| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2016-00232 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| ALTE1621 | Other Identifier | Children's Oncology Group | |
| COG-ALTE1621 | Other Identifier | DCP | |
| ALTE1621 | Other Identifier | CTEP | |
| R01CA196854 | U.S. NIH Grant/Contract | View source | |
| UG1CA189955 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I (carvedilol) | Experimental | Patients receive low-dose carvedilol PO QD or BID for 24 months. |
|
| Arm II (placebo) | Placebo Comparator | Patients receive placebo PO QD or BID for 24 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carvedilol | Drug | Given PO |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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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
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)
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)
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
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| Name | Affiliation | Role |
|---|---|---|
| Saro H Armenian | Children's Oncology Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Alabama | Birmingham | Alabama | 35233 | United States | ||
| Phoenix Childrens Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27716152 | Derived | 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. |
| Label | URL |
|---|---|
| Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Congestive Heart Failure (PREVENT-CHF): A Phase IIB Randomized Placebo-Controlled Trial | View source |
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196 pts were enrolled (109 pts enrolled with Childrens Oncology Group (COG) and 87 pts enrolled on a pilot study at City of Hope (COH) 182 of those pts started tx (14 excluded: 6 ineligible and 8 pts started tx). (The (109) enrollment number in the protocol section reflects the number of pts enrolled on the COG portion of the study. Per Section 9.2 of the protocol (pt accrual and expected duration of the trial), 87 pts had already been accrued through a different mechanism the pilot study)
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm I (Carvedilol) | Patients receive low-dose carvedilol orally (PO) once daily (QD) or twice daily (BID) for 24 months. |
| FG001 | Arm II (Placebo) | Patients receive placebo PO QD or BID for 24 months. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 8, 2020 |
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| Laboratory Biomarker Analysis |
| Other |
Correlative studies |
|
| Pharmacogenomic Study | Other | Correlative studies |
|
|
| Pharmacological Study | Other | Correlative studies |
|
| Placebo Administration | Other | Given PO |
|
| Quality-of-Life Assessment | Other | Ancillary studies |
|
|
| Questionnaire Administration | Other | Ancillary studies |
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Responses at days 14 to 730 were combined |
| Phoenix |
| Arizona |
| 85016 |
| United States |
| Arkansas Children's Hospital | Little Rock | Arkansas | 72202-3591 | United States |
| Kaiser Permanente Downey Medical Center | Downey | California | 90242 | United States |
| City of Hope Comprehensive Cancer Center | Duarte | California | 91010 | United States |
| Miller Children's and Women's Hospital Long Beach | Long Beach | California | 90806 | United States |
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States |
| Kaiser Permanente-Oakland | Oakland | California | 94611 | United States |
| Children's Hospital of Orange County | Orange | California | 92868 | United States |
| University of California Davis Comprehensive Cancer Center | Sacramento | California | 95817 | United States |
| Rady Children's Hospital - San Diego | San Diego | California | 92123 | United States |
| Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | Torrance | California | 90502 | United States |
| Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
| Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado | 80218 | United States |
| Yale University | New Haven | Connecticut | 06520 | United States |
| Alfred I duPont Hospital for Children | Wilmington | Delaware | 19803 | United States |
| MedStar Georgetown University Hospital | Washington D.C. | District of Columbia | 20007 | United States |
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010 | United States |
| Golisano Children's Hospital of Southwest Florida | Fort Myers | Florida | 33908 | United States |
| University of Florida Health Science Center - Gainesville | Gainesville | Florida | 32610 | United States |
| Nemours Children's Clinic-Jacksonville | Jacksonville | Florida | 32207 | United States |
| AdventHealth Orlando | Orlando | Florida | 32803 | United States |
| Nemours Children's Hospital | Orlando | Florida | 32827 | United States |
| Nemours Children's Clinic - Pensacola | Pensacola | Florida | 32504 | United States |
| Johns Hopkins All Children's Hospital | St. Petersburg | Florida | 33701 | United States |
| Tampa General Hospital | Tampa | Florida | 33606 | United States |
| Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa | Florida | 33607 | United States |
| Saint Mary's Medical Center | West Palm Beach | Florida | 33407 | United States |
| Children's Healthcare of Atlanta - Arthur M Blank Hospital | Atlanta | Georgia | 30329 | United States |
| Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | 96826 | United States |
| Lurie Children's Hospital-Chicago | Chicago | Illinois | 60611 | United States |
| University of Illinois | Chicago | Illinois | 60612 | United States |
| University of Chicago Comprehensive Cancer Center | Chicago | Illinois | 60637 | United States |
| Advocate Children's Hospital-Oak Lawn | Oak Lawn | Illinois | 60453 | United States |
| Advocate Children's Hospital-Park Ridge | Park Ridge | Illinois | 60068 | United States |
| Ascension Saint Vincent Indianapolis Hospital | Indianapolis | Indiana | 46260 | United States |
| Blank Children's Hospital | Des Moines | Iowa | 50309 | United States |
| University of Iowa/Holden Comprehensive Cancer Center | Iowa City | Iowa | 52242 | United States |
| Norton Children's Hospital | Louisville | Kentucky | 40202 | United States |
| Children's Hospital New Orleans | New Orleans | Louisiana | 70118 | United States |
| Ochsner Medical Center Jefferson | New Orleans | Louisiana | 70121 | United States |
| Sinai Hospital of Baltimore | Baltimore | Maryland | 21215 | United States |
| C S Mott Children's Hospital | Ann Arbor | Michigan | 48109 | United States |
| Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | 55404 | United States |
| University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota | 55455 | United States |
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216 | United States |
| Children's Mercy Hospitals and Clinics | Kansas City | Missouri | 64108 | United States |
| Cardinal Glennon Children's Medical Center | St Louis | Missouri | 63104 | United States |
| Children's Hospital and Medical Center of Omaha | Omaha | Nebraska | 68114 | United States |
| University of Nebraska Medical Center | Omaha | Nebraska | 68198 | United States |
| University Medical Center of Southern Nevada | Las Vegas | Nevada | 89102 | United States |
| Sunrise Hospital and Medical Center | Las Vegas | Nevada | 89109 | United States |
| Alliance for Childhood Diseases/Cure 4 the Kids Foundation | Las Vegas | Nevada | 89135 | United States |
| Summerlin Hospital Medical Center | Las Vegas | Nevada | 89144 | United States |
| Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| Saint Joseph's Regional Medical Center | Paterson | New Jersey | 07503 | United States |
| Roswell Park Cancer Institute | Buffalo | New York | 14263 | United States |
| NYU Langone Hospital - Long Island | Mineola | New York | 11501 | United States |
| The Steven and Alexandra Cohen Children's Medical Center of New York | New Hyde Park | New York | 11040 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| Stony Brook University Medical Center | Stony Brook | New York | 11794 | United States |
| Mission Hospital | Asheville | North Carolina | 28801 | United States |
| Children's Hospital Medical Center of Akron | Akron | Ohio | 44308 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| Legacy Emanuel Children's Hospital | Portland | Oregon | 97227 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | 15224 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| BI-LO Charities Children's Cancer Center | Greenville | South Carolina | 29605 | United States |
| Saint Jude Children's Research Hospital | Memphis | Tennessee | 38105 | United States |
| Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | 37232 | United States |
| Dell Children's Medical Center of Central Texas | Austin | Texas | 78723 | United States |
| UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | 75390 | United States |
| El Paso Children's Hospital | El Paso | Texas | 79905 | United States |
| Cook Children's Medical Center | Fort Worth | Texas | 76104 | United States |
| Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | 77030 | United States |
| Methodist Children's Hospital of South Texas | San Antonio | Texas | 78229 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| University of Virginia Cancer Center | Charlottesville | Virginia | 22908 | United States |
| Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia | 23298 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington | 99204 | United States |
| Mary Bridge Children's Hospital and Health Center | Tacoma | Washington | 98405 | United States |
| Princess Margaret Hospital for Children | Perth | Western Australia | 6008 | Australia |
| Perth Children's Hospital | Perth | Western Australia | 6009 | Australia |
| IWK Health Centre | Halifax | Nova Scotia | B3K 6R8 | Canada |
| Starship Children's Hospital | Grafton | Auckland | 1145 | New Zealand |
| Christchurch Hospital | Christchurch | 8011 | New Zealand |
| 2nd Timepoint Assessment of Echocardiology Required to be Analyzable | 31 participants who did not have a second timepoint assessment of echocardiography were excluded, resulting in 151 analyzable participants. |
|
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm I (Carvedilol) | Patients receive low-dose carvedilol orally (PO) once daily (QD) or twice daily (BID) for 24 months. |
| BG001 | Arm II (Placebo) | Patients receive placebo PO QD or BID for 24 months. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | z-score | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | g/cm^2 | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | centimeter | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | ml | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | cm | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | ml | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | g/m^2 | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | Average Fractional Shortening | A measure to assess preload and afterload (in %). The mean is reported by arm at each timepoint with corresponding standard errors. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | percent | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | Percent | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | ratio | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | pg/mL | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | pg/mL | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | ng/mL | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | ng/mL | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Number | 95% Confidence Interval | Proportion of patients with AE | From baseline to month 24 since baseline |
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| Secondary | Average Bilirubin | A liver function measurement (in mg/dL). The mean is reported by arm at each timepoint with corresponding standard errors. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | mg/dL | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | IU/L | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Mean | Standard Error | IU/L | Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Number | 95% Confidence Interval | proportion of participants | Average adherence across 6 months, 12 months, 18 months, 24 months after treatment initiation are calculated. |
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| Secondary | 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. | We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants. | Posted | Number | 95% Confidence Interval | Proportion of patients | Responses at days 14 to 730 were combined |
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Up to 24 months after first dose of drug
Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm I (Carvedilol) | Patients receive low-dose carvedilol orally (PO) once daily (QD) or twice daily (BID) for 24 months. | 0 | 89 | 0 | 89 | 2 | 89 |
| EG001 | Arm II (Placebo) | Patients receive placebo PO QD or BID for 24 months. | 0 | 93 | 0 | 93 | 0 | 93 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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Must obtain prior Sponsor approval
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Results Reporting Coordinator | Children's Oncology Group | 16264470064 | resultsreportingcoordinator@childrensoncologygroup.org |
| May 16, 2023 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077261 | Carvedilol |
| D000071185 | Pharmacogenomic Testing |
| ID | Term |
|---|---|
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D005820 | Genetic Testing |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |
Not provided
Not provided
| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| 12m |
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| 18m |
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| 24m |
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| Other |
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