Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Congestive Heart Failure (PREVENT-CHF): A Phase IIB Randomized Placebo-Controlled Trial

• Register: ClinicalTrials.gov
• Last refreshed on: 4 March 2013
• Main ID: NCT01347970
• Date of registration: 02/05/2011
• Primary sponsor: City of Hope Medical Center
• Public title: Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Congestive Heart Failure (PREVENT-CHF): A Phase IIB Randomized Placebo-Controlled Trial
• Scientific title: Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Congestive Heart Failure (PREVENT-CHF): A Phase IIB Randomized Placebo-Controlled Trial
• Date of first enrolment: May 2012
• Target sample size: 250
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01347970
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Countries of recruitment

Canada, United States

Contacts

• Name: Saro Armenian, DO, MPH
• Affiliation: City of Hope Medical Center

Key inclusion & exclusion criteria

Inclusion Criteria:

- Cancer diagnosis prior to 22 years of age, irrespective of current age

- Lifetime cumulative anthracycline dose: >= 300 mg/m^2

- Time from completion of cancer treatment to study entry: >= 2 years

Exclusion Criteria:

- Receiving treatment for cardiomyopathy or congestive heart failure

- Resting ejection fraction < 50% or fractional shortening < 25%

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

- Low resting systolic blood pressure: < 90 mm hemoglobin (Hg)

- Bradycardia: heart rate < 60 beats per minute (BPM)

- Sustained or symptomatic ventricular dysrhythmias uncontrolled with drug therapy or
implantable device; significant conduction defects (i.e.: second or third degree
atrio-ventricular block or sick sinus syndrome)

- History or current clinical evidence of moderate-to-severe obstructive pulmonary
disease or reactive airway diseases (i.e.: asthma) requiring therapy

- Significant hepatic (serum aspartate aminotransferase [AST] and/or alanine
aminotransferase [ALT] > 3 time upper limit of normal institutional normal),
gastrointestinal, or biliary disorders that could impair absorption, metabolism, or
excretion of orally administered medications

- Endocrine disorders such as primary aldosteronism, pheochromocytoma, hyper- or
hypothyroidism not controlled with medication, or insulin dependent diabetes mellitus

- Females of child bearing potential who are pregnant, lactating, or sexually active
and not taking adequate contraceptive precautions (i.e.: intrauterine device [IUD] or
oral contraceptives for 3 months prior to entry into the study)

- History of drug sensitivity or allergic reaction to alpha- or beta-blockers

- Anemia (hematocrit < 28%)

- Use of an investigational drug or beta adrenergic blockers, including metoprolol,
sotalol, within 30 days of randomization

- Use of select cytochrome P450 2D6 (CYP2D6) inhibitor medications

- Inability to swallow pills

- Unwillingness or inability to cooperate, or, for the parents or guardians of minors,
to give consent, or for the child to give assent, or any condition of sufficient
severity to impair cooperation with the study

- Use of any other blood pressure lowering medication for treatment of hypertension,
within 30 days of randomization



Age minimum: 16 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Cancer Survivor

Intervention(s)

Drug: carvedilol

Genetic: microarray analysis

Genetic: polymerase chain reaction

Genetic: polymorphism analysis

Other: enzyme-linked immunosorbent assay

Other: laboratory biomarker analysis

Other: pharmacogenomic studies

Other: placebo

Other: questionnaire administration

Procedure: quality-of-life assessment

Primary Outcome(s)

LV thickness-dimension ration (LV T-D), reported in terms of LV posterior wall dimension in systole and LV dimension based on the internal diameter in diastole [Time Frame: Up to 24 months]

Secondary Outcome(s)

Blood biomarkers of myocardial remodeling and CHF risk, including cardiac troponins (cTn), blood natriuretic peptide (BNP), and galectin-3 [Time Frame: Up to 24 months]

Echocardiographic efficacy measures, including afterload and systolic and diastolic measurements [Time Frame: Up to 24 months]

Frequency of individuals with elevated liver function measurements (bilirubin, AST, ALT) [Time Frame: Up to 24 months]

Grade 2-4 toxicities, assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [Time Frame: Up to 24 months]

Subjective safety and tolerability measures, including treatment adherence as measured by pill counts and patient reported symptoms [Time Frame: Up to 24 months]

Secondary ID(s)

11018

K12CA001727

NCI-2011-00717

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)