ClinicalTrials.gov
ClinicalTrials.gov Menu

Statins for the Primary Prevention of Heart Failure in Patients Receiving Anthracycline Pilot Study (SPARE-HF)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03186404
Recruitment Status : Recruiting
First Posted : June 14, 2017
Last Update Posted : October 12, 2018
Sponsor:
Collaborators:
University Health Network, Toronto
Mount Sinai Hospital, Canada
St. Michael's Hospital, Toronto
Sunnybrook Health Sciences Centre
Scarborough General Hospital
Information provided by (Responsible Party):
Dinesh Thavendiranathan, University Health Network, Toronto

Brief Summary:

Anthracycline (AC) chemotherapy has substantially reduced the mortality rate from several common cancers globally. Unfortunately, AC treatment is associated with up to 19% risk of heart failure (HF). Current standard of care for preventing AC induced HF (AIHF) is cardiac surveillance followed by initiation of treatment once HF is diagnosed. With this approach 89% of patients fail to recover heart function and 46% will experience adverse cardiac events. Therefore there is a need for effective preventive therapy to reduce the risk of AIHF. Based on small human studies, animal studies, and our own pilot data, statins are an ideal class of drug for this purpose.

We will conduct a pilot double blinded, placebo controlled, randomized controlled trial to assess whether pre-treatment with statins before AC can prevent heart dysfunction. Eligible patients with cardiovascular risk factors scheduled to receive AC will be recruited. They will be randomized to statin therapy or placebo and followed until the end of cancer treatment. Primary outcome is the difference in cardiac MRI-determined left ventricular ejection fraction between pre-AC and end of treatment.


Condition or disease Intervention/treatment Phase
Cancer Heart Failure Cardiotoxicity Drug: Atorvastatin Drug: Placebos Phase 2

Detailed Description:

STUDY DESIGN: This is a double blind, placebo controlled randomized controlled trial (RCT). We will also use stratification to ensure that the proportion of patients with different malignancies is balanced between the study arms.

PATIENT RECRUITMENT: Patients will be recruited from respective oncology clinics at Princess Margaret Hospital, Mount Sinai Hospital, St. Michael's Hospital, Sunnybrook Health Sciences Centre and Scarborough General Hospital.

INTERVENTION: Patients will receive treatment with 40mg/day of atorvastatin or placebo started 2-10 days prior to the initiation of AC and continued for one month after completion of cancer treatment.

CARDIAC MRI (CMR): Studies will be performed on a 3.0T scanner (Siemens) and will include complete function and tissue characterization. CMR studies will be performed pre-therapy and after completion of AC. After de-identification and randomization, a research assistant blinded to all clinical data will perform all CMR analysis using commercially available software.

ECHOCARDIOGRAPHY: Routine echocardiography studies will be performed at the time of Cardiac MRI.

SERUM BIOMARKERS: Blood work will be obtained on the day of baseline imaging, immediately after each cycle of anthracycline, and on the day of post treatment imaging . At each time point samples of bio-banking will be collected. Blood sample collection will be done locally at the participant's respective site and transferred to University Health Network (UHN) biobank for future analysis or analysis of markers that are not available at all sites (e.g. high sensitivity troponin I and BNP).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized Double Blind Placebo Controlled Trial of Statins for the Primary pREvention of Heart Failure in Patients With Cancer Receiving Anthracycline Based Chemotherapy
Actual Study Start Date : May 10, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : March 2020


Arm Intervention/treatment
Placebo Comparator: Placebos
Placebos
Drug: Placebos
Placebo
Other Name: Placebo

Experimental: Statin
Atorvastatin 40mg
Drug: Atorvastatin
Atorvastatin 40mg od
Other Name: Statin




Primary Outcome Measures :
  1. Cardiac MRI measured LVEF within 4 weeks of anthracycline completion [ Time Frame: Within 4 weeks of cancer therapy completion ]
    Cardiac MRI LVEF at the end of treatment will be measured before cancer treatment and within 4 weeks after completion of anthracycline-based treatment. The pre-treatment measurement will facilitate a baseline adjusted comparison between placebo and statin treated groups.


Other Outcome Measures:
  1. Cardiac MRI measured LV end diastolic volume (LVEDV) and end systolic volume (LVESV) at the end of treatment [ Time Frame: Within 4 weeks of anthracycline completion ]
    these measures will be obtained at the same time as the LVEF measures with pre-treatment measurements facilitating a baseline adjusted comparison between placebo and statin treated groups

  2. The incidence of cardiotoxicity [ Time Frame: From start of anthracycline therapy to upto 4 weeks of anthracycline completion ]
    defined by LVEF fall >10% from pre-cancer treatment assessment to <53%

  3. Interruption of study drug due to side effects or permanent cessation of study drug or cancer treatment due to cardiac dysfunction [ Time Frame: From start of anthracycline therapy to upto 4 weeks of anthracycline completion ]
    as defined by reduction in drug dose or delay of cancer treatment by more than 1 week or permanent cessation

  4. Troponin I [ Time Frame: Maximal increase in Troponin I between pre-anthracycline therapy to within 4 weeks of anthracycline completion ]
    Maximal increase in troponin I

  5. BNP [ Time Frame: From start of anthracycline therapy to within 4 weeks of cancer therapy completion ]
    Maximal increase in BNP

  6. Myocardial strain [ Time Frame: From start of anthracycline therapy to within 4 weeks of cancer therapy completion ]
    Maximal change in myocardial strain

  7. MRI tissue characterization parameters [ Time Frame: Within 4 weeks of anthracycline completion ]
    Maximal change in myocardial tissue characterization parameters as measured by cardiac MRI from pre-anthracycline treatment to within 4 weeks of anthracycline completion



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with one of the following malignancies requiring anthracycline based chemotherapy with a curative intent: breast cancer; aggressive lymphomas; leukemia (acute myelogenous leukemia, acute lymphoblastic leukemia, mixed phenotype acute leukemia) or; sarcoma
  2. Patients with high cardiovascular risk defined as:

    I. ≥60 years and at least one of the following:

    i. Compromised cardiac function based on baseline LVEF <55% measured by echocardiography or MUGA or moderate left sided valvular heart disease (moderate mitral or aortic regurgitation or stenosis) ii. Planned cumulative doxorubicin dose equivalent 200mg/m² or more iii. Prior anthracycline therapy at any cumulative dose or prior chest/mediastinal radiation therapy iv. Any one of hypertension, smoking, obesity (BMI≥30), history of cardiomyopathy or heart failure but with recovered LVEF to ≥ 50%

    OR

    II. Age <60 years with one of the following:

    i. and at least 2 of the risk factors listed above (I i-iv) ii. type 2 diabetes with age <40 iii. type 1 diabetes duration <15 years

    OR

    III. High anthracycline dose defined as ≥250mg/m² of doxorubicin, ≥600mg/m² epirubicin, or other isoequivalent dose

  3. Living within geographic area conducive to repeated clinical and imaging follow-up

Exclusion Criteria:

  1. Participating in another clinical research study where randomization would be unacceptable
  2. Previous history of statin intolerance
  3. Already on statin therapy or known statin indicated condition:

    I. atherosclerosis i. myocardial infarction ii. acute coronary syndrome iii. stable angina iv. documented coronary disease by angiography (>10% stenosis) v. stroke vi. TIA vii. documented carotid disease viii. peripheral arterial disease ix. claudication and/or ABI <0.9

    II. abdominal aortic aneurysm (>3.0cm or previous aneurysm surgery)

    III. chronic kidney disease (>3 months duration and ACR >3.0mg/mmol or eGFR <60mL/min/1.73m²)

    IV. most diabetes including:

    i. ≥40 years of age ii. age ≥30 years and 15 years duration of type 1 diabetes iii. known microvascular diseae

  4. CK level >3x upper limit of normal
  5. Evidence of hepatic dysfunction (ALT level >2x upper limit of normal)
  6. On a drug that is a strong inhibitor of cytochrome P450 3A4 or may require such treatment during the treatment period (because atorvastatin is metabolized by this pathway)
  7. Significant valvular heart disease defined as severe stenotic or regurgitant lesions of any of the cardiac valves
  8. Life expectancy less than 12 months
  9. Contraindication to cardiac MRI (e.g. implanted pacemakers, ICDs, other implanted ferromagnetic objects unsafe for cardiac MRI or will result in significant artifact, eGFR <30)
  10. Creatinine >177umol/L
  11. Known history of uncontrolled hypothyroidism (TSH level >1.5x upper limit of normal)

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): NCT03186404


Contacts
Contact: Yobiga Thevakumaran 416-340-4800 ext 3472 yobiga.thevakumaran@uhn.ca

Locations
Canada, Ontario
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: Paaladinesh Thavendiranathan    416-340-5326      
Sponsors and Collaborators
Dinesh Thavendiranathan
University Health Network, Toronto
Mount Sinai Hospital, Canada
St. Michael's Hospital, Toronto
Sunnybrook Health Sciences Centre
Scarborough General Hospital
Investigators
Principal Investigator: Paaladinesh Thavendiranathan University Health Network, Toronto
Principal Investigator: Eitan Amir University Health Network, Toronto

Responsible Party: Dinesh Thavendiranathan, Cardiologist, Director Ted Rogers Program in Cardotoxicity Prevention, Assistant Professor of Medicine, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT03186404     History of Changes
Other Study ID Numbers: SPARE HF Pilot
First Posted: June 14, 2017    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Drug-Related Side Effects and Adverse Reactions
Heart Failure
Cardiotoxicity
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Chemically-Induced Disorders
Radiation Injuries
Wounds and Injuries
Atorvastatin Calcium
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Enzyme Inhibitors