Study to Evaluate the Safety of Twice Daily Oral Carvedilol

Condition(s) targeted: Congestive Heart Failure

Intervention: Carvedilol (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Shaddy, Robert, M.D.

Official(s) and/or principal investigator(s):
Robert E Shaddy, MD, Principal Investigator, Affiliation: University of Utah

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.

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

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study

Primary outcome:

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)

Detailed 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

Minimum age: N/A. Maximum age: 17 Years. Gender(s): Both.

Criteria:

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.

Children's Hospital Los Angeles, Los Angeles, California 90027, United States

Mattel Children's Hospital at UCLA, Los Angeles, California 90025, United States

Stanford University, Palo Alto, California 94303, United States

University of Colorado, Denver, Colorado 80218, United States

University of Miami, Miami, Florida 33101, United States

Children's Memorial Hospital, Chicago, Illinois 60614, United States

Children's Hospital, Boston, Boston, Massachusetts 02115, United States

C.S. Mott Children's Hospital, Ann Arbor, Michigan 48109, United States

Children's Hospital of Michigan, Detroit, Michigan 48201-2196, United States

Washington University, St. Louis, Missouri 63110-1014, United States

Columbia University, New York, New York 10032-1537, United States

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Vanderbilt Children's Hospital, Nashville, Tennessee 37332, United States

Texas Children's Hospital, Houston, Texas 77030, United States

UT Southwestern Medical Center, Dallas, Texas 75235-7794, United States

University of Utah, Salt Lake City, Utah 84132, United States

Seattle Childrens Hospital and Regional Medical Center, Seattle, Washington 98105, United States

Starting date: January 2002
Ending date: January 2006
Last updated: September 6, 2005