Trial Outcomes & Findings for Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors (NCT NCT02717507)

NCT ID: NCT02717507

Last Updated: 2025-04-23

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 196 participants
• Primary outcome timeframe: Baseline before treatment, 6 months, 12 months, 18 months, 24 months after treatment initiation
• Results posted on: 2025-04-23

Participant Flow

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)

Participant milestones

Measure	Arm I (Carvedilol) Patients receive low-dose carvedilol orally (PO) once daily (QD) or twice daily (BID) for 24 months.	Arm II (Placebo) Patients receive placebo PO QD or BID for 24 months.
Overall Study STARTED	89	93
Overall Study 2nd Timepoint Assessment of Echocardiology Required to be Analyzable	75	76
Overall Study COMPLETED	58	55
Overall Study NOT COMPLETED	31	38

Reasons for withdrawal

Measure	Arm I (Carvedilol) Patients receive low-dose carvedilol orally (PO) once daily (QD) or twice daily (BID) for 24 months.	Arm II (Placebo) Patients receive placebo PO QD or BID for 24 months.
Overall Study Lost to Follow-up	5	8
Overall Study Pregnancy	1	1
Overall Study Protocol Violation	2	2
Overall Study Withdrawal by Subject	20	20
Overall Study Relapse	1	1
Overall Study Cardiac Event	2	6

Baseline Characteristics

Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors

Baseline characteristics by cohort

Measure	Arm I (Carvedilol) n=89 Participants Patients receive low-dose carvedilol orally (PO) once daily (QD) or twice daily (BID) for 24 months.	Arm II (Placebo) n=93 Participants Patients receive placebo PO QD or BID for 24 months.	Total n=182 Participants Total of all reporting groups
Age, Categorical <=18 years	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	74 Participants n=5 Participants	77 Participants n=7 Participants	151 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	26.9 years STANDARD_DEVIATION 10.3 • n=5 Participants	27.7 years STANDARD_DEVIATION 10.1 • n=7 Participants	27.3 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	48 Participants n=7 Participants	91 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	45 Participants n=7 Participants	91 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	65 Participants n=5 Participants	69 Participants n=7 Participants	134 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	77 Participants n=5 Participants	82 Participants n=7 Participants	159 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	89 participants n=5 Participants	93 participants n=7 Participants	182 participants n=5 Participants

PRIMARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz) BL	-0.1372 z-score Standard Error 0.1711	-0.0893 z-score Standard Error 0.1917
Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz) 6m	-0.2167 z-score Standard Error 0.167	0.3215 z-score Standard Error 0.154
Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz) 12m	-0.2416 z-score Standard Error 0.1721	-0.2367 z-score Standard Error 0.1822
Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz) 18m	-0.2375 z-score Standard Error 0.21	-0.1974 z-score Standard Error 0.1976
Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz) 24m	0.0213 z-score Standard Error 0.2353	-0.1834 z-score Standard Error 0.2145

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Left Ventricular End-systolic Wall Stress BL	93.2892 g/cm^2 Standard Error 2.222	90.6135 g/cm^2 Standard Error 2.9775
Average Left Ventricular End-systolic Wall Stress 6m	90.3088 g/cm^2 Standard Error 2.0577	96.8356 g/cm^2 Standard Error 2.9025
Average Left Ventricular End-systolic Wall Stress 12m	88.984 g/cm^2 Standard Error 2.0069	96.0616 g/cm^2 Standard Error 3.0406
Average Left Ventricular End-systolic Wall Stress 18m	93.9267 g/cm^2 Standard Error 2.4333	91.6458 g/cm^2 Standard Error 3.1257
Average Left Ventricular End-systolic Wall Stress 24m	89.2513 g/cm^2 Standard Error 2.4341	94.0647 g/cm^2 Standard Error 3.6562

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Left Ventricular End-systolic Dimension BL	03.2765 centimeter Standard Error 0.043	3.2396 centimeter Standard Error 0.0459
Average Left Ventricular End-systolic Dimension 6m	3.2901 centimeter Standard Error 0.0382	3.3023 centimeter Standard Error 0.0442
Average Left Ventricular End-systolic Dimension 12m	3.262 centimeter Standard Error 0.043	3.2964 centimeter Standard Error 0.0571
Average Left Ventricular End-systolic Dimension 18m	3.32 centimeter Standard Error 0.0436	3.2798 centimeter Standard Error 0.0579
Average Left Ventricular End-systolic Dimension 24m	3.2441 centimeter Standard Error 0.0435	3.286 centimeter Standard Error 0.0607

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Left Ventricular End-systolic Volume BL	42.2193 ml Standard Error 1.3907	39.7354 ml Standard Error 1.3633
Average Left Ventricular End-systolic Volume 6m	41.6128 ml Standard Error 1.4041	41.3839 ml Standard Error 1.5337
Average Left Ventricular End-systolic Volume 12m	42.8437 ml Standard Error 1.3498	41.8113 ml Standard Error 1.6275
Average Left Ventricular End-systolic Volume 18m	43.1453 ml Standard Error 1.605	42.5634 ml Standard Error 2.1281
Average Left Ventricular End-systolic Volume 24m	42.0086 ml Standard Error 1.7268	42.442 ml Standard Error 2.3661

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Left Ventricular End-diastolic Dimension BL	4.5836 cm Standard Error 0.0501	4.5269 cm Standard Error 0.0565
Average Left Ventricular End-diastolic Dimension 6m	4.6035 cm Standard Error 0.0431	4.565 cm Standard Error 0.0463
Average Left Ventricular End-diastolic Dimension 12m	4.636 cm Standard Error 0.0556	4.5884 cm Standard Error 0.0768
Average Left Ventricular End-diastolic Dimension 18m	4.6032 cm Standard Error 0.0568	4.5462 cm Standard Error 0.0663
Average Left Ventricular End-diastolic Dimension 24	4.5147 cm Standard Error 0.0614	4.5976 cm Standard Error 0.067

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Left Ventricular End-diastolic Volume BL	99.7507 ml Standard Error 3.0157	93.3155 ml Standard Error 3.0337
Average Left Ventricular End-diastolic Volume 6m	99.3216 ml Standard Error 2.9788	95.7434 ml Standard Error 3.2631
Average Left Ventricular End-diastolic Volume 12m	102.378 ml Standard Error 2.975	96.5002 ml Standard Error 3.3889
Average Left Ventricular End-diastolic Volume 18m	101.174 ml Standard Error 3.5977	99.4656 ml Standard Error 4.0815
Average Left Ventricular End-diastolic Volume 24m	100.659 ml Standard Error 4.0356	98.9602 ml Standard Error 4.6469

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Left Ventricular Mass BL	57.4862 g/m^2 Standard Error 1.2135	57.9322 g/m^2 Standard Error 1.5767
Average Left Ventricular Mass 6m	58.2839 g/m^2 Standard Error 1.3859	57.0924 g/m^2 Standard Error 1.29
Average Left Ventricular Mass 12m	60.2116 g/m^2 Standard Error 1.6786	59.4508 g/m^2 Standard Error 1.4995
Average Left Ventricular Mass 18m	57.7053 g/m^2 Standard Error 1.6667	59.1793 g/m^2 Standard Error 1.6168
Average Left Ventricular Mass 24m	58.3315 g/m^2 Standard Error 1.6478	59.1026 g/m^2 Standard Error 1.8092

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

A measure to assess preload and afterload (in %). The mean is reported by arm at each timepoint with corresponding standard errors.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Fractional Shortening BL	28.5362 percent Standard Error 0.4549	28.4339 percent Standard Error 0.4764
Average Fractional Shortening 6m	28.5409 percent Standard Error 0.4738	27.6866 percent Standard Error 0.5799
Average Fractional Shortening 12m	29.6121 percent Standard Error 0.483	28.1085 percent Standard Error 0.4918
Average Fractional Shortening 18m	27.8219 percent Standard Error 0.4951	27.8891 percent Standard Error 0.596
Average Fractional Shortening 24	28.0302 percent Standard Error 0.5073	28.5953 percent Standard Error 0.5901

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Ejection Fraction BL	57.6 Percent Standard Error 0.69	57.42 Percent Standard Error 0.58
Average Ejection Fraction 6m	58.16 Percent Standard Error 0.59	56.84 Percent Standard Error 0.6
Average Ejection Fraction 12m	58.07 Percent Standard Error 0.62	56.61 Percent Standard Error 0.7
Average Ejection Fraction 18m	57.35 Percent Standard Error 0.69	57.6 Percent Standard Error 0.71
Average Ejection Fraction 24	58.16 Percent Standard Error 0.79	57.5 Percent Standard Error 0.62

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Peak Early Atrial Divided by Peak Late Atrial Velocities BL	1.728 ratio Standard Error 0.067	1.732 ratio Standard Error 0.071
Average Peak Early Atrial Divided by Peak Late Atrial Velocities 6m	1.642 ratio Standard Error 0.048	1.769 ratio Standard Error 0.069
Average Peak Early Atrial Divided by Peak Late Atrial Velocities 12m	1.723 ratio Standard Error 0.065	1.722 ratio Standard Error 0.079
Average Peak Early Atrial Divided by Peak Late Atrial Velocities 18m	1.732 ratio Standard Error 0.063	1.732 ratio Standard Error 0.081
Average Peak Early Atrial Divided by Peak Late Atrial Velocities 24m	1.603 ratio Standard Error 0.063	1.64 ratio Standard Error 0.074

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average N-terminal Pro B-type Natriuretic Peptide BL	27.3836 pg/mL Standard Error 2.0697	31.4324 pg/mL Standard Error 3.424
Average N-terminal Pro B-type Natriuretic Peptide 6m	31.8406 pg/mL Standard Error 3.3339	34.1857 pg/mL Standard Error 3.4737
Average N-terminal Pro B-type Natriuretic Peptide 12m	26.8203 pg/mL Standard Error 3.4625	33.2941 pg/mL Standard Error 4.095
Average N-terminal Pro B-type Natriuretic Peptide 18m	35.807 pg/mL Standard Error 3.7939	32.2807 pg/mL Standard Error 4.0405
Average N-terminal Pro B-type Natriuretic Peptide 24m	34.625 pg/mL Standard Error 3.0875	33.3774 pg/mL Standard Error 3.6481

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Cardiac N-terminal Pro B-type Natriuretic Peptide BL	85.6301 pg/mL Standard Error 13.3731	115.7222 pg/mL Standard Error 22.243
Average Cardiac N-terminal Pro B-type Natriuretic Peptide 6m	90.7536 pg/mL Standard Error 11.7877	128.9565 pg/mL Standard Error 23.736
Average Cardiac N-terminal Pro B-type Natriuretic Peptide 12m	87.7167 pg/mL Standard Error 13.38	115.6364 pg/mL Standard Error 26.823
Average Cardiac N-terminal Pro B-type Natriuretic Peptide 18m	99.4912 pg/mL Standard Error 15.7275	93.2105 pg/mL Standard Error 18.5618
Average Cardiac N-terminal Pro B-type Natriuretic Peptide 24m	101.8333 pg/mL Standard Error 14.2521	107.8490 pg/mL Standard Error 26.6515

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Cardiac Troponin I BL	0.00446 ng/mL Standard Error 0.0024	0.0011 ng/mL Standard Error 0.0008
Average Cardiac Troponin I 6m	0.00265 ng/mL Standard Error 0.001	0.00174 ng/mL Standard Error 0.0009
Average Cardiac Troponin I 12m	0.00467 ng/mL Standard Error 0.0014	0.00742 ng/mL Standard Error 0.0034
Average Cardiac Troponin I 18m	0.00737 ng/mL Standard Error 0.0017	0.00684 ng/mL Standard Error 0.0017
Average Cardiac Troponin I 24m	0.01111 ng/mL Standard Error 0.002	0.01132 ng/mL Standard Error 0.002

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Galectin-3 BL	4.4464 ng/mL Standard Error 0.2625	5.2538 ng/mL Standard Error 0.6531
Average Galectin-3 6m	4.3252 ng/mL Standard Error 0.2519	4.3735 ng/mL Standard Error 0.2746
Average Galectin-3 12m	3.7345 ng/mL Standard Error 0.234	4.3415 ng/mL Standard Error 0.327
Average Galectin-3 18m	3.4548 ng/mL Standard Error 0.2482	4.0214 ng/mL Standard Error 0.2506
Average Galectin-3 24m	3.8073 ng/mL Standard Error 0.3099	4.0791 ng/mL Standard Error 0.2853

SECONDARY outcome

Timeframe: From baseline to month 24 since baseline

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Proportion of Patients With Reportable Adverse Events as Described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).	0.0267 Proportion of patients with AE Interval 0.0083 to 0.1125	0 Proportion of patients with AE Interval 0.0 to 0.039

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

A liver function measurement (in mg/dL). The mean is reported by arm at each timepoint with corresponding standard errors.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Bilirubin BL	0.5634 mg/dL Standard Error 0.0428	0.4989 mg/dL Standard Error 0.0272
Average Bilirubin 6m	0.5973 mg/dL Standard Error 0.0453	0.4942 mg/dL Standard Error 0.0262
Average Bilirubin 12m	0.563 mg/dL Standard Error 0.0487	0.4969 mg/dL Standard Error 0.0302
Average Bilirubin 18m	0.593 mg/dL Standard Error 0.0665	0.507 mg/dL Standard Error 0.04
Average Bilirubin 24m	0.5561 mg/dL Standard Error 0.0436	0.5449 mg/dL Standard Error 0.0354

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Aspartate Aminotransferase 12m	25.426 IU/L Standard Error 1.423	27.014 IU/L Standard Error 1.432
Average Aspartate Aminotransferase BL	26.608 IU/L Standard Error 1.726	25.773 IU/L Standard Error 1.089
Average Aspartate Aminotransferase 6m	24.068 IU/L Standard Error 1.293	26.342 IU/L Standard Error 1.252
Average Aspartate Aminotransferase 18m	24.375 IU/L Standard Error 1.637	28.411 IU/L Standard Error 2.665
Average Aspartate Aminotransferase 24m	24.561 IU/L Standard Error 1.488	27.038 IU/L Standard Error 1.509

SECONDARY outcome

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

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Average Alanine Aminotransferase BL	29.122 IU/L Standard Error 2.31	30.467 IU/L Standard Error 1.948
Average Alanine Aminotransferase 6m	28.014 IU/L Standard Error 2.533	32.158 IU/L Standard Error 2.516
Average Alanine Aminotransferase 12m	30.148 IU/L Standard Error 2.985	31.155 IU/L Standard Error 2.742
Average Alanine Aminotransferase 18m	27.196 IU/L Standard Error 2.645	30.536 IU/L Standard Error 3.567
Average Alanine Aminotransferase 24m	29.86 IU/L Standard Error 3.064	29.245 IU/L Standard Error 2.626

SECONDARY outcome

Timeframe: Average adherence across 6 months, 12 months, 18 months, 24 months after treatment initiation are calculated.

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
Proportion of Participants With Average Adherence > 90%	0.483 proportion of participants Interval 0.378 to 0.588	0.517 proportion of participants Interval 0.412 to 0.622

SECONDARY outcome

Timeframe: Responses at days 14 to 730 were combined

Population: We excluded 31 participants who did not have a second time point assessment of echocardiography, resulting in 151 analyzable participants.

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.

Outcome measures

Measure	Arm I (Carvedilol) n=75 Participants Patients received Carvedilol PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.	Arm II (Placebo) n=76 Participants Patients received Placebo PO delivered at 6.25 mg twice daily (for a total dose of 12.5 mg per day) for 24 months.
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. Diarrhea	0.0533 Proportion of patients Interval 0.0025 to 0.1042	0.1316 Proportion of patients Interval 0.0556 to 0.2076
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. Skin rash	0.0933 Proportion of patients Interval 0.0025 to 0.1042	0.0789 Proportion of patients Interval 0.0183 to 0.1396
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. Itchy skin	0.1467 Proportion of patients Interval 0.0666 to 0.2267	0.1447 Proportion of patients Interval 0.0656 to 0.2238
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. Dry Mouth	0.0667 Proportion of patients Interval 0.0102 to 0.1231	0.1711 Proportion of patients Interval 0.0864 to 0.2557
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. Easy bruising	0.0133 Proportion of patients Interval 0.0 to 0.0393	0.0921 Proportion of patients Interval 0.0271 to 0.1571
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. Nosebleeds	0.0667 Proportion of patients Interval 0.0102 to 0.1231	0.0526 Proportion of patients Interval 0.0024 to 0.1028
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. Sunburn easily	0.0933 Proportion of patients Interval 0.0275 to 0.1592	0.0526 Proportion of patients Interval 0.0024 to 0.1028
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. Weight gain	0.0533 Proportion of patients Interval 0.0025 to 0.1042	0.0789 Proportion of patients Interval 0.0183 to 0.1396
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. Fluid retention	0.0267 Proportion of patients Interval 0.0 to 0.0631	0.0395 Proportion of patients Interval 0.0 to 0.0833
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. Swollen feet	0 Proportion of patients Interval 0.0 to 0.048	0.0921 Proportion of patients Interval 0.0271 to 0.1571
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. Increased sweating	0.0933 Proportion of patients Interval 0.0275 to 0.1592	0.0789 Proportion of patients Interval 0.0183 to 0.1396
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. Feeling weak in parts of your body	0.0933 Proportion of patients Interval 0.0275 to 0.1592	0.1316 Proportion of patients Interval 0.0556 to 0.2076
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. Shortness of breath or wheezing	0.0933 Proportion of patients Interval 0.0275 to 0.1592	0.0395 Proportion of patients Interval 0.0 to 0.0833
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. Chest pain or heaviness	0.08 Proportion of patients Interval 0.0186 to 0.1414	0.0921 Proportion of patients Interval 0.0271 to 0.1571
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. Heart racing or skipping beats	0.08 Proportion of patients Interval 0.0186 to 0.1414	0.0395 Proportion of patients Interval 0.0 to 0.0833
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. Feeling shaky or having tremors	0.0533 Proportion of patients Interval 0.0025 to 0.1042	0.0789 Proportion of patients Interval 0.0183 to 0.1396
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. Decreased bodily movement	0.0133 Proportion of patients Interval 0.0 to 0.0393	0.0395 Proportion of patients Interval 0.0 to 0.0833
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. Feeling nervous	0.1467 Proportion of patients Interval 0.0666 to 0.2267	0.1711 Proportion of patients Interval 0.0864 to 0.2557
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. Feeling downhearted, sad, and/or tearful	0.2 Proportion of patients Interval 0.1095 to 0.2905	0.1184 Proportion of patients Interval 0.0458 to 0.1911
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. Mood swings	0.12 Proportion of patients Interval 0.0465 to 0.1935	0.0921 Proportion of patients Interval 0.0271 to 0.1571
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. Dizziness and/or lightheadedness	0.16 Proportion of patients Interval 0.077 to 0.243	0.1316 Proportion of patients Interval 0.0556 to 0.2076
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. Dizziness upon standing (from sitting or lying down)	0.1467 Proportion of patients Interval 0.0666 to 0.2267	0.1579 Proportion of patients Interval 0.0759 to 0.2399
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. Insomnia	0.1733 Proportion of patients Interval 0.0877 to 0.259	0.1711 Proportion of patients Interval 0.0864 to 0.2557
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. Difficulty concentrating	0.1067 Proportion of patients Interval 0.0368 to 0.1765	0.1316 Proportion of patients Interval 0.0556 to 0.2076
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. Interrupted sleep	0.2 Proportion of patients Interval 0.1095 to 0.2905	0.2105 Proportion of patients Interval 0.1189 to 0.3022
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. Tendency to take naps	0.12 Proportion of patients Interval 0.0465 to 0.1935	0.1053 Proportion of patients Interval 0.0363 to 0.1743
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. Feeling unusually tired	0.2267 Proportion of patients Interval 0.1319 to 0.3214	0.2237 Proportion of patients Interval 0.13 to 0.3174
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. Falling asleep at inappropriate times	0.0267 Proportion of patients Interval 0.0 to 0.0631	0.0395 Proportion of patients Interval 0.0 to 0.0833
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. Ringing in the ears	0.0533 Proportion of patients Interval 0.0025 to 0.1042	0.0921 Proportion of patients Interval 0.0271 to 0.1571
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. Difficulty breathing	0.0267 Proportion of patients Interval 0.0 to 0.0631	0 Proportion of patients Interval 0.0 to 0.0474
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. Sensation that I have to urinate much of the time	0.0667 Proportion of patients Interval 0.0102 to 0.1231	0.0789 Proportion of patients Interval 0.0183 to 0.1396
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. Discoloration of urine (i.e., bloody)	0 Proportion of patients Interval 0.0 to 0.048	0.0395 Proportion of patients Interval 0.0 to 0.0833
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. Decreased libido	0.0667 Proportion of patients Interval 0.0102 to 0.1231	0.0526 Proportion of patients Interval 0.0024 to 0.1028
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. Unusually heavy menstrual flows (N/A if postmenopausal or male)	0.2 Proportion of patients Interval 0.0432 to 0.3568	0.111 Proportion of patients Interval 0.0 to 0.23

Adverse Events

Arm I (Carvedilol)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Arm II (Placebo)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Arm I (Carvedilol) n=89 participants at risk Patients receive low-dose carvedilol orally (PO) once daily (QD) or twice daily (BID) for 24 months.	Arm II (Placebo) n=93 participants at risk Patients receive placebo PO QD or BID for 24 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.1% 1/89 • 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.	0.00% 0/93 • 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.
Musculoskeletal and connective tissue disorders Arthralgia	1.1% 1/89 • 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.	0.00% 0/93 • 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.

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 16264470064

Email: resultsreportingcoordinator@childrensoncologygroup.org

Results disclosure agreements

• Principal investigator is a sponsor employee Must obtain prior Sponsor approval
• Publication restrictions are in place

Restriction type: OTHER