Clinical trial NCT00129363: Study to Evaluate the Safety of Twice Daily Oral Carvedilol
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Congestive Heart Failure
Keywords: 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
Ventricular Dysfunction/blood
Ventricular Function/drug effects
Ventricular Remodeling/drug effects
Lead sponsor: Shaddy, Robert, M.D.
Sponsor class: INDIV
Collaborators: name: GlaxoSmithKline
First posted: 2005-08-11
Enrollment: 75
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: dose tolerability
measure: growth and development
measure: physical exam (PE) including cardiopulmonary examination
measure: blood pressure (BP), heart rate (HR), height (Ht) and weight [Wt] (including %)
measure: laboratory safety assessments
measure: pregnancy test, if applicable
measure: an echocardiographic measurement
measure: reporting of all adverse events [AEs] (serious and non-serious)
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Mattel Children's Hospital at UCLA
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Boston
country: United States
facility: Children's Hospital, Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Childrens Hospital and Regional Medical Center
state: Washington
Study officials:
affiliation: University of Utah
name: Robert E Shaddy, MD
role: PRINCIPAL_INVESTIGATOR
References: