Study to Evaluate the Safety of Twice Daily Oral Carvedilol

Congestive Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00129363
• Other study ID #: SB 105517-396
• Status: Completed
• Phase: Phase 3
• First received: August 8, 2005
• Last updated: December 24, 2008
• Start date: January 2002
• Est. completion date: January 2006

Study information

• Verified date: December 2008
• Source: Shaddy, Robert, M.D.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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:

1. Screening Phase (coincides with the final maintenance Month 6 Visit in the 321 study

2. Down-/Up-titration Phase

3. Maintenance Phase

4. Down-titration

5. Follow-up

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: January 2006
• Est. primary completion date: January 2006
• Gender: Both
• Age group: N/A to 17 Years

Eligibility

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;

• a- 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• Carvedilol

Locations

Country	Name	City	State
United States	C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Hospital, Boston	Boston	Massachusetts
United States	Children's Memorial Hospital	Chicago	Illinois
United States	UT Southwestern Medical Center	Dallas	Texas
United States	University of Colorado	Denver	Colorado
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Mattel Children's Hospital at UCLA	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	Stanford University	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Utah	Salt Lake City	Utah
United States	Seattle Childrens Hospital and Regional Medical Center	Seattle	Washington
United States	Washington University	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Shaddy, Robert, M.D.	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

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