Study to Evaluate the Safety of Twice Daily Oral Carvedilol

Study Overview
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Brief Summary
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The objective of this study is to evaluate the long-term safety of carvedilol in pediatric patients with chronic heart failure, who completed the Pediatric Carvedilol Study 321. Carvedilol will be provided as open-label therapy for a period of at least 6 months (or until termination of the study) by SmithKline Beecham Corporation d/b/a GlaxoSmithKline (GSK) or the University Sponsor.

Detailed Description
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This open-label, uncontrolled, extension study is designed to assess the long-term safety of carvedilol in pediatric patients with heart failure and includes the following phases: Screening Phase (coincides with the final maintenance Month 6 Visit in the 321 study Down-/Up-titration Phase Maintenance Phase Down-titration Follow-up

Official Title
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A Multicenter, Open Label Extension Study to Evaluate the Safety of Twice Daily Oral Carvedilol in Pediatric Patients With Chronic Heart Failure

Conditions
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Congestive Heart Failure

Intervention / Treatment
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* Drug: Carvedilol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients with chronic symptomatic congestive heart failure (CHF) due to systemic ventricular systolic dysfunction, who are receiving standard heart failure therapy and have successfully completed the maintenance phase of the Pediatric Carvedilol Study 321. Parent or guardian of patient able and willing to give written informed consent. The written assent from children > 9 years of age is also required. Exclusion Criteria: A patient who, in the opinion of the investigator, would not benefit from open-label carvedilol. A patient who, in the opinion of the investigator, is incapable of cooperating with the requirements of this study. A patient treated with the following medications at the time of entry in the study: Monoamine oxidase (MAO) inhibitors; Calcium entry blockers; α- blockers, or labetalol; Disopyramide, flecainide, encainide, moricizine, propafenone; Intravenous inotropes such as dobutamine or intravenous vasodilator agents such as amrinone or milrinone; Intravenous CHF medications (e.g. diuretics, digoxin); Beta-blockers, other than double-blind carvedilol. Uncorrected primary obstructive or severe regurgitative valvular disease, nondilated (restrictive) or hypertrophic cardiomyopathy, or significant systemic ventricular outflow obstruction. A patient with any of the following contra-indications to beta-blocker therapy: Heart rate < 2nd percentile for age; Unacceptable blood pressure. Sitting (supine in infants) systolic blood pressure must be > 85 mm Hg in teens; >75 mm Hg in school-aged children; and >65 mm Hg in infants; Sick sinus syndrome, second or third degree atrioventricular (AV) block, unless treated with a permanent pacemaker; History or current clinical evidence of moderate-to-severe obstructive pulmonary disease or reactive airway diseases (e.g., asthma) requiring therapy; Unstable insulin-dependent diabetes mellitus. Renovascular hypertension or evidence of pulmonary hypertension (pulmonary vascular resistance index > 6 Wood units m2) unresponsive to vasodilator agents such as oxygen, nitroprusside, or nitric oxide A patient with any one of these general exclusion criteria: Significant renal (serum creatinine > 2.0), hepatic (serum AST and/or ALT > 3 times upper limit of normal), gastrointestinal, or biliary disorders that could impair absorption, metabolism, or excretion of orally administered medications; Endocrine disorders such as pheochromocytoma, active hyperthyroidism and untreated hypothyroidism; Any illness other than heart failure that may limit survival within 1 year (e.g. neoplasm); Girls of childbearing potential who are pregnant or sexually active and not taking adequate contraceptive precautions (e.g., intrauterine device [IUD] or oral contraceptives). A patient who received any investigational drug within the preceding 30 days except blinded medication in Pediatric Carvedilol Study 321. An investigational drug is defined as any agent (placebo or drug) dispensed as part of a research study.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Carvedilol|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dose tolerability |  |  | 
| growth and development |  |  | 
| physical exam (PE) including cardiopulmonary examination |  |  | 
| blood pressure (BP), heart rate (HR), height (Ht) and weight [Wt] (including %) |  |  | 
| laboratory safety assessments |  |  | 
| pregnancy test, if applicable |  |  | 
| an echocardiographic measurement |  |  | 
| reporting of all adverse events [AEs] (serious and non-serious) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human, Adolescent, Adrenergic alpha-Antagonists/therapeutic use, Adrenergic alpha-Antagonists/pharmacokinetics, Adrenergic alpha-Antagonists/administration & dosage, Adrenergic beta-Antagonists/therapeutic use, Adrenergic beta-Antagonists/pharmacokinetics, Adrenergic beta-Antagonists/administration & dosage, Age Factors, Carbazoles/therapeutic use, Carbazoles/administration & dosage, Child, Child, Preschool, Drug Administration Schedule, Female, Heart Failure, Congestive/etiology, Heart Failure, Congestive/drug therapy, Heart Failure, Congestive/blood, Infant, Infant, Newborn, Male, Natriuretic Peptide, Brain/blood, Placebos, Propanolamines/therapeutic use, Propanolamines/administration & dosage, Prospective Studies, Support, Non-U.S. Gov't, Treatment Outcome, Ventricular Dysfunction/drug therapy, Ventricular Dysfunction/complications, Ventricular Dysfunction/blood, Ventricular Function/drug effects, Ventricular Remodeling/drug effects