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.

Condition	Intervention	Phase
Congestive Heart Failure	Drug: Carvedilol	Phase III

Further Study Details: 

Primary Outcomes: dose tolerability; growth and development; PE including cardiopulmonary examination; BP, HR, Ht and Wt (including %); laboratory safety assessments; pregnancy test, if applicable; an echocardiographic measurement; reporting of all AEs (serious and non-serious)
Expected Total Enrollment:  75

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

Ages Eligible for Study:  up to  17 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. Male or female patients with chronic symptomatic 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.
2. 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:

1. A patient who, in the opinion of the investigator, would not benefit from open-label carvedilol.
2. A patient who, in the opinion of the investigator, is incapable of cooperating with the requirements of this study.

3. 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) -blockers, other than double-blind carvedilol

4. Uncorrected primary obstructive or severe regurgitative valvular disease, nondilated (restrictive) or hypertrophic cardiomyopathy, or significant systemic ventricular outflow obstruction.

5. A patient with any of the following contra-indications to -blocker therapy:

   Heart rate < 2nd percentile for age Unacceptable blood pressures. 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 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

6. 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

7. 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., IUD or oral contraceptives)

8. 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.

California
      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
Colorado
      University of Colorado, Denver,  Colorado,  80218,  United States
Florida
      University of Miami, Miami,  Florida,  33101,  United States
Illinois
      Children''''s Memorial Hospital, Chicago,  Illinois,  60614,  United States
Massachusetts
      Children''''s Hospital, Boston, Boston,  Massachusetts,  02115,  United States
Michigan
      C.S. Mott Children''''s Hospital, Ann Arbor,  Michigan,  48109,  United States
      Children''''s Hospital of Michigan, Detroit,  Michigan,  48201-2196,  United States
Missouri
      Washington University, St. Louis,  Missouri,  63110-1014,  United States
New York
      Columbia University, New York,  New York,  10032-1537,  United States
Pennsylvania
      Children''''s Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
Tennessee
      Vanderbilt Children''''s Hospital, Nashville,  Tennessee,  37332,  United States
Texas
      Texas Children''''s Hospital, Houston,  Texas,  77030,  United States
      UT Southwestern Medical Center, Dallas,  Texas,  75235-7794,  United States
Utah
      University of Utah, Salt Lake City,  Utah,  84132,  United States
Washington
      Seattle Childrens Hospital and Regional Medical Center, Seattle,  Washington,  98105,  United States

Study chairs or principal investigators

Robert E Shaddy, MD,  Principal Investigator,  University of Utah   

Study ID Numbers:  SB 105517-396
Last Updated:  August 10, 2005
Record first received:  August 8, 2005
ClinicalTrials.gov Identifier:  NCT00129363
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-08-23