Dose Ranging, Safety and Tolerability of TOPROL-XL® Extended-Release Tablets in Hypertensive Pediatric Subjects
307A
3 other identifiers
interventional
144
2 countries
31
Brief Summary
This was a 4-week, multicenter, double-blind, placebo-controlled, randomized, parallel-group study to determine the antihypertensive dose range, efficacy, safety and tolerability of TOPROL-XL ® (metoprolol succinate) extended-release tablets (metoprolol CR/XL) in hypertensive pediatric subjects. The study population included school age children (age 6 to \< Tanner Stage 3) and adolescents (\> Tanner Stage 3 to age 16) of both genders. No more than 50% of the randomized subjects could be adolescents (\> Tanner Stage 3 to 16 years old). Since response to some therapies in adult hypertension appears to be different in black and non-black populations, recruitment was aimed at a mixture of black and non-black children. The design included a 1-week screening period (for treatment naive subjects), a 1-week single-blind placebo run-in period, and a 4-week double-blind treatment period. Eligible subjects were randomized to the double-blind period with a once daily oral dose of metoprolol CR/XL to one of three target doses: 0.2, 1.0 and 2.0 mg/kg, or placebo. Dosing was weight adjusted. The dose range for this study was 12.5 to 200 mg daily. Subjects were closely monitored and evaluated at the end of Weeks 1, 2, 3 and 4 during the double-blind treatment period.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3 hypertension
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2002
CompletedFirst Submitted
Initial submission to the registry
November 17, 2005
CompletedFirst Posted
Study publicly available on registry
November 21, 2005
CompletedMarch 20, 2007
March 1, 2007
November 17, 2005
March 19, 2007
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To evaluate the dose range, safety, and tolerability of metoprolol CR/XL in hypertensive pediatric subjects, based on the change in sitting SBP from baseline to the end of treatment.
Secondary Outcomes (2)
Slope of placebo-corrected changes in sitting DBP: baseline to end of treatment as a function of target dose. Differences in mean change: baseline to end of treatment comparing each active group to placebo for sitting SBP and DBP.
Safety profile
Interventions
Eligibility Criteria
You may qualify if:
- Male or female between the ages of 6 and 16 years inclusive at the time of screening.
- Have a negative urine pregnancy test, if female of childbearing potential.
- Have a signed informed consent by a parent or a legal guardian and an assent form signed by the subject (if applicable).
- Have hypertension that is either:
- Newly diagnosed and untreated with a mean sitting SBP or DBP above the 95 th percentile on three consecutive office visits, or
- Previously diagnosed and currently treated with antihypertensive therapy at Visit 1, then at Visit 3 (off treatment) have a mean sitting SBP or DBP above the 95 th percentile.
- Have the ability to swallow tablets.
You may not qualify if:
- Have secondary hypertension due to coarctation of aorta, pheochromocytoma, hyperthyroidism or Cushing's syndrome.
- Have SBP or DBP greater than 20 (SBP) or 10 (DBP) mm Hg above the 95th percentile using height adjusted charts for age and gender.
- Have a heart rate \< 55 beats per minute at randomization.
- Have a history of asthma and/or recurring pulmonary disease or infections.
- Have a history of cystic fibrosis.
- Have a known hypersensitivity reaction to beta-blockers.
- Have a known bleeding, coagulation or platelet disorder that can interfere with blood sampling.
- Have a history of Insulin Dependent Diabetes Mellitus.
- Be in any situation or have any condition which, in the opinion of the investigator or sponsor, may interfere with participation in the study or produce a significant risk to the subject or interfere with the assessment of safety and efficacy endpoints.
- Have received any investigational agent for any therapeutic reason within 30 days prior to receiving study medication.
- Have a clinically significant cardiac valvular disease.
- Have a diagnosis of heart failure.
- Have clinically significant arrhythmia. This is defined as any arrhythmia requiring medical therapy or that causes symptoms.
- Atrioventricular (AV) conduction disturbance, ie, second or third degree AV block.
- Be unable or unwilling to comply with the study requirements.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (31)
Research Site
Little Rock, Arkansas, United States
Research Site
Bellflower, California, United States
Research Site
Beverly Hills, California, United States
Research Site
Los Angeles, California, United States
Research Site
Orange, California, United States
Research Site
Hartford, Connecticut, United States
Research Site
Wilmington, Delaware, United States
Research Site
Gainsville, Florida, United States
Research Site
Miami, Florida, United States
Research Site
Orlando, Florida, United States
Research Site
Tampa, Florida, United States
Research Site
Honolulu, Hawaii, United States
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Chicago, Illinois, United States
Research Site
Louisville, Kentucky, United States
Research Site
Livingston, New Jersey, United States
Research Site
New Hyde Park, New York, United States
Research Site
The Bronx, New York, United States
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Durham, North Carolina, United States
Research Site
Winston-Salem, North Carolina, United States
Research Site
Cincinnati, Ohio, United States
Research Site
Cleveland, Ohio, United States
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Columbus, Ohio, United States
Research Site
Landsdale, Pennsylvania, United States
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Philadelphia, Pennsylvania, United States
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Greenville, South Carolina, United States
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Beaumont, Texas, United States
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Houston, Texas, United States
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San Antonio, Texas, United States
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Salt Lake City, Utah, United States
Research Site
Norfolk, Virginia, United States
Research Site
Santo Domingo, Dominican Republic
Related Publications (1)
Batisky DL, Sorof JM, Sugg J, Llewellyn M, Klibaner M, Hainer JW, Portman RJ, Falkner B; Toprol-XL Pediatric Hypertension Investigators. Efficacy and safety of extended release metoprolol succinate in hypertensive children 6 to 16 years of age: a clinical trial experience. J Pediatr. 2007 Feb;150(2):134-9, 139.e1. doi: 10.1016/j.jpeds.2006.09.034.
PMID: 17236889DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
AstraZeneca Toprol Medical Science Director, MD
AstraZeneca
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
Study Record Dates
First Submitted
November 17, 2005
First Posted
November 21, 2005
Study Start
July 1, 2002
Last Updated
March 20, 2007
Record last verified: 2007-03