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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02717507




Registration number
NCT02717507
Ethics application status
Date submitted
9/03/2016
Date registered
23/03/2016
Date last updated
9/04/2024

Titles & IDs
Public title
Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors
Scientific 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
Secondary ID [1] 0 0
NCI-2016-00232
Secondary ID [2] 0 0
ALTE1621
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hematopoietic and Lymphoid Cell Neoplasm 0 0
Malignant Solid Neoplasm 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Carvedilol
Other interventions - Laboratory Biomarker Analysis
Other interventions - Pharmacogenomic Study
Other interventions - Pharmacological Study
Other interventions - Placebo Administration
Other interventions - Quality-of-Life Assessment
Other interventions - Questionnaire Administration

Experimental: Arm I (carvedilol) - Patients receive low-dose carvedilol PO QD or BID for 24 months.

Placebo comparator: Arm II (placebo) - Patients receive placebo PO QD or BID for 24 months.


Treatment: Drugs: Carvedilol
Given PO

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Other interventions: Pharmacogenomic Study
Correlative studies

Other interventions: Pharmacological Study
Correlative studies

Other interventions: Placebo Administration
Given PO

Other interventions: Quality-of-Life Assessment
Ancillary studies

Other interventions: Questionnaire Administration
Ancillary studies
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz)
Timepoint [1] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [1] 0 0
Average Left Ventricular End-systolic Wall Stress
Timepoint [1] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [2] 0 0
Average Left Ventricular End-systolic Dimension
Timepoint [2] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [3] 0 0
Average Left Ventricular End-systolic Volume
Timepoint [3] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [4] 0 0
Average Left Ventricular End-diastolic Dimension
Timepoint [4] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [5] 0 0
Average Left Ventricular End-diastolic Volume
Timepoint [5] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [6] 0 0
Average Left Ventricular Mass
Timepoint [6] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [7] 0 0
Average Fractional Shortening
Timepoint [7] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [8] 0 0
Average Ejection Fraction
Timepoint [8] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [9] 0 0
Average Peak Early Atrial Divided by Peak Late Atrial Velocities
Timepoint [9] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [10] 0 0
Average N-terminal Pro B-type Natriuretic Peptide
Timepoint [10] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [11] 0 0
Average Cardiac N-terminal Pro B-type Natriuretic Peptide
Timepoint [11] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [12] 0 0
Average Cardiac Troponin I
Timepoint [12] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [13] 0 0
Average Galectin-3
Timepoint [13] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [14] 0 0
Proportion of Patients With Reportable Adverse Events as Described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).
Timepoint [14] 0 0
From baseline to month 24 since baseline
Secondary outcome [15] 0 0
Average Bilirubin
Timepoint [15] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [16] 0 0
Average Aspartate Aminotransferase
Timepoint [16] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [17] 0 0
Average Alanine Aminotransferase
Timepoint [17] 0 0
Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
Secondary outcome [18] 0 0
Proportion of Participants With Average Adherence > 90%
Timepoint [18] 0 0
Average adherence across 6 months, 12 months, 18 months, 24 months after treatment initiation are calculated.
Secondary outcome [19] 0 0
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.
Timepoint [19] 0 0
Responses at days 14 to 730 were combined

Eligibility
Key inclusion criteria
* Males and females must weigh >= 40 Kg
* Patient must have had a cancer diagnosis < 22 years of age, irrespective of current age
* Patient must have a lifetime cumulative anthracycline dose of >= 250 mg/m^2 DOXOrubicin equivalent without the protection of dexrazoxane (Zinecard) therapy; the anthracycline dose threshold must be met as part of the treatment of a cancer that was diagnosed at < 22 years of age

* Note: Institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) can be used to document lifetime receipt of anthracycline dose
* Patient must have completed cancer treatment >= 2 years prior to study enrollment
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Receiving treatment for cardiomyopathy or heart failure
* Ejection fraction of < 50% (by radionuclide angiogram or echocardiogram) or shortening fraction of < 25% (by echocardiogram)

* Note: for instances where both are reported, and one is below the threshold, the site will have the option to re-measure it centrally at the core lab
* Uncorrected primary obstructive or severe regurgitative valvular disease:

* Nondilated (restrictive); or
* Hypertrophic cardiomyopathy; or
* Significant systemic ventricular outflow obstruction
* Sustained or symptomatic ventricular dysrhythmias uncontrolled with drug therapy or implantable device
* Significant conduction defects (i.e. second or third degree atrio-ventricular block or sick sinus syndrome)
* Bradycardia: heart rate < 50 beats per minute (BPM)
* Use of an investigational drug or beta adrenergic blockers, including metoprolol, sotalol, within 30 days of enrollment
* History of drug sensitivity or allergic reaction to alpha or beta-blockers
* Low resting systolic blood pressure: < 90 mmHg
* Use of any other blood pressure lowering medication for treatment of hypertension within 30 days of enrollment except calcium channel blockers and diuretics
* History or current clinical evidence of moderate-to-severe obstructive pulmonary disease or reactive airway diseases (i.e. asthma) requiring therapy
* Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times upper limit of institutional normal
* Gastrointestinal, or biliary disorders that could impair absorption, metabolism, or excretion of orally administered medications
* Endocrine disorders (such as primary aldosteronism, pheochromocytoma, hyper- or hypothyroidism) not controlled with medication
* Uncontrolled diabetes (controlled diabetes per the American Diabetes Association and International Diabetes Center's Glycemic Target Goals is hemoglobin A1C < 7%)
* Anemia (hematocrit < 28%)
* Currently using select CYP2D6 inhibitor or inducer medications
* Inability to swallow pills
* Female patients who are pregnant are not eligible; women of childbearing potential require a negative pregnancy test prior to starting study drug
* Lactating females are not eligible unless they have agreed to not breastfeed their infants
* Sexually active female patients of reproductive potential are not eligible unless they agree to use an effective contraceptive method during study and for 2 months after stopping the study drug; abstinence is an acceptable method of birth control
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/04/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
Accrual to date
Final
196
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [2] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
6008 - Perth
Recruitment postcode(s) [2] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Hawaii
Country [12] 0 0
United States of America
State/province [12] 0 0
Illinois
Country [13] 0 0
United States of America
State/province [13] 0 0
Indiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Iowa
Country [15] 0 0
United States of America
State/province [15] 0 0
Kentucky
Country [16] 0 0
United States of America
State/province [16] 0 0
Louisiana
Country [17] 0 0
United States of America
State/province [17] 0 0
Maryland
Country [18] 0 0
United States of America
State/province [18] 0 0
Michigan
Country [19] 0 0
United States of America
State/province [19] 0 0
Minnesota
Country [20] 0 0
United States of America
State/province [20] 0 0
Mississippi
Country [21] 0 0
United States of America
State/province [21] 0 0
Missouri
Country [22] 0 0
United States of America
State/province [22] 0 0
Nebraska
Country [23] 0 0
United States of America
State/province [23] 0 0
Nevada
Country [24] 0 0
United States of America
State/province [24] 0 0
New Jersey
Country [25] 0 0
United States of America
State/province [25] 0 0
New York
Country [26] 0 0
United States of America
State/province [26] 0 0
North Carolina
Country [27] 0 0
United States of America
State/province [27] 0 0
Ohio
Country [28] 0 0
United States of America
State/province [28] 0 0
Oklahoma
Country [29] 0 0
United States of America
State/province [29] 0 0
Oregon
Country [30] 0 0
United States of America
State/province [30] 0 0
Pennsylvania
Country [31] 0 0
United States of America
State/province [31] 0 0
South Carolina
Country [32] 0 0
United States of America
State/province [32] 0 0
Tennessee
Country [33] 0 0
United States of America
State/province [33] 0 0
Texas
Country [34] 0 0
United States of America
State/province [34] 0 0
Virginia
Country [35] 0 0
United States of America
State/province [35] 0 0
Washington
Country [36] 0 0
Canada
State/province [36] 0 0
Nova Scotia
Country [37] 0 0
New Zealand
State/province [37] 0 0
Auckland
Country [38] 0 0
New Zealand
State/province [38] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Saro H Armenian
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/07/NCT02717507/Prot_SAP_000.pdf
Statistical analysis plan Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/07/NCT02717507/Prot_SAP_000.pdf
Study protocol Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/07/NCT02717507/Prot_SAP_000.pdf
Statistical analysis plan Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/07/NCT02717507/Prot_SAP_000.pdf
Study protocol Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/07/NCT02717507/Prot_SAP_000.pdf
Statistical analysis plan Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/07/NCT02717507/Prot_SAP_000.pdf
Study protocol Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/07/NCT02717507/Prot_SAP_000.pdf
Statistical analysis plan Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/07/NCT02717507/Prot_SAP_000.pdf



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02717507