Clinical trial NCT00389519: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hypertension
Keywords: Hypertension/*etiology
Blood Pressure
Pediatric
Adolescent
Child
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2006-10-19
Enrollment: 422
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline to 4 Weeks in Trough Sitting Systolic Blood Pressure
timeFrame: Baseline to 4 weeks
Secondary outcomes:
measure: Change From Baseline to 4 Weeks in Trough Sitting Diastolic Blood Pressure
timeFrame: Baseline to 4 weeks
measure: Change From Baseline to 4 Weeks in Serum Creatinine
timeFrame: Baseline up to 4 weeks
measure: Change From Baseline to 4 Weeks in Serum Potassium
timeFrame: Baseline up to 4 weeks
measure: Change From Baseline to 4 Weeks in Schwartz Formula Glomerular Filtration Rate (GFR)
timeFrame: Baseline up to 4 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: UAMS College of Medicine/ Arkansas Children's Hospital
state: Arkansas
city: Little Rock
country: United States
facility: Woodland International Research Group, LLC
state: Arkansas
city: Beverly Hills
country: United States
facility: Impact Clinical Research
state: California
city: Los Angeles
country: United States
facility: Neufeld Medical Group
state: California
city: Orange
country: United States
facility: Almon Clinical Research, Inc.
state: California
city: Cocoa Beach
country: United States
facility: Pediatrics in Brevard
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic Center for Research, Inc.
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Health
state: Hawaii
city: Park Ridge
country: United States
facility: Nephrology and Hypertension Consultants
state: Illinois
city: Tinley Park
country: United States
facility: Tinley Park Pediatric Associates
state: Illinois
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University
state: Louisiana
city: Bridgeton
country: United States
facility: Craig Spiegel, MD
state: Missouri
city: Las Vegas
country: United States
facility: Impact Clinical Trials
state: Nevada
city: Las Vegas
country: United States
facility: Children's Heart Center
state: Nevada
city: Toms River
country: United States
facility: Premier Clinical Research Group
state: New Jersey
city: Syracuse
country: United States
facility: SUNY Upstate Syracuse, Department of Pediatrics
state: New York
city: Williamsville
country: United States
facility: Hartrich Aquino & Hrab, PC
state: New York
city: Cary
country: United States
facility: Western Wake Pediatrics
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke Pediatric Clinical Research Program
state: North Carolina
city: Sylva
country: United States
facility: North Carolina Children's and Adults Clinical Research Foundation
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Center for Clinical and Translational Research
state: Ohio
city: Norman
country: United States
facility: Central Sooner Research
state: Oklahoma
city: Tulsa
country: United States
facility: The University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Portland
country: United States
facility: Northwest Pediatric Kidney Specialists, LLC
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Beaumont
country: United States
facility: South East Texas Cardiology Associates
state: Texas
city: Houston
country: United States
facility: University of Texas Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Midlothian
country: United States
facility: Huguenot Pediatrics
state: Virginia
city: Norfolk
country: United States
facility: Children's Specialty Group
state: Virginia
city: Buenos Aires
country: Argentina
facility: Hospital de Niños "Dr. Ricardo Gutiérrez"
city: Buenos Aires
country: Argentina
facility: Hospital General Interzonal "Dr. José Penna"
city: Buenos Aires
country: Argentina
facility: Hospital Interzonal Especializado Materno Infantil
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: San Juan
country: Argentina
facility: Hospital de Niños Juan Carlos Navarro
city: Tucomán
country: Argentina
facility: Centro Infantil del Rínon
city: Santiago
country: Chile
facility: Clínica Las Condes
city: Santiago
country: Chile
facility: Hospital de Niños Roberto del Rio
city: Santiago
country: Chile
facility: Hospital Luis Calvo Mackena
city: Vina del Mar
country: Chile
facility: Hospital Dr. Gustavo Fricke
city: Barranquilla
country: Colombia
facility: Fundación Bios
city: Bogotá
country: Colombia
facility: Fundación Cardio Infantil - Instituto de Cardiología
city: Bogotá
country: Colombia
facility: Hospital de San Jose
city: Bogotá
country: Colombia
facility: Instituto Nacional del Riñón
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Medellin
country: Colombia
facility: Hospital Universitario San Vicente de Paul
city: Medellín
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Ahmedabad
country: India
facility: Gujarat Kidney Foundation, Jivraj Mehta Hospital
city: Ahmedabad
country: India
facility: Heart Care Clinic
city: Bangalore
country: India
facility: St. John's Hospital
city: Chennai
country: India
facility: Institute of Child Health & Hospital for Children
city: Delhi
country: India
facility: AIl India Institute medical sciences
city: Delhi
country: India
facility: Apollo Hospital
city: Delhi
country: India
facility: Maulana Azad Medical College and Lok Nayak Hospital
city: Hyderabaad
country: India
facility: Apollo Hospital Hyderabad
city: Hyderabaad
country: India
facility: Nizam's Institute of Medical Sciences
city: Ludhiana
country: India
facility: Christian Medical College and Hospital
city: Mumbai
country: India
facility: Jaslok Hospital and Research Centre
city: Pune
country: India
facility: KEM Hospital Research Centre
city: Trivandrum
country: India
facility: Kerala Institute of Medical Science
city: Gdansk
country: Poland
facility: Klinika Nefrologii Dzieciecej SPSK nr 1 ACK AMG
city: Katowice
country: Poland
facility: Katedra i Klinika Kardiologii Dzieciecej SK nr 6, Gornoslaskie Centrum Zdrowia Dziecka i Matki, Slaska AM
city: Lodz
country: Poland
facility: II Katedra Pediatrii, Klinika Kardiologii Dzieciecej UM w Lodzi
city: Lodz
country: Poland
facility: Klinika Nefrologii i Dializoterapii, Instytut Centrum Zdrowia Matki Polki
city: Poznan
country: Poland
facility: Klinika Kardiologii i Nefrologii Dzieciecej AM
city: Szczecin
country: Poland
facility: I Klinika Chorob Dzieci SPSK nr 1 PAM
city: Szczecin
country: Poland
facility: Oddzial Nefrologi Dzieciecej ze Stacja Dializ SSP ZOZ nad Dziecklem i Mlodzieza
city: Torun
country: Poland
facility: Oddzial Pediatrii i Nefrologii ze Stacja Dializ, Wojewodzki Szpital Dzieciecy
city: Warszawa
country: Poland
facility: Klinika Nefrologii i Transplantacji Nerek, Instytut Pomnik Centrum Zdrowia Dziecka
city: Wroclaw
country: Poland
facility: Klinika Nefrologii Pediatrycznej AM
city: Benoni
country: South Africa
facility: Benmed Park Clinic
city: Johannesburg
country: South Africa
facility: Chris Hani Baragwanath
city: Port Elizabeth
country: South Africa
facility: Global Clinical Trial Centre
city: Potchefstroom
country: South Africa
facility: Potchefstroom Medi-Clinic
city: Pretoria
country: South Africa
facility: Eastmed Medical centre
city: Pretoria
country: South Africa
facility: Jubilee CTC Jubilee Hospital
city: Pretoria
country: South Africa
facility: Pretoria Academic Hospital
city: Pretoria
country: South Africa
facility: Zuid Afrikaans Hospital
city: Sandton
country: South Africa
facility: Sandton Clinical Research Centre
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty Pediatric Nephrology
city: Istanbul
country: Turkey
facility: Marmara University Medical Faculty Pediatric Nephrology
city: Izmir
country: Turkey
facility: Dokuzeylul University Medical Faculty Pediatric Nephrology
city: Samsun
country: Turkey
facility: Ondokummayis University Medical Faculty Pediatric Nephrology
city: Dnepropetrovsk
country: Ukraine
facility: Dnepropetrovsk Medical Academy, Department of Hospital Pediatrics on the bases of Regional Pediatric Hospital
city: Kharkov
country: Ukraine
facility: Kharkov State University,Dept. of hospital pediatric on the bases of Regional Children's Hospital
city: Kiev
country: Ukraine
facility: NMU n.b. Bogomolets, on b.o. Chil. Clin.Hosp.#2, Department of Pediatrics #2
city: Kyiv
country: Ukraine
facility: Institute of Pediatrics and Obstetrics AMS of Ukraine, Department of ecology related health problems
city: Lviv
country: Ukraine
facility: Danylo Halytskiy Lviv NationalMedical University, Department of Faculty
city: Odessa
country: Ukraine
facility: Odessa State Medical University, Dept. of hospital pediatric and neonotology on the bases of Regional Children Hospital
city: Simferopol
country: Ukraine
facility: Crim.St. Med. Uni. On b.o. Rep. Child.Clin.Hosp. Chair of Pediat. W.c. of Physioth. Of the Postgr.dept
city: Uzhorod
country: Ukraine
facility: Uzhorod National University, Medical faculty, Department of Children's disease with course of Infection disease on the basis of City Children's Clinical Hospital.
city: Vinnitsa
country: Ukraine
facility: Vinnitsa National Medical Academy, Department of Hospital Pediatrics on the bases of Regional Pediatric Hospital
Study officials:
References: