Heart Failure
Conditions
Keywords
Cancer Treatment Related to Heart Failure
Brief summary
This research study will test whether atorvastatin, a drug commonly prescribed for reducing cholesterol levels, can protect the heart during chemotherapy with doxorubicin. Atorvastatin is from a family of medications that are commonly called statins
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of a drug and determine whether the investigational drug works in treating a specific disease. Investigational means that the drug is being studied. The chemotherapy drug that the participant have been scheduled to be treated with, Doxorubicin, has been associated with the development of heart failure in some patients. This research study is testing whether Atorvastatin can protect the hearts of patients being treated with Doxorubicin and can reduce cardiac injury and the risk of heart failure. Atorvastatin is not approved by the FDA (the U.S. Food and Drug Administration) for use to reduce the cardiac injury after Doxorubicin. Atorvastatin is approved by the FDA for lowering cholesterol and for reducing the risk of heart attack and stroke. The heart is a muscle that pumps blood and Atorvastatin may protect the heart by preserving cardiac muscle function. The investigators will test whether atorvastatin protects the heart using a combination of imaging tests on the participants heart, blood tests, and stress testing. The imaging tests will involve an echocardiogram (an echo) and cardiac magnetic resonance (CMR), a type of magnetic resonance imaging (MRI) scan.
Interventions
DRUGPlacebo
A pill taken once a day
DRUGAtorvastatin
A pill taken once a day
Sponsors
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \> 18 years of age * All patients with newly diagnosed NHL and HL * Scheduled to receive anthracycline-based therapy
Exclusion criteria
* Statin use or Statin use is indicated based on guidelines * Pregnancy or breastfeeding * Unable to provide informed consent * Unexplained persistent elevation of transaminases (\>3 times upper limits of normal) * Concomitant use of cyclosporine * Renal failure: estimated glomerular filtration \<45 mL/min/1.73 m2 * Contraindication to a CMR (metallic object, severe claustrophobia, pacemaker, vascular clip * LVEF of \<50% at baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Individuals in Each Group With a Significant Decline in the LVEF. | 12 months | To determine if the administration of statins is associated with a lower percentage of individuals who experience a significant decline in the LVEF at 12 months. The primary outcome was the percentage of participants with an absolute decline in left ventricular ejection fraction (LVEF) of\>10% from prior to chemotherapy to a final value of \<55% over 12 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants in Each Group With New Onset Heart Failure. | 2 years | To determine whether statins reduce the percentage of participants in each group with new onset heart failure after anthracyclines. |
| Myocardial Extracellular Volume by Cardiac MRI. | 1 Year | The myocardial extracellular volume (ECV) is the proportion of the myocardium that is estimated to be of extracellular space. Myocardium consists of intracellular space and extracellular space. This measure is an imaging estimate of the extracellular space. The extracellular space can be expanded in diseases where myocardial fibrosis is increased. Thus, this measure is often used as an estimate for the proportion of fibrosis in the heart. It can be expressed as a percentage. Here, based on published literature, we used a cut off of a 3% increase in the ECV from baseline to follow-up as a meaningful increase and compared the propositions of persons with that 3% increase in each group. We are comparing the proportion of persons in each group with a 3% or greater increase in the ECV. |
| Global Longitudinal Strain (GLS) | 1 year | GLS is a sensitive measure of cardiac systolic function. Anthracyclines can be associated with impaired global longitudinal strain (GLS). Whether atorvastatin protects against a decline in LV GLS is unknown. GLS is expressed as a percentage. A ≥15% relative decrease in LV GLS was used as a cut off for a significant decrease in GLS based on published data. The Proportions of participants with a relative reduction of ≥15% in LV GLS were evaluated in each group. |
Countries
Canada, United States
Participant flow
Pre-assignment details
1:1 randomization
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo group | 150 |
| Atorvastatin Atorvastatin group | 150 |
| Total | 300 |
Baseline characteristics
| Characteristic | Placebo | Atorvastatin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 20 Participants | 40 Participants |
| Age, Categorical Between 18 and 65 years | 130 Participants | 130 Participants | 260 Participants |
| Age, Continuous | 49 years STANDARD_DEVIATION 16 | 50 years STANDARD_DEVIATION 17 | 50 years STANDARD_DEVIATION 16 |
| LVEF | 62.5 % STANDARD_DEVIATION 4.9 | 63 % STANDARD_DEVIATION 4.5 | 63 % STANDARD_DEVIATION 4.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) White | 131 Participants | 135 Participants | 266 Participants |
| Region of Enrollment Canada | 10 participants | 10 participants | 20 participants |
| Region of Enrollment United States | 140 participants | 140 participants | 280 participants |
| Sex: Female, Male Female | 74 Participants | 68 Participants | 142 Participants |
| Sex: Female, Male Male | 76 Participants | 82 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 150 | 4 / 150 |
| other Total, other adverse events | 21 / 150 | 28 / 150 |
| serious Total, serious adverse events | 0 / 150 | 0 / 150 |
Outcome results
Primary
The Percentage of Individuals in Each Group With a Significant Decline in the LVEF.
To determine if the administration of statins is associated with a lower percentage of individuals who experience a significant decline in the LVEF at 12 months. The primary outcome was the percentage of participants with an absolute decline in left ventricular ejection fraction (LVEF) of\>10% from prior to chemotherapy to a final value of \<55% over 12 months.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | The Percentage of Individuals in Each Group With a Significant Decline in the LVEF. | 22 Participants |
| Atorvastatin | The Percentage of Individuals in Each Group With a Significant Decline in the LVEF. | 9 Participants |
Secondary
Global Longitudinal Strain (GLS)
GLS is a sensitive measure of cardiac systolic function. Anthracyclines can be associated with impaired global longitudinal strain (GLS). Whether atorvastatin protects against a decline in LV GLS is unknown. GLS is expressed as a percentage. A ≥15% relative decrease in LV GLS was used as a cut off for a significant decrease in GLS based on published data. The Proportions of participants with a relative reduction of ≥15% in LV GLS were evaluated in each group.
Time frame: 1 year
Population: The number of persons in each group with high quality imaging data where the variable could be analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Global Longitudinal Strain (GLS) | 28 Participants |
| Atorvastatin | Global Longitudinal Strain (GLS) | 19 Participants |
Secondary
Myocardial Extracellular Volume by Cardiac MRI.
The myocardial extracellular volume (ECV) is the proportion of the myocardium that is estimated to be of extracellular space. Myocardium consists of intracellular space and extracellular space. This measure is an imaging estimate of the extracellular space. The extracellular space can be expanded in diseases where myocardial fibrosis is increased. Thus, this measure is often used as an estimate for the proportion of fibrosis in the heart. It can be expressed as a percentage. Here, based on published literature, we used a cut off of a 3% increase in the ECV from baseline to follow-up as a meaningful increase and compared the propositions of persons with that 3% increase in each group. We are comparing the proportion of persons in each group with a 3% or greater increase in the ECV.
Time frame: 1 Year
Population: Persons with available and high quality MRI data where the variable could be measured.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Myocardial Extracellular Volume by Cardiac MRI. | 29 Participants |
| Atorvastatin | Myocardial Extracellular Volume by Cardiac MRI. | 8 Participants |
Secondary
The Percentage of Participants in Each Group With New Onset Heart Failure.
To determine whether statins reduce the percentage of participants in each group with new onset heart failure after anthracyclines.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | The Percentage of Participants in Each Group With New Onset Heart Failure. | 6 Participants |
| Atorvastatin | The Percentage of Participants in Each Group With New Onset Heart Failure. | 3 Participants |