Trial Outcomes & Findings for PROactive Evaluation of Function to Avoid CardioToxicity (NCT NCT03862131)
NCT ID: NCT03862131
Last Updated: 2025-07-29
Results Overview
The area under the curve refers to the area under the curve of Receiver operating characteristic curves (ROC AUC) to evaluate the accuracy of MyoStrain® to detect cardiotoxicity compared to Cardiovascular Magnetic Resonance (CMR) Imaging standard measurements. * Myocardial dysfunction was defined as the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \> 10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL. * In patients with LVEF \< 53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \> 10% or a HF hospitalization. * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \>199 pg/mL.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
49 participants
Primary outcome timeframe
Through 36 months
Results posted on
2025-07-29
Participant Flow
Participant milestones
| Measure |
MyoStrain® Unblinded Treatment Arm
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group
* The unblinded treatment arm will enhance patient management by augmenting standard of care with serial MyoStrain® monitoring of the impact of cancer therapy on myocardial function.
* Higher Risk unblinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
MyoStrain® Blinded Control Arm
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk group
* The blinded control arm will provide investigators with LVEF and LVEDV/LVESV measurements, which are clinical, in conjunction with standard of care
* Higher Risk blinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
Non-randomized
-Patients were enrolled but not randomized to either arm.
|
|---|---|---|---|
|
Overall Study
STARTED
|
25
|
18
|
6
|
|
Overall Study
COMPLETED
|
15
|
10
|
0
|
|
Overall Study
NOT COMPLETED
|
10
|
8
|
6
|
Reasons for withdrawal
| Measure |
MyoStrain® Unblinded Treatment Arm
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group
* The unblinded treatment arm will enhance patient management by augmenting standard of care with serial MyoStrain® monitoring of the impact of cancer therapy on myocardial function.
* Higher Risk unblinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
MyoStrain® Blinded Control Arm
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk group
* The blinded control arm will provide investigators with LVEF and LVEDV/LVESV measurements, which are clinical, in conjunction with standard of care
* Higher Risk blinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
Non-randomized
-Patients were enrolled but not randomized to either arm.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
1
|
|
Overall Study
Determined to be ineligible
|
0
|
0
|
5
|
|
Overall Study
Death
|
4
|
4
|
0
|
|
Overall Study
Withdrawal by Subject
|
5
|
3
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
0
|
Baseline Characteristics
PROactive Evaluation of Function to Avoid CardioToxicity
Baseline characteristics by cohort
| Measure |
MyoStrain® Unblinded Treatment Arm
n=25 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group
* The unblinded treatment arm will enhance patient management by augmenting standard of care with serial MyoStrain® monitoring of the impact of cancer therapy on myocardial function.
* Higher Risk unblinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
MyoStrain® Blinded Control Arm
n=18 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk group
* The blinded control arm will provide investigators with LVEF and LVEDV/LVESV measurements, which are clinical, in conjunction with standard of care
* Higher Risk blinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
Non-randomized
n=6 Participants
-Patients were enrolled but not randomized to either arm.
|
Total
n=49 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
55 years
n=39 Participants
|
58.5 years
n=41 Participants
|
48.5 years
n=35 Participants
|
55 years
n=31 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=39 Participants
|
11 Participants
n=41 Participants
|
5 Participants
n=35 Participants
|
36 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=39 Participants
|
7 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
13 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
25 Participants
n=39 Participants
|
17 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
48 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
5 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=39 Participants
|
18 Participants
n=41 Participants
|
5 Participants
n=35 Participants
|
44 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=39 Participants
|
18 participants
n=41 Participants
|
6 participants
n=35 Participants
|
49 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Through 36 monthsThe area under the curve refers to the area under the curve of Receiver operating characteristic curves (ROC AUC) to evaluate the accuracy of MyoStrain® to detect cardiotoxicity compared to Cardiovascular Magnetic Resonance (CMR) Imaging standard measurements. * Myocardial dysfunction was defined as the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \> 10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL. * In patients with LVEF \< 53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \> 10% or a HF hospitalization. * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \>199 pg/mL.
Outcome measures
| Measure |
MyoStrain® Unblinded Treatment Arm
n=25 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group
* The unblinded treatment arm will enhance patient management by augmenting standard of care with serial MyoStrain® monitoring of the impact of cancer therapy on myocardial function.
* Higher Risk unblinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
MyoStrain® Blinded Control Arm
n=18 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk group
* The blinded control arm will provide investigators with LVEF and LVEDV/LVESV measurements, which are clinical, in conjunction with standard of care
* Higher Risk blinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
Combined MyoStrain® Control Arm and Treatment Arm
n=43 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group.
* After meeting eligibility criteria, patients will be further randomized to an unblinded arm (MyoStrain® measured and available to the treatment team) and a blinded arm (MyoStrain® measured but not available to the treatment team). This randomization will aid in an exploratory aim of testing the feasibility of MyoStrain® to guide cardioprotective therapy in the unblinded vs blinded arms. However, as all patients will have MyoStrain® measured, all patients (both treatment arms) will be combined for testing the primary outcome measure.
|
|---|---|---|---|
|
ROC AUC of MyoStrain® Compared to Standard CMR Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
MyoStrain®
|
0.876 probability
Interval 0.77 to 0.982
|
0.853 probability
Interval 0.728 to 0.978
|
0.864 probability
Interval 0.783 to 0.946
|
|
ROC AUC of MyoStrain® Compared to Standard CMR Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR LVEF
|
0.603 probability
Interval 0.456 to 0.749
|
0.790 probability
Interval 0.648 to 0.933
|
0.679 probability
Interval 0.573 to 0.786
|
|
ROC AUC of MyoStrain® Compared to Standard CMR Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular end-diastolic indexed (LVEDVI)
|
0.522 probability
Interval 0.377 to 0.666
|
0.532 probability
Interval 0.37 to 0.693
|
0.515 probability
Interval 0.408 to 0.622
|
|
ROC AUC of MyoStrain® Compared to Standard CMR Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular end-systolic volume index (LVESVI)
|
0.501 probability
Interval 0.358 to 0.645
|
0.689 probability
Interval 0.531 to 0.847
|
0.589 probability
Interval 0.481 to 0.698
|
|
ROC AUC of MyoStrain® Compared to Standard CMR Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular stroke volume index (LVSVI)
|
0.574 probability
Interval 0.428 to 0.721
|
0.693 probability
Interval 0.535 to 0.85
|
0.627 probability
Interval 0.519 to 0.735
|
PRIMARY outcome
Timeframe: Through 36 monthsSensitivity is defined as the number of true positives divided by the number of true positives + number of false negatives. * Myocardial dysfunction was defined as the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \> 10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL. * In patients with LVEF \< 53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \> 10% or a HF hospitalization. * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \>199 pg/mL
Outcome measures
| Measure |
MyoStrain® Unblinded Treatment Arm
n=25 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group
* The unblinded treatment arm will enhance patient management by augmenting standard of care with serial MyoStrain® monitoring of the impact of cancer therapy on myocardial function.
* Higher Risk unblinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
MyoStrain® Blinded Control Arm
n=18 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk group
* The blinded control arm will provide investigators with LVEF and LVEDV/LVESV measurements, which are clinical, in conjunction with standard of care
* Higher Risk blinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
Combined MyoStrain® Control Arm and Treatment Arm
n=43 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group.
* After meeting eligibility criteria, patients will be further randomized to an unblinded arm (MyoStrain® measured and available to the treatment team) and a blinded arm (MyoStrain® measured but not available to the treatment team). This randomization will aid in an exploratory aim of testing the feasibility of MyoStrain® to guide cardioprotective therapy in the unblinded vs blinded arms. However, as all patients will have MyoStrain® measured, all patients (both treatment arms) will be combined for testing the primary outcome measure.
|
|---|---|---|---|
|
Sensitivity of MyoStrain® Compared to CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
MyoStrain®
|
83.3 percent sensitivity
Interval 66.1 to 100.0
|
66.7 percent sensitivity
Interval 42.8 to 90.5
|
84.8 percent sensitivity
Interval 78.3 to 94.6
|
|
Sensitivity of MyoStrain® Compared to CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR LVEF
|
33.3 percent sensitivity
Interval 11.6 to 55.1
|
53.3 percent sensitivity
Interval 28.1 to 78.6
|
42.4 percent sensitivity
Interval 25.6 to 59.3
|
|
Sensitivity of MyoStrain® Compared to CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular end-diastolic indexed (LVEDVI)
|
44.4 percent sensitivity
Interval 21.5 to 67.4
|
66.7 percent sensitivity
Interval 42.8 to 90.5
|
48.5 percent sensitivity
Interval 31.4 to 65.5
|
|
Sensitivity of MyoStrain® Compared to CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular end-systolic volume index (LVESVI)
|
22.2 percent sensitivity
Interval 3.0 to 41.4
|
66.7 percent sensitivity
Interval 42.8 to 90.5
|
45.5 percent sensitivity
Interval 28.5 to 62.4
|
|
Sensitivity of MyoStrain® Compared to CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular stroke volume index (LVSVI)
|
33.3 percent sensitivity
Interval 11.6 to 55.1
|
93.3 percent sensitivity
Interval 80.7 to 100.0
|
33.3 percent sensitivity
Interval 17.2 to 49.4
|
PRIMARY outcome
Timeframe: Through 36 monthsSpecificity is defined as the number of true negatives divided by the number of true negatives + number of false positives. * Myocardial dysfunction was defined as the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \> 10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL. * In patients with LVEF \< 53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \> 10% or a HF hospitalization. * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \> 199 pg/mL
Outcome measures
| Measure |
MyoStrain® Unblinded Treatment Arm
n=25 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group
* The unblinded treatment arm will enhance patient management by augmenting standard of care with serial MyoStrain® monitoring of the impact of cancer therapy on myocardial function.
* Higher Risk unblinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
MyoStrain® Blinded Control Arm
n=18 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk group
* The blinded control arm will provide investigators with LVEF and LVEDV/LVESV measurements, which are clinical, in conjunction with standard of care
* Higher Risk blinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
Combined MyoStrain® Control Arm and Treatment Arm
n=43 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group.
* After meeting eligibility criteria, patients will be further randomized to an unblinded arm (MyoStrain® measured and available to the treatment team) and a blinded arm (MyoStrain® measured but not available to the treatment team). This randomization will aid in an exploratory aim of testing the feasibility of MyoStrain® to guide cardioprotective therapy in the unblinded vs blinded arms. However, as all patients will have MyoStrain® measured, all patients (both treatment arms) will be combined for testing the primary outcome measure.
|
|---|---|---|---|
|
Specificity of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
MyoStrain®
|
77.9 percent specificity
Interval 70.5 to 85.2
|
88.4 percent specificity
Interval 81.6 to 95.1
|
73.6 percent specificity
Interval 67.6 to 79.6
|
|
Specificity of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR LVEF
|
95.0 percent specificity
Interval 91.2 to 98.9
|
90.5 percent specificity
Interval 84.2 to 96.8
|
86.3 percent specificity
Interval 81.6 to 91.0
|
|
Specificity of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular end-diastolic indexed (LVEDVI)
|
75.2 percent specificity
Interval 67.5 to 82.9
|
52.4 percent specificity
Interval 41.7 to 63.1
|
61.5 percent specificity
Interval 54.8 to 68.1
|
|
Specificity of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular end-systolic volume index (LVESVI)
|
99.2 percent specificity
Interval 97.6 to 100.0
|
69.0 percent specificity
Interval 59.2 to 78.9
|
76.6 percent specificity
Interval 70.8 to 82.4
|
|
Specificity of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular stroke volume index (LVSVI)
|
92.6 percent specificity
Interval 87.9 to 97.2
|
42.9 percent specificity
Interval 32.3 to 55.4
|
90.7 percent specificity
Interval 86.8 to 94.7
|
PRIMARY outcome
Timeframe: Through 36 monthsAccuracy is defined as (true positives + true negatives) divided by the total number of cases * Myocardial dysfunction was defined as the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \> 10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL. * In patients with LVEF \< 53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \> 10% or a HF hospitalization. * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \>199 pg/mL.
Outcome measures
| Measure |
MyoStrain® Unblinded Treatment Arm
n=25 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group
* The unblinded treatment arm will enhance patient management by augmenting standard of care with serial MyoStrain® monitoring of the impact of cancer therapy on myocardial function.
* Higher Risk unblinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
MyoStrain® Blinded Control Arm
n=18 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk group
* The blinded control arm will provide investigators with LVEF and LVEDV/LVESV measurements, which are clinical, in conjunction with standard of care
* Higher Risk blinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
Combined MyoStrain® Control Arm and Treatment Arm
n=43 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group.
* After meeting eligibility criteria, patients will be further randomized to an unblinded arm (MyoStrain® measured and available to the treatment team) and a blinded arm (MyoStrain® measured but not available to the treatment team). This randomization will aid in an exploratory aim of testing the feasibility of MyoStrain® to guide cardioprotective therapy in the unblinded vs blinded arms. However, as all patients will have MyoStrain® measured, all patients (both treatment arms) will be combined for testing the primary outcome measure.
|
|---|---|---|---|
|
Accuracy of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
MyoStrain®
|
78.6 percent accuracy
Interval 71.8 to 85.4
|
85.1 percent accuracy
Interval 78.2 to 92.1
|
75.1 percent accuracy
Interval 69.6 to 80.6
|
|
Accuracy of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR LVEF
|
87.1 percent accuracy
Interval 81.5 to 92.6
|
84.8 percent accuracy
Interval 77.8 to 91.9
|
80.3 percent accuracy
Interval 75.2 to 85.3
|
|
Accuracy of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular end-diastolic indexed (LVEDVI)
|
71.2 percent accuracy
Interval 63.7 to 78.7
|
54.5 percent accuracy
Interval 44.7 to 64.4
|
59.7 percent accuracy
Interval 53.4 to 65.9
|
|
Accuracy of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular end-systolic volume index (LVESVI)
|
89.2 percent accuracy
Interval 84.1 to 94.4
|
68.7 percent accuracy
Interval 59.6 to 77.8
|
72.3 percent accuracy
Interval 66.6 to 78.0
|
|
Accuracy of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment
CMR left ventricular stroke volume index (LVSVI)
|
84.9 percent accuracy
Interval 78.9 to 90.8
|
50.5 percent accuracy
Interval 40.7 to 60.4
|
82.8 percent accuracy
Interval 78.0 to 87.6
|
PRIMARY outcome
Timeframe: Through 36 monthsPopulation: Events were excluded if there was an earlier event in the same patient closer in time to the MRI scan (6 events). Events were also excluded if they were \> 6 months from the last MRI scan (1 event).
Myocardial dysfunction is the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \>10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL * In patients with LVEF \<53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \>10% or a HF hospitalization * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \>199 pg/mL
Outcome measures
| Measure |
MyoStrain® Unblinded Treatment Arm
n=8 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group
* The unblinded treatment arm will enhance patient management by augmenting standard of care with serial MyoStrain® monitoring of the impact of cancer therapy on myocardial function.
* Higher Risk unblinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
MyoStrain® Blinded Control Arm
n=10 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk group
* The blinded control arm will provide investigators with LVEF and LVEDV/LVESV measurements, which are clinical, in conjunction with standard of care
* Higher Risk blinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
Combined MyoStrain® Control Arm and Treatment Arm
n=18 Participants
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group.
* After meeting eligibility criteria, patients will be further randomized to an unblinded arm (MyoStrain® measured and available to the treatment team) and a blinded arm (MyoStrain® measured but not available to the treatment team). This randomization will aid in an exploratory aim of testing the feasibility of MyoStrain® to guide cardioprotective therapy in the unblinded vs blinded arms. However, as all patients will have MyoStrain® measured, all patients (both treatment arms) will be combined for testing the primary outcome measure.
|
|---|---|---|---|
|
Independent Effectiveness of MyoStrain® to Detect Cardiac Dysfunction Compared to Standard Cardiac Imaging Measures
Clinical events
|
7 myocardial dysfunction events
|
7 myocardial dysfunction events
|
14 myocardial dysfunction events
|
|
Independent Effectiveness of MyoStrain® to Detect Cardiac Dysfunction Compared to Standard Cardiac Imaging Measures
Subclinical events
|
10 myocardial dysfunction events
|
8 myocardial dysfunction events
|
18 myocardial dysfunction events
|
Adverse Events
MyoStrain® Unblinded Treatment Arm
Serious events: 0 serious events
Other events: 1 other events
Deaths: 4 deaths
MyoStrain® Blinded Control Arm
Serious events: 0 serious events
Other events: 1 other events
Deaths: 4 deaths
Non-randomized
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 |
MyoStrain® Unblinded Treatment Arm
n=25 participants at risk
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group
* The unblinded treatment arm will enhance patient management by augmenting standard of care with serial MyoStrain® monitoring of the impact of cancer therapy on myocardial function.
* Higher Risk unblinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
MyoStrain® Blinded Control Arm
n=18 participants at risk
* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk group
* The blinded control arm will provide investigators with LVEF and LVEDV/LVESV measurements, which are clinical, in conjunction with standard of care
* Higher Risk blinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit.
* In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.
|
Non-randomized
n=6 participants at risk
-Patients were enrolled but not randomized to either arm.
|
|---|---|---|---|
|
Psychiatric disorders
Anxiety
|
4.0%
1/25 • Adverse events and all-cause mortality will be tracked from time of consent to the last study visit (up to 36 months).
Only adverse events in relation to the study procedures will be documented and reported. These include adverse events occurring from the MRI scanner, SENC MyoStrain® Testing Software, or breach of confidentiality.
|
5.6%
1/18 • Adverse events and all-cause mortality will be tracked from time of consent to the last study visit (up to 36 months).
Only adverse events in relation to the study procedures will be documented and reported. These include adverse events occurring from the MRI scanner, SENC MyoStrain® Testing Software, or breach of confidentiality.
|
0.00%
0/6 • Adverse events and all-cause mortality will be tracked from time of consent to the last study visit (up to 36 months).
Only adverse events in relation to the study procedures will be documented and reported. These include adverse events occurring from the MRI scanner, SENC MyoStrain® Testing Software, or breach of confidentiality.
|
Additional Information
Dr. Joshua Mitchell
Washington University School of Medicine
Phone: 314-362-1291
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place