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 : Not yet recruiting
First Posted : June 14, 2017
Last Update Posted : June 16, 2017
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|
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|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Estimated Study Start Date :||July 2017|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||January 2020|
Placebo Comparator: Placebos
Other Name: Placebo
Atorvastatin 40mg od
Other Name: Statin
- 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.
- 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
- 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%
- 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
- 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
- BNP [ Time Frame: From start of anthracycline therapy to within 4 weeks of cancer therapy completion ]Maximal increase in BNP
- Myocardial strain [ Time Frame: From start of anthracycline therapy to within 4 weeks of cancer therapy completion ]Maximal change in myocardial strain
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03186404
|Contact: Yobiga Thevakumaran||416-340-4800 ext firstname.lastname@example.org|
|Toronto General Hospital|
|Toronto, Ontario, Canada, M5G 2N2|
|Principal Investigator:||Paaladinesh Thavendiranathan||University Health Network, Toronto|
|Principal Investigator:||Eitan Amir||University Health Network, Toronto|