Study to Evaluate the Safety of Twice Daily Oral Carvedilol

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Shaddy, Robert, M.D.
ClinicalTrials.gov Identifier:
NCT00129363
First received: August 8, 2005
Last updated: December 24, 2008
Last verified: December 2008
  Purpose

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 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open Label Extension Study to Evaluate the Safety of Twice Daily Oral Carvedilol in Pediatric Patients With Chronic Heart Failure

Resource links provided by NLM:


Further study details as provided by Shaddy, Robert, M.D.:

Primary Outcome Measures:
  • 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)

Enrollment: 75
Study Start Date: January 2002
Study Completion Date: January 2006
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
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
  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00129363

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Mattel Children's Hospital at UCLA
Los Angeles, California, United States, 90025
Stanford University
Palo Alto, California, United States, 94303
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80218
United States, Florida
University of Miami
Miami, Florida, United States, 33101
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Massachusetts
Children's Hospital, Boston
Boston, Massachusetts, United States, 02115
United States, Michigan
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201-2196
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110-1014
United States, New York
Columbia University
New York, New York, United States, 10032-1537
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37332
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75235-7794
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
Seattle Childrens Hospital and Regional Medical Center
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Shaddy, Robert, M.D.
GlaxoSmithKline
Investigators
Principal Investigator: Robert E Shaddy, MD University of Utah
  More Information

No publications provided

Responsible Party: Robert E Shaddy, MD, The Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00129363     History of Changes
Other Study ID Numbers: SB 105517-396
Study First Received: August 8, 2005
Last Updated: December 24, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Shaddy, Robert, M.D.:
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
Human
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

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Adrenergic alpha-Antagonists
Carvedilol
Adrenergic beta-Antagonists
Natriuretic Peptide, Brain
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists

ClinicalTrials.gov processed this record on July 22, 2014