NCT02717507 · REGISTRY CONDITION SEARCH

Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2025-04-23

This phase IIb trial studies how well low-dose carvedilol works in preventing heart failure in cancer survivors exposed to high dose anthracyclines for management of childhood cancer. Patients who received high-dose anthracycline chemotherapy are at a much greater risk for developing heart failure compared to survivors who didn't get any anthracycline chemotherapy. Heart failure happens when the heart muscle has been weakened and can't pump blood as well as it should. Carvedilol may help lower the risk of cardiovascular complications.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz)

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outcome · POSTED

Average Left Ventricular End-systolic Wall Stress

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outcome · POSTED

Average Left Ventricular End-systolic Dimension

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outcome · POSTED

Average Left Ventricular End-systolic Volume

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outcome · POSTED

Average Left Ventricular End-diastolic Dimension

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outcome · POSTED

Average Left Ventricular End-diastolic Volume

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outcome · POSTED

Average Left Ventricular Mass

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outcome · POSTED

Average Fractional Shortening

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outcome · POSTED

Average Ejection Fraction

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outcome · POSTED

Average Peak Early Atrial Divided by Peak Late Atrial Velocities

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outcome · POSTED

Average N-terminal Pro B-type Natriuretic Peptide

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outcome · POSTED

Average Cardiac N-terminal Pro B-type Natriuretic Peptide

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outcome · POSTED

Average Cardiac Troponin I

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outcome · POSTED

Average Galectin-3

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outcome · POSTED

Proportion of Patients With Reportable Adverse Events as Described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).

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outcome · POSTED

Average Bilirubin

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outcome · POSTED

Average Aspartate Aminotransferase

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outcome · POSTED

Average Alanine Aminotransferase

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outcome · POSTED

Proportion of Participants With Average Adherence > 90%

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outcome · POSTED

Proportion of Patients Who Responded "Moderately", "Quite a Bit", or "Extremely" to the Question of How Bothersome the Listed Symptom Was at Any Post-day 0 Assessment Time Point.

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Males and females must weigh \>= 40 Kg * Patient must have had a cancer diagnosis \< 22 years of age, irrespective of current age * Patient must have a lifetime cumulative anthracycline dose of \>= 250 mg/m\^2 DOXOrubicin equivalent without the protection of dexrazoxane (Zinecard) therapy; the anthracycline dose threshold must be met as part of the treatment of a cancer that was diagnosed at \< 22 years of age * Note: Institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) can be used to document lifetime receipt of anthracycline dose * Patient must have completed cancer treatment \>= 2 years prior to study enrollment Exclusion Criteria: * Receiving treatment for cardiomyopathy or heart failure * Ejection fraction of \< 50% (by radionuclide angiogram or echocardiogram) or shortening fraction of \< 25% (by echocardiogram) * Note: for instances where both are reported, and one is below the threshold, the site will have the option to re-measure it centrally at the core lab * Uncorrected primary obstructive or severe regurgitative valvular disease: * Nondilated (restrictive); or * Hypertrophic cardiomyopathy; or * Significant systemic ventricular outflow obstruction * 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) * Bradycardia: heart rate \< 50 beats per minute (BPM) * Use of an investigational drug or beta adrenergic blockers, including metoprolol, sotalol, within 30 days of enrollment * History of drug sensitivity or allergic reaction to alpha or beta-blockers * Low resting systolic blood pressure: \< 90 mmHg * Use of any other blood pressure lowering medication for treatment of hypertension within 30 days of enrollment except calcium channel blockers and diuretics * History or current clinical evidence of moderate-to-severe obstructive pulmonary disease or reactive airway diseases (i.e. asthma) requiring therapy * Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 3 times upper limit of 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 * Uncontrolled diabetes (controlled diabetes per the American Diabetes Association and International Diabetes Center's Glycemic Target Goals is hemoglobin A1C \< 7%) * Anemia (hematocrit \< 28%) * Currently using select CYP2D6 inhibitor or inducer medications * Inability to swallow pills * Female patients who are pregnant are not eligible; women of childbearing potential require a negative pregnancy test prior to starting study drug * Lactating females are not eligible unless they have agreed to not breastfeed their infants * Sexually active female patients of reproductive potential are not eligible unless they agree to use an effective contraceptive method during study and for 2 months after stopping the study drug; abstinence is an acceptable method of birth control * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
healthy Volunteers: false
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients receive low-dose carvedilol PO QD or BID for 24 months.
intervention Names
Drug: Carvedilol
Other: Laboratory Biomarker Analysis
Other: Pharmacogenomic Study
Other: Pharmacological Study
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
label
Arm I (carvedilol)
type
EXPERIMENTAL
description
Patients receive placebo PO QD or BID for 24 months.
intervention Names
Other: Laboratory Biomarker Analysis
Other: Pharmacogenomic Study
Other: Pharmacological Study
Other: Placebo Administration
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
label
Arm II (placebo)
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Arm I (carvedilol)
description
Given PO
name
Carvedilol
other Names
Coreg
type
DRUG
arm Group Labels
Arm I (carvedilol)
Arm II (placebo)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Arm I (carvedilol)
Arm II (placebo)
description
Correlative studies
name
Pharmacogenomic Study
other Names
PHARMACOGENOMIC
type
OTHER
arm Group Labels
Arm I (carvedilol)
Arm II (placebo)
description
Correlative studies
name
Pharmacological Study
type
OTHER
arm Group Labels
Arm II (placebo)
description
Given PO
name
Placebo Administration
type
OTHER
arm Group Labels
Arm I (carvedilol)
Arm II (placebo)
description
Ancillary studies
name
Quality-of-Life Assessment
other Names
Quality of Life Assessment
type
OTHER
arm Group Labels
Arm I (carvedilol)
Arm II (placebo)
description
Ancillary studies
name
Questionnaire Administration
type
OTHER

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

PREVENTION

Enrollment

count: 196
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Z-score of the ratio of left ventricular (LV) posterior wall dimension of systole to internal LV dimension in diastole, calculated for each subject by subtracting the reference healthy population mean, then dividing by the standard deviation. The Z-score indicates the number of standard deviations away from the mean of the reference population. Negative Z- score indicates worse outcome. The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz)
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation

secondary Outcomes

description
Echocardiographic measure of left ventricular (LV) afterload based on LV pressure (P), volume (V), and wall thickness (T), calculated by the formula (P x V)/T, which equals the number referred to below in the Measure Type. The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Left Ventricular End-systolic Wall Stress
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
Thickness of cardiac muscle (in cm) of the left ventricle at the end of systole. The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Left Ventricular End-systolic Dimension
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
The amount of blood (in ml) in the heart's left ventricle just after the heart contracts. The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Left Ventricular End-systolic Volume
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
Thickness of cardiac muscle (in cm) of the left ventricle at the end of diastole. The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Left Ventricular End-diastolic Dimension
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
The amount of blood (in ml) in the heart's left ventricle just before the heart contracts. The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Left Ventricular End-diastolic Volume
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
The weight of the left ventricle adjusted for body surface area (in g/m2). The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Left Ventricular Mass
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
A measure to assess preload and afterload (in %). The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Fractional Shortening
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
The percentage of blood leaving the heart at the end of diastole. The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Ejection Fraction
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
Ratio of peak velocity blood flow from left ventricular relaxation in early diastole (E wave) to peak velocity flow in late diastole caused by atrial contraction (A wave). "Number" shown for Unit of Measure refers to this ratio. Normal: \>1. Impaired: \<1. The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Peak Early Atrial Divided by Peak Late Atrial Velocities
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
B-type natriuretic peptide- a biomarker for heart failure (in pg/ml). The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average N-terminal Pro B-type Natriuretic Peptide
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
N-terminal pro b-type natriuretic peptide- a biomarker for heart failure (in pg/ml). The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Cardiac N-terminal Pro B-type Natriuretic Peptide
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
description
Troponin I is a biomarker for myocardial cell injury (in ng/ml). The mean is reported by arm at each timepoint with corresponding standard errors.
measure
Average Cardiac Troponin I
time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation

Full study description

brief Summary: This phase IIb trial studies how well low-dose carvedilol works in preventing heart failure in cancer survivors exposed to high dose anthracyclines for management of childhood cancer. Patients who received high-dose anthracycline chemotherapy are at a much greater risk for developing heart failure compared to survivors who didn't get any anthracycline chemotherapy. Heart failure happens when the heart muscle has been weakened and can't pump blood as well as it should. Carvedilol may help lower the risk of cardiovascular complications.
detailed Description: PRIMARY OBJECTIVE: I. To determine the impact of a two-year course of low-dose carvedilol on surrogate echocardiographic indices of heart failure (HF) risk, including: Left ventricular (LV) posterior wall thickness-dimension ratio (LV T-D); LV systolic and diastolic function, and afterload; Natriuretic peptides, troponins, and galectin-3. SECONDARY OBJECTIVES: I. To establish safety and tolerability of this two-year course of low-dose carvedilol, assessing both objective measures (hepatic function) and patient reported outcomes. II. To examine the modifying effect of demographic, clinical, and molecular characteristics on the risk: benefit ratio from this two-year carvedilol intervention. EXPLORATORY OBJECTIVE: I. To evaluate the long-term efficacy of carvedilol in preventing cardiomyopathy and/or heart failure in high-risk childhood cancer survivors. OUTLINE: This is a dose-escalation study. Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive low-dose carvedilol orally (PO) once daily (QD) or twice daily (BID) for 24 months. ARM II: Patients receive placebo PO QD or BID for 24 months. After completion of study treatment, patients are followed up for 3 years.

Source references

references

citation
Armenian SH, Hudson MM, Chen MH, Colan SD, Lindenfeld L, Mills G, Siyahian A, Gelehrter S, Dang H, Hein W, Green DM, Robison LL, Wong FL, Douglas PS, Bhatia S. Rationale and design of the Children's Oncology Group (COG) study ALTE1621: a randomized, placebo-controlled trial to determine if low-dose carvedilol can prevent anthracycline-related left ventricular remodeling in childhood cancer survivors at high risk for developing heart failure. BMC Cardiovasc Disord. 2016 Oct 4;16(1):187. doi: 10.1186/s12872-016-0364-6.
pmid
27716152
type
DERIVED