Hematopoietic and Lymphoid Cell NeoplasmPhase 2NCT02717507
Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors
A Phase 2 study testing Carvedilol, Laboratory Biomarker Analysis and Pharmacogenomic Study in people with Hematopoietic and Lymphoid Cell Neoplasm and Malignant Solid Neoplasm, run by Children's Oncology Group at 91 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
- What is being tested?
- Carvedilol, Laboratory Biomarker Analysis and Pharmacogenomic Study
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 196 participants
- Where
- 91 sitesin 4 countries
- Study dates
- 4 Apr 2016to 31 Mar 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 27Show fewer
- 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
Trial locations and contacts
91 sites in 4 countries.
91 sites in 4 countries
United States86 sites
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Mission Hospital
Asheville, North Carolina, 28801
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Roswell Park Cancer Institute
Buffalo, New York, 14263
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Blank Children's Hospital
Des Moines, Iowa, 50309
Kaiser Permanente Downey Medical Center
Downey, California, 90242
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
El Paso Children's Hospital
El Paso, Texas, 79905
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Cook Children's Medical Center
Fort Worth, Texas, 76104
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Norton Children's Hospital
Louisville, Kentucky, 40202
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Yale University
New Haven, Connecticut, 06520
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Orange County
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Nemours Children's Hospital
Orlando, Florida, 32827
Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois, 60068
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
Seattle Children's Hospital
Seattle, Washington, 98105
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Stony Brook University Medical Center
Stony Brook, New York, 11794
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Tampa General Hospital
Tampa, Florida, 33606
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Saint Mary's Medical Center
West Palm Beach, Florida, 33407
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Australia2 sites
Princess Margaret Hospital for Children
Perth, Western Australia, 6008
Perth Children's Hospital
Perth, Western Australia, 6009
New Zealand2 sites
Christchurch Hospital
Christchurch, 8011
Starship Children's Hospital
Grafton, Auckland, 1145
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- Being tested
- Carvedilol, Laboratory Biomarker Analysis, Pharmacogenomic Study, Pharmacological Study, Placebo Administration
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Also called Coreg
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Pharmacogenomic StudyOther
Also called PHARMACOGENOMIC
Correlative studies
Correlative studies
Placebo AdministrationOther
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (carvedilol) | Experimental | Patients receive low-dose carvedilol PO QD or BID for 24 months. Receives: Drug: Carvedilol; Other: Laboratory Biomarker Analysis; Other: Pharmacogenomic Study; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Arm II (placebo) | Placebo comparator | Patients receive placebo PO QD or BID for 24 months. Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacogenomic Study; Other: Pharmacological Study; Other: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcomes (19)
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Left Ventricular End-systolic Dimension
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Left Ventricular End-diastolic Dimension
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Left Ventricular End-diastolic Volume
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Fractional Shortening
A measure to assess preload and afterload (in %). The mean is reported by arm at each timepoint with corresponding standard errors.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: From baseline to month 24 since baseline
Average Bilirubin
A liver function measurement (in mg/dL). The mean is reported by arm at each timepoint with corresponding standard errors.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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.
Measured: Average adherence across 6 months, 12 months, 18 months, 24 months after treatment initiation are calculated.
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.
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.
Measured: Responses at days 14 to 730 were combined
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2016 (estimated)
- Study start4 Apr 2016
- Primary completion30 Jun 2022
- Study completion31 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematopoietic and Lymphoid Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Saro H Armenian, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02717507
- Sponsor's protocol ID
- ALTE1621
- Other IDs
- NCI-2016-00232, ALTE1621, COG-ALTE1621, ALTE1621, R01CA196854, UG1CA189955
- Status last verified
- Apr 2025
- First submitted
- 9 Mar 2016
- Last updated
- 23 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 27716152
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02717507
- Acronym / sponsor ID
- ALTE1621
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 196 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 4 Apr 2016 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 31 Mar 2025 (actual)
- First posted
- 23 Mar 2016 (estimated)
- Results
- Posted 29 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (carvedilol) | Experimental | Drug: Carvedilol, Other: Laboratory Biomarker Analysis, Other: Pharmacogenomic Study, Other: Pharmacological Study, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients receive low-dose carvedilol PO QD or BID for 24 months. |
| Arm II (placebo) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: Pharmacogenomic Study, Other: Pharmacological Study, Other: Placebo Administration, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients receive placebo PO QD or BID for 24 months. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
- Patient must have completed cancer treatment >= 2 years prior to study enrollment
Key exclusion criteria (27 listed)
- Receiving treatment for cardiomyopathy or heart failure
- Ejection fraction of < 50% (by radionuclide angiogram or echocardiogram) or shortening fraction of < 25% (by echocardiogram)
- Uncorrected primary obstructive or severe regurgitative valvular disease:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarvedilolAlso: CoregGiven PO | Drug | Arm I (carvedilol) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (carvedilol), Arm II (placebo) |
| Pharmacogenomic StudyAlso: PHARMACOGENOMICCorrelative studies | Other | Arm I (carvedilol), Arm II (placebo) |
| Pharmacological StudyCorrelative studies | Other | Arm I (carvedilol), Arm II (placebo) |
| Placebo AdministrationGiven PO | Other | Arm II (placebo) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Arm I (carvedilol), Arm II (placebo) |
| Questionnaire AdministrationAncillary studies | Other | Arm I (carvedilol), Arm II (placebo) |
Primary outcome
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
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.
19 secondary outcomes
Average Left Ventricular End-systolic Wall Stress
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Left Ventricular End-systolic Dimension
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Left Ventricular End-systolic Volume
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Left Ventricular End-diastolic Dimension
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Left Ventricular End-diastolic Volume
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Left Ventricular Mass
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Fractional Shortening
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Ejection Fraction
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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
Average N-terminal Pro B-type Natriuretic Peptide
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
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
Average Cardiac Troponin I
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Galectin-3
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Proportion of Patients With Reportable Adverse Events as Described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).
Time frame: From baseline to month 24 since baseline
Average Bilirubin
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Aspartate Aminotransferase
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Average Alanine Aminotransferase
Time frame: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Proportion of Participants With Average Adherence > 90%
Time frame: Average adherence across 6 months, 12 months, 18 months, 24 months after treatment initiation are calculated.
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.
Time frame: Responses at days 14 to 730 were combined
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27716152Armenian 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.
- Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Congestive Heart Failure (PREVENT-CHF): A Phase IIB Randomized Placebo-Controlled TrialLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Saro H Armenian principal investigator
Children's Oncology Group
91 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carvedilol, Laboratory Biomarker Analysis and Pharmacogenomic Study in people with Hematopoietic and Lymphoid Cell Neoplasm and Malignant Solid Neoplasm, run by Children's Oncology Group at 91 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 91 sites in United States, Australia, New Zealand, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02717507, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2025; AzTrials last refreshed its copy on 8 Nov 2026.