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Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01988571
Recruitment Status : Completed
First Posted : November 20, 2013
Results First Posted : January 4, 2022
Last Update Posted : January 4, 2022
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:
The purpose of this research study is to see if Atorvastatin (Lipitor) 40 mg by mouth daily decreases the chance of developing heart problems in individuals receiving adjuvant anthracycline-based chemotherapy for breast cancer of lymphoma.

Condition or disease Intervention/treatment Phase
Breast Cancer Lymphoma Drug: Atorvastatin Drug: Placebo Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

Specific Aim 1:

To determine if Atorvastatin(Lipitor) administration preserves left ventricular ejection fraction (LVEF) 24 months after initiation of Anthracycline-based adjuvant therapy for adjuvant treatment of breast cancer or lymphoma.

Specific Aim 2:

To determine if baseline to 6-month differences in LVEF predict baseline to 24-month differences in LVEF after Anthracycline-based adjuvant therapy and concomitant atorvastatin therapy.

To achieve these aims, we will perform a double-blind, placebo-controlled, randomized clinical trial of 0 or 40 mg of atorvastatin/day in 278 individuals scheduled to receive Anthracycline-based chemotherapy for treatment of Stage I-III breast cancer or lymphoma Stage I-IV with a projected > 2 year life expectancy. We will use innovative noninvasive magnetic resonance imaging (MRI) procedures to accurately measure LVEF. In addition, we will measure left ventricle (LV) volumes, myocardial strain, fibrosis, aortic pulse wave velocity (PWV) and wall thickness, all factors that can influence LVEF by altering LV pre-load, after-load, and contractility.19,20 Advanced serum biomarkers will be measured that assess for the presence of oxidative/nitrosative stress, systemic inflammation and circulating neurohormones that also may influence LVEF.

This study will test a new clinical paradigm to manage breast cancer: primary prevention of Anthracycline-based adjuvant therapy-related LV dysfunction using pre-treatment with low-cost statins. In addition, this trial will be the first systematic collection of data regarding the mechanism(s) and time course by which LV dysfunction and subsequent chronic heart failure (CHF) evolve in individuals given Anthracycline-based chemotherapy for breast cancer or lymphoma. These data will be useful to physicians trying to determine the optimal cardiac protection strategies when administering adjuvant chemotherapeutic regimens to their breast cancer or lymphoma patients. The objective of this research is to use inexpensive medications to preserve cardiovascular (CV) health and thereby improve overall survival in the growing number of breast cancer and lymphoma patients.

SECONDARY OBJECTIVES

Specific Aim 1:

To document the effect of Atorvastatin (Lipitor) on cognitive function using a battery of neurocognitive tests (HVLT, Rey-osterrieth Figure, controlled oral word association test (COWA), Trail-making Parts A and B, Digit Span and Grooved Pegboard) in breast cancer and lymphoma patients receiving an anthracycline.

Specific Aim 2:

To document the effect of Atorvastatin(Lipitor) on self-reported quality of life using validated questionnaires (PROMIS including: General form, Cog Concerns, Cog Abilities, Fatigue, Pain intensity and interference, Sleep Disturbance, Physical Functioning and Social Functioning) in breast cancer and lymphoma patients receiving an anthracycline.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 279 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)
Actual Study Start Date : February 1, 2014
Actual Primary Completion Date : September 24, 2020
Actual Study Completion Date : September 24, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm 1 - Atorvastatin
One 40 mg Atorvastatin tablet each morning by mouth for 24 months
Drug: Atorvastatin
40 mg tablet taken by mouth each morning for 24 months.
Other Name: Lipitor

Placebo Comparator: Arm 2 - Placebo
One placebo tablet each morning by mouth for 24 months.
Drug: Atorvastatin
40 mg tablet taken by mouth each morning for 24 months.
Other Name: Lipitor

Drug: Placebo
One placebo tablet taken each morning orally for 24 months.
Other Name: sugar pill




Primary Outcome Measures :
  1. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 24 months ]
    24 month estimated values of clinical measurements obtained from Cardiac MRI left ventricular ejection fraction by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.


Secondary Outcome Measures :
  1. End Diastolic Volume [ Time Frame: 24 months ]
    24 month estimated values of clinical measurements obtained from Cardiac MRI End Diastolic Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

  2. End Systolic Volume [ Time Frame: 24 months ]
    24 month estimated values of clinical measurements obtained from Cardiac MRI End Systolic Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

  3. Stroke Volume [ Time Frame: 24 months ]
    24 month estimated values of clinical measurements obtained from Cardiac MRI Stroke Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

  4. Left Ventricular (LV) Mass [ Time Frame: 24 months ]
    24 month estimated values of clinical measurements obtained from Cardiac MRI left ventricular mass by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

  5. Pulse Wave Velocity [ Time Frame: 24 months ]
    24 month estimated values of clinical measurements obtained from Cardiac MRI pulse wave velocity by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

  6. Hopkins Verbal Learning Test (HVLT) Total Recall [ Time Frame: 24 months ]
    24 month estimated values Hopkins Verbal Learning test (HVLT) total recall by group. Linear model adjusts for baseline value and group assignment. No missing imputation performed. Ranges from 0 to 36 and higher numbers reflect better recall.

  7. Controlled Oral Word Association (COWA) [ Time Frame: 24 months ]
    24 month estimated values Controlled Oral Word Association (COWA) by group. Linear model adjusts for baseline value and group assignment. No missing imputation performed. The COWA uses the three letter set of C, F, and L to assess phonemic fluency. Individuals are given 1 min to name as many words as possible beginning with one of the letters. The procedure is then repeated for the remaining two letters. Ranges from 0 to the total number of correct words that begin with one of the letters in the set. There is no ceiling of a maximum score. Higher numbers reflect better verbal fluency.

  8. Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Applied Cognition - General Concerns - Short Form 4a [ Time Frame: 24 months ]
    Patient reported quality of life outcomes obtained from patient-reported outcomes measurement (PROMIS) questionnaire - Applied Cognition - General Concerns - Short Form 4a . Scores range from 4-20 and then adjusted by t-scores ranging from 30.1-63.8. Higher scores reflect better cognition. Linear models include baseline assessment and group and multiple imputation was utilized.

  9. Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Fatigue Short Form 41 [ Time Frame: 24 months ]
    Patient reported quality of life outcomes obtained from patient-reported outcomes measurement (PROMIS) questionnaire - Fatigue Short Form 41. Scores range from 4-20 and then adjusted by t-scores ranging from 33.7-75.8. Higher scores reflect worse fatigue. Linear models include baseline assessment and group and multiple imputation was utilized.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Stage I-III breast cancer (including inflammatory and newly diagnosed recurrent breast cancer) or lymphoma Stage I-IV. (Patients should have a > 2 year life expectancy)
  • Scheduled to receive adjuvant chemotherapy with an Anthracycline (doxorubicin and epirubicin)
  • 21 years of age or older
  • LVEF > 50% (Most recent within the last 5 years)
  • Prior administration of anthracyclines is acceptable if therapy was completed > 6 months prior to study enrollment
  • Patients that are receiving or have received chemotherapy regimens are allowed
  • Able to hold breath for 10 seconds
  • Prior cancers allowed if no evidence of disease in last 5 years
  • Eastern Cooperative Oncology Group (ECOG) 0 or 1

Exclusion Criteria:

  • Prior use of lipid-lowering therapy within the last 6 months
  • Current postmenopausal hormone-replacement therapy
  • Uncontrolled hypertension (systolic blood pressure >190 mm Hg or diastolic blood pressure >100 mm Hg)
  • Scheduled to receive neoadjuvant chemotherapy with an anthracycline
  • No active liver disease allowed
  • Uncontrolled hypothyroidism
  • Recent history (within past 3 years) of alcohol or drug abuse, inflammatory conditions such as lupus or inflammatory bowel disease, use of immunosuppressant agents, or another medical condition that might compromise safety or the successful completion of the study.
  • Patients with ferromagnetic cerebral aneurysm clips or other intraorbital/intracranial metal;pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices.
  • Unstable angina; significant ventricular arrhythmias (>20 premature ventricular complexes (PVCs)/min due to gating difficulty) atrial fibrillation with uncontrolled ventricular response; coronary artery disease; acute myocardial infarction within 28 days
  • Current use of Cytochrome P450 (CYP3A4) inhibitors. These include Clarithromycin, HIV protease inhibitors, Itraconazole, grapefruit juice, Cyclosporine, Rifampin or Digoxin
  • Current or history of hepatic dysfunction
  • Unable to provide informed consent
  • Claustrophobia
  • Planning to move within 24 months of trial enrollment
  • Pregnant or breast-feeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01988571


Locations
Show Show 51 study locations
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Gregory Hundley, MD Wake Forest University Health Sciences
  Study Documents (Full-Text)

Documents provided by Wake Forest University Health Sciences:
Informed Consent Form  [PDF] February 1, 2018

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT01988571    
Other Study ID Numbers: IRB00038639
U10CA081851 ( U.S. NIH Grant/Contract )
1R01HL118740-01 ( U.S. NIH Grant/Contract )
REBACCCWFU 98213 ( Other Identifier: NCI )
NCI-2013-01760 ( Registry Identifier: NCI CTRP )
First Posted: November 20, 2013    Key Record Dates
Results First Posted: January 4, 2022
Last Update Posted: January 4, 2022
Last Verified: December 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wake Forest University Health Sciences:
Stage I breast cancer
Stage II breast cancer
Stage III breast cancer
Stage I Lymphoma
Stage II Lymphoma
Stage III Lymphoma
Stage IV Lymphoma
Additional relevant MeSH terms:
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Lymphoma
Breast Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Breast Diseases
Skin Diseases
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors