The Pediatric Randomized Carvedilol Trial in Children with Heart Failure: rationale and design.
BACKGROUND
Carvedilol is a medication with both beta-receptor and alpha-receptor blocking properties that has been approved for the treatment of heart failure in adults. Little is known about its safety, efficacy, pharmacokinetics, and dosing profile in children.


METHODS
The primary objective of this study is to evaluate the efficacy of carvedilol administered twice daily for 8 months in terms of its effect compared with placebo on a composite measure of clinical outcomes in children with symptomatic systemic ventricular systolic dysfunction and heart failure. The secondary objectives are to determine the effect of carvedilol on individual components of a composite of clinical outcomes (hospitalizations for worsening heart failure, all-cause mortality and cardiovascular hospitalizations, all cause mortality, heart failure symptoms, and patient and physician global assessment); determine the effect of carvedilol on echocardiographic indices of ventricular function and remodeling; characterize the pharmacokinetics of carvedilol in pediatric patients with heart failure; characterize the effects carvedilol on neurohormonal systems; and provide data for the selection of an optimal titration schedule and daily dose of carvedilol in children with heart failure. This study will enroll 150 children between birth and 17 years of age with chronic symptomatic heart failure caused by systemic ventricular systolic dysfunction.


CONCLUSIONS
This study will determine whether carvedilol improves symptoms in children with heart failure as a result of systemic ventricular systolic dysfunction. The study also will provide information on echocardiographic changes of ventricular performance and neurohormonal levels in children with heart failure before and after treatment with carvedilol, in addition to pharmacokinetics of carvedilol in children.
Shaddy
Robert E
RE
University of Utah Health Sciences Center, Salt Lake City, Utah, USA. pcrshadd@ihc.com
Curtin
E Leigh
EL
Sower
Brett
B
Tani
Lloyd Y
LY
Burr
Jeri
J
LaSalle
Bernard
B
Boucek
Mark M
MM
Mahony
Lynn
L
Hsu
Daphne T
DT
Pahl
Elfriede
E
Burch
Grant H
GH
Schlencker-Herceg
Rozsa
R
D000293:Adolescent; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000367:Age Factors; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000077261:Carvedilol; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010919:Placebos; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D016896:Treatment Outcome; D018754:Ventricular Dysfunction / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016276:Ventricular Function / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D010919:Placebos; D011412:Propanolamines; D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain