Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R21HL150723 | U.S. NIH Grant/Contract | View source | |
| 849569 | Other Grant/Funding Number | American Heart Association |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| American Heart Association | OTHER |
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Investigators will evaluate the safety, tolerability, and feasibility of a risk-guided cardioprotective treatment strategy with carvedilol, as compared to usual care, in breast cancer patients undergoing treatment with doxorubicin, trastuzumab, or the combination.
This is a single-center, randomized clinical trial that seeks to determine if a risk guided treatment strategy that initiates carvedilol in high risk breast cancer patients prior to doxorubicin and/or trastuzumab is safe, tolerable, and feasible. Subjects who are identified as having elevated CTX Risk by an internally validated clinical risk score (exceeding a pre-specified risk threshold) will be randomized to individually-dosed, open-label carvedilol or usual care. Investigators will use a stratified randomization according to trastuzumab therapy (yes/no) to ensure balance across treatment regimen. Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Carvedilol | Experimental | Carvedilol will be initiated at 3.125mg twice daily and uptitrated as tolerated in a stepwise fashion to a maximum dose of 25mg twice daily or to a systolic blood pressure (SBP) of 110-120mmHg or heart rate (HR) of 50-55 beats per minute (bpm). Patients will start carvedilol in the evening after first dose of chemotherapy and will continue on medication for 12 months. Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
|
| Usual Care | No Intervention | Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carvedilol | Drug | Individually dosed carvedilol |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Left Ventricular Ejection Fraction (LVEF) | LVEF by echocardiogram. Left ventricular ejection fraction (LVEF) is defined as the left ventricular stroke volume (left ventricular end diastolic volume minus the left ventricular end systolic volume) divided by the left ventricular end diastolic volume. This fraction is multiplied by 100 to yield the LVEF, and is defined as a % (the unit of measure) (J Am Soc Echocardiogr 2015;28:1-39.). 2D left ventricular volumes are estimated according to the biplane method of disks (modified Simpson's rule), as recommended by societal guidelines. Higher values are generally considered more favorable. | up to 24 months |
| Treatment Adherence as Measured by Pill Count | Rate of compliance with prescribed dose of carvedilol assessed based on pill count. Patients in the elevated-risk carvedilol group were asked to bring their study medications to all study visits and remaining pills were counted by the study coordinator to determine how many pills had been taken. Treatment adherence was calculated as the ratio of number of pills taken to expected number of pills taken, and is reported as a percentage. An adherence rate closer to 100 is better. Treatment adherence is reported only for those patients who were assigned to the elevated risk/carvedilol group, and therefore expected to take study medication. | 12 months |
| Adverse Events | Targeted Adverse Events were prospectively assessed according to the CTCAE v5.0. The number of patients experiencing any adverse event (Grade 2-5) was tabulated by risk group and by treatment arm during carvedilol intervention (baseline - 12 months). In the CTCAE, grade refers to the severity of the event. Grade 2 events are moderate, or have non-urgent/non-invasive intervention indicated, or limit age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 events are severe/medically significant but not immediately life-threatening, or have hospitalization or prolongation of hospitalization indicated, or limit self-care ADLs. Grade 4 events have life-threatening consequences or have urgent intervention indicated. Grade 5 indicates a death related to the adverse event. | Up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Diastolic Function (E/e') by Echocardiogram | E/e' is a measure of diastolic function derived from the ratio of the pulse wave Doppler interrogations of the mitral inflow at the mitral valve leaflet tips and at the lateral and septal mitral annulus via tissue Doppler imaging. This measure provided insight into myocardial relaxation, preload, and left ventricular filling pressures, with values > 14 indicative of elevated filling pressure. This is core-lab quantified, blinded to patient and treatment characteristics. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bonnie Ky, MD, MSCE | Perelman School of Medicine at the University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40172740 | Derived | Jung W, Hubbard RA, Smith AM, Ko K, Huang A, Wang J, Isaacs JM, Zhang L, Liu PP, Chen Z, Shah PD, Mintzer D, Bhattacharya S, Knollman HM, Clark AS, Koropeckyj-Cox D, Messinger M, Wilcox NS, Xia C, Narayan V, Upshaw JN, Armenian SH, Ky B. Risk-guided cardioprotection with carvedilol in patients with breast cancer (CCT guide): a phase 1 randomized clinical trial. Breast Cancer Res Treat. 2025 Jun;211(2):293-305. doi: 10.1007/s10549-025-07636-3. Epub 2025 Apr 2. |
Not provided
Not provided
Investigators do not plan to make the IPD, analytic methods, or study materials available to other researchers for purposes of reproducing our results or replicating the procedure given the pilot Phase 1 nature of this study.
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The cardiotoxicity risk score was calculated using Cox proportional hazards regression with race, systolic blood pressure, left ventricular ejection fraction, systemic cancer therapy, smoking status, diabetes and hypertension as selected predictors (PMID 4012740). A threshold of 4.5% risk of cardiac dysfunction at 1 year was set to prioritize sensitivity. 49 patients were classified as low risk and 19 as elevated risk. 13 elevated risk patients were randomized to carvedilol and 6 to usual care.
Not provided
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| ID | Title | Description |
|---|---|---|
| FG000 | Elevated Risk / Carvedilol | Patients determined to be elevated risk and randomized to carvedilol (elevated risk/carvedilol arm) initiated carvedilol at a dose of 3.125 mg twice daily on the evening of the first cancer therapy cycle and continued for 12 months. Dose adjustments were based on tolerability and targeted parameters as determined by the study physician, and carvedilol was titrated to maximum tolerated dose by the participant or to a SBP of 110-120mmHg or heart rate (HR) of 50-55 beats per minute. Titration steps were predefined at doses of 6.25 mg, 12.5 mg, and up to 25 mg twice daily. Clinical, echocardiographic, and biomarker data were collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9 12 and 24 months. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| 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 | Oct 1, 2021 |
Not provided
An internally validated CV risk score will be used to determine an individual patient's risk. Low risk patients will be observed and managed according to usual care. Elevated risk patients will be randomized to open label, individually dosed carvedilol for 1 year or usual care.
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| up to 24 months |
| Ventricular-arterial Coupling Measured by Echocardiogram | Ventricular-arterial (VA) coupling, the ratio between effective arterial elastance (Ea), indicative of load, and end-systolic elastance (Ees), indicative of LV contractility, was also quantified. Ea/Ees is a measure of cardiac efficiency, with normal values of 0.8-1.0, and lower numbers typically indicative of greater efficiency and higher values reflective of worse function. This is core-lab quantified, blinded to patient and treatment characteristics. | up to 24 months |
| Cardiac Strain Measurements by Echocardiogram | Global longitudinal strain (GLS, %) averaged from 3 apical views (left ventricular apical 4-chamber, 2-chamber, and 3-chamber) was obtained using speckle-tracking technology using Tomtec Imaging Systems. GLS is a more sensitive measure of cardiac function, with values greater than -16% (e.g., -15%) for GLS associated with worse outcomes. Circumferential strain (GCS, %) from the short axis view (mid left ventricle) was obtained using speckle-tracking technology using Tomtec Imaging Systems. Circumferential strain is a more sensitive measure of cardiac function, with values or greater than -20% (e.g., -19%) associated with worse outcomes. GLS and GCS are core-lab quantified, blinded to patient and treatment characteristics. | up to 24 months |
| Frequency of Individuals With Cardiac Dysfunction | Frequency of individuals with cardiac dysfunction, as defined by reduction in LVEF of >/= 10% to < 50%. | up to 24 months |
| High-sensitivity Troponin (hsTnT) Level | Change in the cardiac biomarker of injury hsTnT over time, defined as a continuous variable. hsTnT is a biomarker that is indicative of cardiac injury, with higher values associated with more severe injury. This is core-lab quantified, blinded to patient and treatment characteristics. | up to 24 months |
| N-terminal Pro B-type Natriuetic Peptide (NTproBNP) Level | Change in the cardiac biomarker, NT-proBNP over time, defined as a continuous variable. NTproBNP is a biomarker that is indicative of neurohormonal stress, with higher levels associated with more neurohormonal stress. This is core-lab quantified, blinded to patient and treatment characteristics. | up to 24 months |
| Left Ventricular Mass | LV mass by echocardiogram. Measurements of left ventricular mass (g) provided insight into cardiac structure, size, and remodeling. LV mass was calculated by the area-length method, as recommended by societal guidelines. This is core-lab quantified, blinded to patient and treatment characteristics. | up to 24 Months |
| FG001 | Elevated Risk/Usual Care | Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| FG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| 12 Month |
|
| 24 Month |
|
| COMPLETED |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Elevated Risk / Carvedilol | Patients determined to be elevated risk and randomized to carvedilol (elevated risk/carvedilol arm) initiated carvedilol at a dose of 3.125 mg twice daily on the evening of the first cancer therapy cycle and continued for 12 months. Dose adjustments were based on tolerability and targeted parameters as determined by the study physician, and carvedilol was titrated to maximum tolerated dose by the participant or to a SBP of 110-120mmHg or heart rate (HR) of 50-55 beats per minute. Titration steps were predefined at doses of 6.25 mg, 12.5 mg, and up to 25 mg twice daily. Clinical, echocardiographic, and biomarker data were collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9 12 and 24 months. |
| BG001 | Elevated Risk/Usual Care | Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| BG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Race and ethnicity were self-reported | Count of Participants | Participants | No |
| ||||||||||||||
| Race (NIH/OMB) | Race and ethnicity were self-reported. | Count of Participants | Participants | No |
| ||||||||||||||
| Systolic Blood Pressure (SBP) | Median | Inter-Quartile Range | mmHg |
| |||||||||||||||
| Left Ventricular Ejection Fraction (LVEF) | LVEF by echocardiogram. Left ventricular ejection fraction (LVEF) is defined as the left ventricular stroke volume (left ventricular end diastolic volume minus the left ventricular end systolic volume) divided by the left ventricular end diastolic volume. This fraction is multiplied by 100 to yield the LVEF, and is defined as a % (the unit of measure) (J Am Soc Echocardiogr 2015;28:1-39.). 2D left ventricular volumes are estimated according to the biplane method of disks (modified Simpson's rule), as recommended by societal guidelines. Higher values are generally considered more favorable. | Median | Inter-Quartile Range | percent |
| ||||||||||||||
| Systemic Cancer Therapy (Anthracyclines and Her2 targeted agents) | Patient received a systemic therapy regimen containing doxorubicin or Her2 targeted therapy or the combination. | Count of Participants | Participants |
| |||||||||||||||
| Smoking Status | Current and prior smokers | Count of Participants | Participants |
| |||||||||||||||
| Diabetes | Count of Participants | Participants |
| ||||||||||||||||
| Hypertension (HTN) | Patients were considered to have HTN at baseline if they had a diagnosis of hypertension, or were taking anti-hypertensives, or had systolic blood pressure > 140 on average over the 6 weeks prior to enrollment. | Count of Participants | Participants |
|
| 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 | Left Ventricular Ejection Fraction (LVEF) | LVEF by echocardiogram. Left ventricular ejection fraction (LVEF) is defined as the left ventricular stroke volume (left ventricular end diastolic volume minus the left ventricular end systolic volume) divided by the left ventricular end diastolic volume. This fraction is multiplied by 100 to yield the LVEF, and is defined as a % (the unit of measure) (J Am Soc Echocardiogr 2015;28:1-39.). 2D left ventricular volumes are estimated according to the biplane method of disks (modified Simpson's rule), as recommended by societal guidelines. Higher values are generally considered more favorable. | Exploratory cardiac efficacy by cardiac function (LVEF) was analyzed, evaluating the three groups according to the treatment the participants actually received ("as treated"). After randomization, three participants refused carvedilol but agreed to remain on study for follow-up, and one participant assigned to usual care started carvedilol for clinical indications at the baseline visit. As a result, there were 11 participants treated with carvedilol and 8 treated as per usual care. | Posted | Median | Inter-Quartile Range | percent | up to 24 months |
|
|
| ||||||||||||||||||||||||||||||||
| Primary | Treatment Adherence as Measured by Pill Count | Rate of compliance with prescribed dose of carvedilol assessed based on pill count. Patients in the elevated-risk carvedilol group were asked to bring their study medications to all study visits and remaining pills were counted by the study coordinator to determine how many pills had been taken. Treatment adherence was calculated as the ratio of number of pills taken to expected number of pills taken, and is reported as a percentage. An adherence rate closer to 100 is better. Treatment adherence is reported only for those patients who were assigned to the elevated risk/carvedilol group, and therefore expected to take study medication. | Adherence to the carvedilol intervention was calculated only among the elevated-risk carvedilol group. | Posted | Median | Full Range | percent of prescribed doses | 12 months |
| ||||||||||||||||||||||||||||||||||
| Primary | Adverse Events | Targeted Adverse Events were prospectively assessed according to the CTCAE v5.0. The number of patients experiencing any adverse event (Grade 2-5) was tabulated by risk group and by treatment arm during carvedilol intervention (baseline - 12 months). In the CTCAE, grade refers to the severity of the event. Grade 2 events are moderate, or have non-urgent/non-invasive intervention indicated, or limit age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 events are severe/medically significant but not immediately life-threatening, or have hospitalization or prolongation of hospitalization indicated, or limit self-care ADLs. Grade 4 events have life-threatening consequences or have urgent intervention indicated. Grade 5 indicates a death related to the adverse event. | Safety was analyzed, evaluating the three groups according to the treatment the participants actually received ("as treated"). After randomization, three participants refused carvedilol but agreed to remain on study for follow-up, and one participant assigned to usual care started carvedilol for clinical indications at the baseline visit. As a result, there were 11 participants treated with carvedilol and 8 treated as per usual care. | Posted | Count of Participants | Participants | Up to 12 months |
| |||||||||||||||||||||||||||||||||||
| Secondary | Diastolic Function (E/e') by Echocardiogram | E/e' is a measure of diastolic function derived from the ratio of the pulse wave Doppler interrogations of the mitral inflow at the mitral valve leaflet tips and at the lateral and septal mitral annulus via tissue Doppler imaging. This measure provided insight into myocardial relaxation, preload, and left ventricular filling pressures, with values > 14 indicative of elevated filling pressure. This is core-lab quantified, blinded to patient and treatment characteristics. | Exploratory cardiac efficacy by diastolic function was analyzed, evaluating the three groups according to the treatment the participants actually received ("as treated"). After randomization, three participants refused carvedilol but agreed to remain on study for follow-up, and one participant assigned to usual care started carvedilol for clinical indications at the baseline visit. As a result, there were 11 participants treated with carvedilol and 8 treated as per usual care. | Posted | Median | Inter-Quartile Range | ratio | up to 24 months |
| ||||||||||||||||||||||||||||||||||
| Secondary | Ventricular-arterial Coupling Measured by Echocardiogram | Ventricular-arterial (VA) coupling, the ratio between effective arterial elastance (Ea), indicative of load, and end-systolic elastance (Ees), indicative of LV contractility, was also quantified. Ea/Ees is a measure of cardiac efficiency, with normal values of 0.8-1.0, and lower numbers typically indicative of greater efficiency and higher values reflective of worse function. This is core-lab quantified, blinded to patient and treatment characteristics. | Exploratory cardiac efficacy by ventricular arterial coupling was analyzed, evaluating the three groups according to the treatment the participants actually received ("as treated"). After randomization, three participants refused carvedilol but agreed to remain on study for follow-up, and one participant assigned to usual care started carvedilol for clinical indications at the baseline visit. As a result, there were 11 participants treated with carvedilol and 8 treated as per usual care. | Posted | Median | Inter-Quartile Range | ratio | up to 24 months |
| ||||||||||||||||||||||||||||||||||
| Secondary | Cardiac Strain Measurements by Echocardiogram | Global longitudinal strain (GLS, %) averaged from 3 apical views (left ventricular apical 4-chamber, 2-chamber, and 3-chamber) was obtained using speckle-tracking technology using Tomtec Imaging Systems. GLS is a more sensitive measure of cardiac function, with values greater than -16% (e.g., -15%) for GLS associated with worse outcomes. Circumferential strain (GCS, %) from the short axis view (mid left ventricle) was obtained using speckle-tracking technology using Tomtec Imaging Systems. Circumferential strain is a more sensitive measure of cardiac function, with values or greater than -20% (e.g., -19%) associated with worse outcomes. GLS and GCS are core-lab quantified, blinded to patient and treatment characteristics. | Exploratory cardiac efficacy by longitudinal strain was analyzed, evaluating the three groups according to the treatment the participants actually received ("as treated"). After randomization, three participants refused carvedilol but agreed to remain on study for follow-up, and one participant assigned to usual care started carvedilol for clinical indications at the baseline visit. As a result, there were 11 participants treated with carvedilol and 8 treated as per usual care. | Posted | Median | Inter-Quartile Range | percent | up to 24 months |
| ||||||||||||||||||||||||||||||||||
| Secondary | Frequency of Individuals With Cardiac Dysfunction | Frequency of individuals with cardiac dysfunction, as defined by reduction in LVEF of >/= 10% to < 50%. | Exploratory cardiac efficacy was analyzed, evaluating the three groups according to the treatment the participants actually received ("as treated"). After randomization, three participants refused carvedilol but agreed to remain on study for follow-up, and one participant assigned to usual care started carvedilol for clinical indications at the baseline visit. As a result, there were 11 participants treated with carvedilol and 8 treated as per usual care. | Posted | Count of Participants | Participants | up to 24 months |
| |||||||||||||||||||||||||||||||||||
| Secondary | High-sensitivity Troponin (hsTnT) Level | Change in the cardiac biomarker of injury hsTnT over time, defined as a continuous variable. hsTnT is a biomarker that is indicative of cardiac injury, with higher values associated with more severe injury. This is core-lab quantified, blinded to patient and treatment characteristics. | Exploratory cardiac efficacy was analyzed, evaluating the three groups according to the treatment the participants actually received ("as treated"). After randomization, three participants refused carvedilol but agreed to remain on study for follow-up, and one participant assigned to usual care started carvedilol for clinical indications at the baseline visit. As a result, there were 11 participants treated with carvedilol and 8 treated as per usual care. | Posted | Median | Inter-Quartile Range | ng/L | up to 24 months |
| ||||||||||||||||||||||||||||||||||
| Secondary | N-terminal Pro B-type Natriuetic Peptide (NTproBNP) Level | Change in the cardiac biomarker, NT-proBNP over time, defined as a continuous variable. NTproBNP is a biomarker that is indicative of neurohormonal stress, with higher levels associated with more neurohormonal stress. This is core-lab quantified, blinded to patient and treatment characteristics. | Exploratory cardiac efficacy was analyzed, evaluating the three groups according to the treatment the participants actually received ("as treated"). After randomization, three participants refused carvedilol but agreed to remain on study for follow-up, and one participant assigned to usual care started carvedilol for clinical indications at the baseline visit. As a result, there were 11 participants treated with carvedilol and 8 treated as per usual care. | Posted | Median | Inter-Quartile Range | ng/L | up to 24 months |
| ||||||||||||||||||||||||||||||||||
| Secondary | Left Ventricular Mass | LV mass by echocardiogram. Measurements of left ventricular mass (g) provided insight into cardiac structure, size, and remodeling. LV mass was calculated by the area-length method, as recommended by societal guidelines. This is core-lab quantified, blinded to patient and treatment characteristics. | Exploratory cardiac efficacy was analyzed, evaluating the three groups according to the treatment the participants actually received ("as treated"). After randomization, three participants refused carvedilol but agreed to remain on study for follow-up, and one participant assigned to usual care started carvedilol for clinical indications at the baseline visit. As a result, there were 11 participants treated with carvedilol and 8 treated as per usual care. | Posted | Median | Inter-Quartile Range | g | up to 24 Months |
|
24 months
Adverse Events were assessed and graded according to the CTCAE v5.0. At each visit, patients were assessed for grade 2 and higher targeted adverse events (bradycardia, fatigue, and hypotension) as well as cardiovascular events and events ending in death using chart review and patient interview. All SAEs and AEs collected as part of the study and consistent with reporting requirements are reported.
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 | Elevated Risk / Carvedilol | Patients determined to be elevated risk and randomized to carvedilol (elevated risk/carvedilol arm) initiated carvedilol at a dose of 3.125 mg twice daily on the evening of the first cancer therapy cycle and continued for 12 months. Dose adjustments were based on tolerability and targeted parameters as determined by the study physician, and carvedilol was titrated to maximum tolerated dose by the participant or to a SBP of 110-120mmHg or heart rate (HR) of 50-55 beats per minute. Titration steps were predefined at doses of 6.25 mg, 12.5 mg, and up to 25 mg twice daily. Clinical, echocardiographic, and biomarker data were collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9 12 and 24 months. | 1 | 11 | 1 | 11 | 11 | 11 |
| EG001 | Elevated Risk/Usual Care | Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. | 0 | 8 | 0 | 8 | 8 | 8 |
| EG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. | 1 | 49 | 1 | 49 | 47 | 49 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disease Progression | General disorders | CTCAE (5.0) | Systematic Assessment | unrelated to intervention |
|
| Cardiac Arrest | Cardiac disorders | CTCAE (5.0) | Systematic Assessment | Unrelated to intervention (COVID-19 related) |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | CTCAE (5.0) | Systematic Assessment | Grade 2 and higher |
|
| Fatigue | General disorders | CTCAE (5.0) | Systematic Assessment | Grade 2 and higher |
|
| Ejection Fraction Decreased | Investigations | CTCAE (5.0) | Systematic Assessment | Grade 2 and higher |
|
| Electrocardiogram T Wave Abnormal | Investigations | CTCAE (5.0) | Systematic Assessment | Grade 2 and higher |
|
| Thromboembolic Event | Vascular disorders | CTCAE (5.0) | Systematic Assessment | Grade 2 and higher |
|
| Dizziness | Nervous system disorders | CTCAE (5.0) | Systematic Assessment | Grade 2 and higher |
|
| Hypotension | Vascular disorders | CTCAE (5.0) | Systematic Assessment | Grade 2 and higher |
|
| Myocardial Infarction | Cardiac disorders | CTCAE (5.0) | Systematic Assessment | Grade 2 and higher |
|
| Pre-Syncope | Nervous system disorders | CTCAE (5.0) | Systematic Assessment | Grade 2 and higher |
|
The limitations include small sample size and the fact that concomitant use of cardiac medications was not controlled. The study was executed during the COVID-19 pandemic which may have impacted patient recruitment and adherence.
Hypothesis testing was not conducted due to the limited sample size and exploratory nature of the study. Descriptive summary statistics were used to characterize the study population, outcome measures, and adverse events.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bonnie Ky, MD, MSCE | University of Pennsylvania | 215-573-6606 | bonnie.ky@pennmedicine.upenn.edu |
| Jul 1, 2025 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 22, 2024 | Jul 1, 2025 | ICF_001.pdf |
| ID | Term |
|---|---|
| D066126 | Cardiotoxicity |
| D001943 | Breast Neoplasms |
| D009202 | Cardiomyopathies |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077261 | Carvedilol |
| 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 |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Her2 Targeted |
|
| Doxorubicin + Her2 Targeted |
|
|
| 24 Month |
|
| OG001 | Elevated Risk/Usual Care | Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| OG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
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| OG001 | Elevated Risk/Usual Care | Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| OG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
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| OG001 | Elevated Risk/Usual Care | Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| OG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
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| OG001 | Elevated Risk/Usual Care | Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| OG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
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| OG001 | Elevated Risk/Usual Care | Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| OG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
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Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| OG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
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| OG001 | Elevated Risk/Usual Care | Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| OG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
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| OG001 | Elevated Risk/Usual Care | Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| OG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
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| OG001 |
| Elevated Risk/Usual Care |
Patients with elevated risk who were randomized to the Elevated Risk/Usual Care arm were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
| OG002 | Low Risk / Non-randomized | Patients who did not meet the threshold for elevated risk were not randomized, but were followed with clinical, echocardiographic, and biomarker data collected at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months. |
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