SPSK nr 1 ACK AMG, Gdansk, Poland

Klinika Kardiologii i Nefrologii Dzieciecej AM, Poznan, Poland

Oddzial Nefrologi Dzieciecej ze Stacja Dializ SSP ZOZ nad Dziecklem i Mlodzieza, Szczecin, Poland

Global Clinical Trial Centre, Port Elizabeth, South Africa

Potchefstroom Medi-Clinic, Potchefstroom, South Africa

Zuid Afrikaans Hospital, Pretoria, South Africa

Jubilee CTC Jubilee Hospital, Pretoria, South Africa

Benmed Park Clinic, Benoni, South Africa

Eastmed Medical centre, Pretoria, South Africa

Pretoria Academic Hospital, Pretoria, South Africa

Chris Hani Baragwanath, Johannesburg, South Africa

Sandton Clinical Research Centre, Sandton, South Africa

Ondokummayis University Medical Faculty Pediatric Nephrology, SAMSUN, Turkey

Dokuzeylul University Medical Faculty Pediatric Nephrology, Izmir, Turkey

Marmara University Medical Faculty Pediatric Nephrology, Istanbul, Turkey

Istanbul University Istanbul Medical Faculty Pediatric Nephrology, Istanbul, Turkey

Vinnitsa National Medical Academy, Department of Hospital Pediatrics on the bases of Regional Pediatric Hospital, Vinnitsa, Ukraine

Dnepropetrovsk Medical Academy, Department of Hospital Pediatrics on the bases of Regional Pediatric Hospital, Dnepropetrovsk, Ukraine

Odessa State Medical University, Dept. of hospital pediatric and neonotology on the bases of Regional Children Hospital, Odessa, Ukraine

Danylo Halytskiy Lviv NationalMedical University, Department of Faculty, Lviv, Ukraine

Institute of Pediatrics and Obstetrics AMS of Ukraine, Department of ecology related health problems, Kyiv, 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

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

Woodland International Research Group, LLC, Little Rock, Arkansas 72211, United States

UAMS College of Medicine/ Arkansas Children's Hospital, Little Rock, Arkansas 72202, United States

Impact Clinical Research, Beverly Hills, California 90211, United States

Neufeld Medical Group, Los Angeles, California 90048, United States

Almon Clinical Research, Inc., Orange, California 92868, United States

Pediatrics in Brevard, Cocoa Beach, Florida 33155, United States

Watson Clinic Center for Research, Inc., Lakeland, Florida 33805, United States

Medical College of Georgia, Augusta, Georgia 30912, United States

Emory University, Atlanta, Georgia 30322, United States

Hawaii Pacific Health, Honolulu, Hawaii 96813, United States

Nephrology and Hypertension Consultants, Park Ridge, Illinois 60068, United States

Tinley Park Pediatric Associates, Tinley Park, Illinois 60477, United States

Kosair Children's Hospital, Louisville, Kentucky 40202, United States

Louisiana State University, Shreveport, Louisiana 71103, United States

Craig Spiegel, MD, Bridgeton, Missouri 63044, United States

Children's Heart Center, Las Vegas, Nevada 89109, United States

Impact Clinical Trials, Las Vegas, Nevada 89106, United States

Premier Clinical Research Group, Toms River, New Jersey 08755, United States

Hartrich Aquino & Hrab, PC, Williamsville, New York 14221, United States

SUNY Upstate Syracuse, Department of Pediatrics, Syracuse, New York 13210, United States

North Carolina Children's and Adults Clinical Research Foundation, Sylva, North Carolina 28779, United States

Western Wake Pediatrics, Cary, North Carolina 27518, United States

Duke Pediatric Clinical Research Program, Durham, North Carolina 27710, United States

University of North Carolina, Chapel Hill, North Carolina 27514, United States

Center for Clinical and Translational Research, Columbus, Ohio 43205, United States

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States

The University of Oklahoma, Tulsa, Oklahoma 74135, United States

Central Sooner Research, Norman, Oklahoma 73069, United States

Northwest Pediatric Kidney Specialists, LLC, Portland, Oregon 97227, United States

Oregon Health and Science University, Portland, Oregon 97201, United States

Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107, United States

Holston Medical Group, Kingsport, Tennessee 37660, United States

Le Bonheur Children's Hospital, Memphis, Tennessee 38105, United States

South East Texas Cardiology Associates, Beaumont, Texas 77701, United States

University of Texas Medical Center, Houston, Texas 77030, United States

University of Utah, Salt Lake City, Utah 84108, United States

Huguenot Pediatrics, Midlothian, Virginia 23113, United States

University of Virginia, Charlottesville, Virginia 22908, United States

Children's Specialty Group, Norfolk, Virginia 23510, United States

Starting date: October 2006
Ending date: November 2007
Last updated: February 8, 2008