NCT02717507

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
196

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Apr 2016

Longer than P75 for phase_2

Geographic Reach
4 countries

91 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 9, 2016

Completed
14 days until next milestone

First Posted

Study publicly available on registry

March 23, 2016

Completed
12 days until next milestone

Study Start

First participant enrolled

April 4, 2016

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2022

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

September 29, 2023

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2025

Completed
Last Updated

April 23, 2025

Status Verified

April 1, 2025

Enrollment Period

6.2 years

First QC Date

March 9, 2016

Results QC Date

May 24, 2023

Last Update Submit

April 16, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (19)

  • Average Left Ventricular End-systolic Wall Stress

    Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation

  • Average Left Ventricular End-systolic Dimension

    Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation

  • Average Left Ventricular End-systolic Volume

    Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation

  • Average Left Ventricular End-diastolic Dimension

    Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation

  • Average Left Ventricular End-diastolic Volume

    Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation

  • +14 more secondary outcomes

Study Arms (2)

Arm I (carvedilol)

EXPERIMENTAL

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

Drug: CarvedilolOther: Laboratory Biomarker AnalysisOther: Pharmacogenomic StudyOther: Pharmacological StudyOther: Quality-of-Life AssessmentOther: Questionnaire Administration

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo PO QD or BID for 24 months.

Other: Laboratory Biomarker AnalysisOther: Pharmacogenomic StudyOther: Pharmacological StudyOther: Placebo AdministrationOther: Quality-of-Life AssessmentOther: Questionnaire Administration

Interventions

Given PO

Also known as: Coreg
Arm I (carvedilol)

Correlative studies

Arm I (carvedilol)Arm II (placebo)

Correlative studies

Also known as: PHARMACOGENOMIC
Arm I (carvedilol)Arm II (placebo)

Correlative studies

Arm I (carvedilol)Arm II (placebo)

Given PO

Arm II (placebo)

Ancillary studies

Also known as: Quality of Life Assessment
Arm I (carvedilol)Arm II (placebo)

Ancillary studies

Arm I (carvedilol)Arm II (placebo)

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (91)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

Location

Kaiser Permanente Downey Medical Center

Downey, California, 90242, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

Location

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, 80218, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

Location

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Nemours Children's Hospital

Orlando, Florida, 32827, United States

Location

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32504, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, 33607, United States

Location

Saint Mary's Medical Center

West Palm Beach, Florida, 33407, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, 60453, United States

Location

Advocate Children's Hospital-Park Ridge

Park Ridge, Illinois, 60068, United States

Location

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States

Location

Blank Children's Hospital

Des Moines, Iowa, 50309, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Children's Hospital New Orleans

New Orleans, Louisiana, 70118, United States

Location

Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

Location

Sunrise Hospital and Medical Center

Las Vegas, Nevada, 89109, United States

Location

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, 89135, United States

Location

Summerlin Hospital Medical Center

Las Vegas, Nevada, 89144, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Saint Joseph's Regional Medical Center

Paterson, New Jersey, 07503, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

Location

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, 11040, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Mission Hospital

Asheville, North Carolina, 28801, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Emanuel Children's Hospital

Portland, Oregon, 97227, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

El Paso Children's Hospital

El Paso, Texas, 79905, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

Location

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, 98405, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6008, Australia

Location

Perth Children's Hospital

Perth, Western Australia, 6009, Australia

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Starship Children's Hospital

Grafton, Auckland, 1145, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

CarvedilolPharmacogenomic Testing

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

PropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesCarbazolesIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHeterocyclic Compounds, 3-RingGenetic TestingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative TechniquesGenetic TechniquesGenetic ServicesHealth ServicesHealth Care Facilities Workforce and ServicesDiagnostic ServicesPreventive Health Services

Results Point of Contact

Title
Results Reporting Coordinator
Organization
Children's Oncology Group

Study Officials

  • Saro H Armenian

    Children's Oncology Group

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 9, 2016

First Posted

March 23, 2016

Study Start

April 4, 2016

Primary Completion

June 30, 2022

Study Completion

March 31, 2025

Last Updated

April 23, 2025

Results First Posted

September 29, 2023

Record last verified: 2025-04

Locations