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Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors

Primary Purpose

Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Carvedilol
Laboratory Biomarker Analysis
Pharmacogenomic Study
Pharmacological Study
Placebo Administration
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hematopoietic and Lymphoid Cell Neoplasm

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital of Alabama
  • Phoenix Childrens Hospital
  • Arkansas Children's Hospital
  • Kaiser Permanente Downey Medical Center
  • City of Hope Comprehensive Cancer Center
  • Miller Children's and Women's Hospital Long Beach
  • Children's Hospital Los Angeles
  • Kaiser Permanente-Oakland
  • Children's Hospital of Orange County
  • University of California Davis Comprehensive Cancer Center
  • Rady Children's Hospital - San Diego
  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • Children's Hospital Colorado
  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
  • Yale University
  • Alfred I duPont Hospital for Children
  • MedStar Georgetown University Hospital
  • Children's National Medical Center
  • Golisano Children's Hospital of Southwest Florida
  • University of Florida Health Science Center - Gainesville
  • Nemours Children's Clinic-Jacksonville
  • AdventHealth Orlando
  • Nemours Children's Hospital
  • Nemours Children's Clinic - Pensacola
  • Johns Hopkins All Children's Hospital
  • Tampa General Hospital
  • Saint Joseph's Hospital/Children's Hospital-Tampa
  • Saint Mary's Hospital
  • Children's Healthcare of Atlanta - Egleston
  • Kapiolani Medical Center for Women and Children
  • Lurie Children's Hospital-Chicago
  • University of Illinois
  • University of Chicago Comprehensive Cancer Center
  • Advocate Children's Hospital-Oak Lawn
  • Advocate Children's Hospital-Park Ridge
  • Ascension Saint Vincent Indianapolis Hospital
  • Blank Children's Hospital
  • University of Iowa/Holden Comprehensive Cancer Center
  • Norton Children's Hospital
  • Children's Hospital New Orleans
  • Ochsner Medical Center Jefferson
  • Sinai Hospital of Baltimore
  • C S Mott Children's Hospital
  • Children's Hospitals and Clinics of Minnesota - Minneapolis
  • University of Minnesota/Masonic Cancer Center
  • Mayo Clinic in Rochester
  • University of Mississippi Medical Center
  • Children's Mercy Hospitals and Clinics
  • Cardinal Glennon Children's Medical Center
  • Children's Hospital and Medical Center of Omaha
  • University of Nebraska Medical Center
  • University Medical Center of Southern Nevada
  • Sunrise Hospital and Medical Center
  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
  • Summerlin Hospital Medical Center
  • Hackensack University Medical Center
  • Saint Joseph's Regional Medical Center
  • Roswell Park Cancer Institute
  • NYU Winthrop Hospital
  • The Steven and Alexandra Cohen Children's Medical Center of New York
  • Memorial Sloan Kettering Cancer Center
  • University of Rochester
  • Stony Brook University Medical Center
  • Mission Hospital
  • Children's Hospital Medical Center of Akron
  • Cincinnati Children's Hospital Medical Center
  • University of Oklahoma Health Sciences Center
  • Legacy Emanuel Children's Hospital
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh of UPMC
  • Medical University of South Carolina
  • BI-LO Charities Children's Cancer Center
  • Saint Jude Children's Research Hospital
  • Vanderbilt University/Ingram Cancer Center
  • Dell Children's Medical Center of Central Texas
  • UT Southwestern/Simmons Cancer Center-Dallas
  • El Paso Children's Hospital
  • Cook Children's Medical Center
  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
  • Methodist Children's Hospital of South Texas
  • University of Texas Health Science Center at San Antonio
  • University of Virginia Cancer Center
  • Virginia Commonwealth University/Massey Cancer Center
  • Seattle Children's Hospital
  • Providence Sacred Heart Medical Center and Children's Hospital
  • Mary Bridge Children's Hospital and Health Center
  • Princess Margaret Hospital for Children
  • Perth Children's Hospital
  • IWK Health Centre
  • Starship Children's Hospital
  • Christchurch Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (carvedilol)

Arm II (placebo)

Arm Description

Patients receive low-dose carvedilol PO QD or BID for 24 months.

Patients receive placebo PO QD or BID for 24 months.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Average Left Ventricular End-systolic Wall Stress
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.
Average Left Ventricular End-systolic Volume
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.
Average Left Ventricular End-diastolic Dimension
Thickness of cardiac muscle (in ml) of the left ventricle at the end of diastole. The mean is reported by arm at each timepoint with corresponding standard errors.
Average Left Ventricular End-diastolic Dimension
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.
Average Left Ventricular Mass
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.
Average Fractional Shortening
A measure to assess preload and afterload (in %). The mean is reported by arm at each timepoint with corresponding standard errors.
Average Ejection Fraction
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.
Average Peak Early Atrial Divided by Peak Late Atrial Velocities
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.
Average N-terminal Pro B-type Natriuretic Peptide
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.
Average Cardiac N-terminal Pro B-type Natriuretic Peptide
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.
Average Cardiac Troponin I
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.
Average Galectin-3
A protein produced by activated macrophages, and a member of a family of β-galactoside-binding lectings and promotes cardiac fibroblast proliferation and collagen synthesis following myocadial injury (in ng/ml). The mean is reported by arm at each timepoint with corresponding standard errors.
Proportion of Patients With Reportable Adverse Events as Described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).
Patients with toxicities reported via CTEP-AERS and all Grade ≥ 2 adverse events (AEs) that can be attributed probably or definitely to the study drug are considered to have AEs. The proportion of patients with AEs are reported by arm with corresponding 95% confidence intervals.
Average Bilirubin
A liver function measurement (in mg/dL). The mean is reported by arm at each timepoint with corresponding standard errors.
Average Aspartate Aminotransferase
A liver function measurement (in U/L). Normal range is 14-20 for men, 10-36 for women. The mean is reported by arm at each timepoint with corresponding standard errors.
Average Alanine Aminotransferase
A liver function measurement (in U/L). Normal range is 8-48 IU/L. The mean is reported by arm at each timepoint with corresponding standard errors.
Proportion of Participants With Average Adherence > 90%
The number of pills taken out of the total prescribed in a 3-month period, averaged across all study time points. The proportion of participants with average adherence rate >90% is computed by arm and corresponding 95% confidence intervals are reported.
Proportion of Patients Who Responded "Moderately", "Quite a Bit", or "Extremely" to How Bothersome the Symptom of DIARRHEA Was at Any Post-day 0 Assessment Time Point.
In a questionnaire, patients responded Yes/No to certain symptoms. If answered Yes, they selected "slightly", "moderately", "quite a bit", or "extremely" regarding how bothersome the symptom was. The proportion of participants responding with any of these three categories was calculated by arm, and corresponding 95% confidence intervals are reported.

Full Information

First Posted
March 9, 2016
Last Updated
October 17, 2023
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02717507
Brief Title
Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors
Official Title
Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Heart Failure (PREVENT-HF): A Phase 2b Randomized Placebo-Controlled (Carvedilol) Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 4, 2016 (Actual)
Primary Completion Date
June 30, 2022 (Actual)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
196 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (carvedilol)
Arm Type
Experimental
Arm Description
Patients receive low-dose carvedilol PO QD or BID for 24 months.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo PO QD or BID for 24 months.
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Other Intervention Name(s)
Coreg
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Pharmacogenomic Study
Other Intervention Name(s)
PHARMACOGENOMIC
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Placebo Administration
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz)
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.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary Outcome Measure Information:
Title
Average Left Ventricular End-systolic Wall Stress
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.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Left Ventricular End-systolic Volume
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.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Left Ventricular End-diastolic Dimension
Description
Thickness of cardiac muscle (in ml) of the left ventricle at the end of diastole. The mean is reported by arm at each timepoint with corresponding standard errors.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Left Ventricular End-diastolic Dimension
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.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Left Ventricular Mass
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.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Fractional Shortening
Description
A measure to assess preload and afterload (in %). The mean is reported by arm at each timepoint with corresponding standard errors.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Ejection Fraction
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.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Peak Early Atrial Divided by Peak Late Atrial Velocities
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.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average N-terminal Pro B-type Natriuretic Peptide
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.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Cardiac N-terminal Pro B-type Natriuretic Peptide
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.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Cardiac Troponin I
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.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Galectin-3
Description
A protein produced by activated macrophages, and a member of a family of β-galactoside-binding lectings and promotes cardiac fibroblast proliferation and collagen synthesis following myocadial injury (in ng/ml). The mean is reported by arm at each timepoint with corresponding standard errors.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Proportion of Patients With Reportable Adverse Events as Described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).
Description
Patients with toxicities reported via CTEP-AERS and all Grade ≥ 2 adverse events (AEs) that can be attributed probably or definitely to the study drug are considered to have AEs. The proportion of patients with AEs are reported by arm with corresponding 95% confidence intervals.
Time Frame
From baseline to month 24 since baseline
Title
Average Bilirubin
Description
A liver function measurement (in mg/dL). The mean is reported by arm at each timepoint with corresponding standard errors.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Aspartate Aminotransferase
Description
A liver function measurement (in U/L). Normal range is 14-20 for men, 10-36 for women. The mean is reported by arm at each timepoint with corresponding standard errors.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Average Alanine Aminotransferase
Description
A liver function measurement (in U/L). Normal range is 8-48 IU/L. The mean is reported by arm at each timepoint with corresponding standard errors.
Time Frame
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Title
Proportion of Participants With Average Adherence > 90%
Description
The number of pills taken out of the total prescribed in a 3-month period, averaged across all study time points. The proportion of participants with average adherence rate >90% is computed by arm and corresponding 95% confidence intervals are reported.
Time Frame
Average adherence across 6 months, 12 months, 18 months, 24 months after treatment initiation are calculated.
Title
Proportion of Patients Who Responded "Moderately", "Quite a Bit", or "Extremely" to How Bothersome the Symptom of DIARRHEA Was at Any Post-day 0 Assessment Time Point.
Description
In a questionnaire, patients responded Yes/No to certain symptoms. If answered Yes, they selected "slightly", "moderately", "quite a bit", or "extremely" regarding how bothersome the symptom was. The proportion of participants responding with any of these three categories was calculated by arm, and corresponding 95% confidence intervals are reported.
Time Frame
responses at days 14 to 730 were combined

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saro H Armenian
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Phoenix Childrens Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202-3591
Country
United States
Facility Name
Kaiser Permanente Downey Medical Center
City
Downey
State/Province
California
ZIP/Postal Code
90242
Country
United States
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Miller Children's and Women's Hospital Long Beach
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Kaiser Permanente-Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Rady Children's Hospital - San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Alfred I duPont Hospital for Children
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
MedStar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Golisano Children's Hospital of Southwest Florida
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33908
Country
United States
Facility Name
University of Florida Health Science Center - Gainesville
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Nemours Children's Clinic-Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
AdventHealth Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Nemours Children's Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Nemours Children's Clinic - Pensacola
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
Johns Hopkins All Children's Hospital
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Tampa General Hospital
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Saint Joseph's Hospital/Children's Hospital-Tampa
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Saint Mary's Hospital
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Children's Healthcare of Atlanta - Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Kapiolani Medical Center for Women and Children
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96826
Country
United States
Facility Name
Lurie Children's Hospital-Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Illinois
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Advocate Children's Hospital-Oak Lawn
City
Oak Lawn
State/Province
Illinois
ZIP/Postal Code
60453
Country
United States
Facility Name
Advocate Children's Hospital-Park Ridge
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
Facility Name
Ascension Saint Vincent Indianapolis Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Blank Children's Hospital
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309
Country
United States
Facility Name
University of Iowa/Holden Comprehensive Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Norton Children's Hospital
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Children's Hospital New Orleans
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70118
Country
United States
Facility Name
Ochsner Medical Center Jefferson
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Sinai Hospital of Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
C S Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota - Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
University of Minnesota/Masonic Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Children's Mercy Hospitals and Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Cardinal Glennon Children's Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Children's Hospital and Medical Center of Omaha
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
University Medical Center of Southern Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89102
Country
United States
Facility Name
Sunrise Hospital and Medical Center
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
Facility Name
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89135
Country
United States
Facility Name
Summerlin Hospital Medical Center
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89144
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Saint Joseph's Regional Medical Center
City
Paterson
State/Province
New Jersey
ZIP/Postal Code
07503
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
NYU Winthrop Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
The Steven and Alexandra Cohen Children's Medical Center of New York
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Stony Brook University Medical Center
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Mission Hospital
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Children's Hospital Medical Center of Akron
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Legacy Emanuel Children's Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
BI-LO Charities Children's Cancer Center
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Saint Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Dell Children's Medical Center of Central Texas
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Facility Name
UT Southwestern/Simmons Cancer Center-Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
El Paso Children's Hospital
City
El Paso
State/Province
Texas
ZIP/Postal Code
79905
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Methodist Children's Hospital of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Virginia Cancer Center
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Providence Sacred Heart Medical Center and Children's Hospital
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Mary Bridge Children's Hospital and Health Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Princess Margaret Hospital for Children
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Facility Name
Perth Children's Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
IWK Health Centre
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3K 6R8
Country
Canada
Facility Name
Starship Children's Hospital
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1145
Country
New Zealand
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand

12. IPD Sharing Statement

Citations:
PubMed Identifier
27716152
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.
Results Reference
derived
Links:
URL
https://clinicaltrials.gov/ct2/show/NCT01347970?term=NCT01347970&draw=2&rank=1
Description
Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Congestive Heart Failure (PREVENT-CHF): A Phase IIB Randomized Placebo-Controlled Tria

Learn more about this trial

Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors

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