Primary Prevention of Anthracycline-induced Cardiotoxicity with L-Carnitine in patients with breast Cancer (PPACC): pilot study
| ISRCTN | ISRCTN32332192 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN32332192 |
| ClinicalTrials.gov number | NCT00247975 |
| Secondary identifying numbers | MCT-78520 |
- Submission date
- 02/04/2007
- Registration date
- 02/04/2007
- Last edited
- 12/02/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Benjamin Chow
Scientific
Scientific
University of Ottawa Heart Institute
40 Ruskin Street
Ottawa
Ontario
K1Y 4W7
Canada
| Phone | +1 613 761 4044 |
|---|---|
| bchow@ottawaheart.ca |
Study information
| Study design | One centre, two arm, double blind, randomised, parallel group, placebo controlled trial, with study participant, study investigator, caregiver, outcome assessor and data-analyst blinding |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | Primary Prevention of Anthracycline-induced Cardiotoxicity with L-Carnitine in patients with breast Cancer (PPACC): pilot study |
| Study acronym | PPACC |
| Study objectives | Primary hypothesis: Compared to placebo, L-carnitine will reduce the cytotoxic effects of epirubicin on Left Ventricular Ejection Fraction (LVEF). Secondary hypothesis: Compared to placebo, patients treated with L-carnitine will have: 1. Smaller increases in LV end-systolic and end-diastolic volumes 2. Lower serum Troponin T (TnT) and Brain Natriuretic Peptide (BNP) levels 3. A reduced incidence of "anthracycline-induced cardiotoxicity" 4. Higher serum L-carnitine levels 5. Similar occurrence of adverse events (breast cancer response, seizures, etc.,) We will also test the hypothesis that TnT, BNP, serum L-carnitine levels correlate with changes in LVEF, end systolic volume, and end diastolic volume. |
| Ethics approval(s) | Approval received from the Human Research Ethics Board of University of Ottawa Heart Institute (Canada) on the 7th October 2005 (ref: UOHI 2006-124). |
| Health condition(s) or problem(s) studied | Breast Cancer |
| Intervention | Experimental group: L-Carnitine therapy plus chemotherapy (FEC-100): Oral L-carnitine (3 grams daily) for three days prior to chemotherapy, 1 gram of intravenous L-carnitine (5 cc over five minutes, prior to chemotherapy) on the day of chemotherapy and oral L-carnitine (3 grams daily) for three days after chemotherapy. Control group: placebo (matching L-Carnitine therapy) plus chemotherapy (FEC-100): Oral placebo for three days prior to chemotherapy, intravenous placebo (5 cc over five minutes, prior to chemotherapy) on the day of chemotherapy and oral placebo for three days after chemotherapy. Contact for public queries: Jason King University of Ottawa Heart Institute 40 Ruskin Street Ottawa, Ontario Canada K1Y 4W7 Tel: +1 613 761 9703 Fax: +1 613 761 4596 Email: jking@ottawaheart.ca |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | L-Carnitine, 5-fluorouracil, epirubicin, and cyclophosphamide |
| Primary outcome measure | 1. Change in Ejection Fraction (EF) (measure by Radionuclide Angiocardiography [RNA]) at one year, compared to the patient's own baseline. LVEF is used clinically to assess patients' eligibility for continued chemotherapy. |
| Secondary outcome measures | 1. LV end-systolic and end-diastolic volumes (RNA) 2. LV diastolic dysfunction (Echocardiography [ECHO]) 3. Serum TnT and BNP measured with each cycle of chemotherapy (immediately prior to and three days after chemotherapy) 4. Composite outcome of: cardiac death, clinical congestive heart failure, reduction in EF requiring termination of anthracycline therapy (LVEF reduction greater than or equal to 10% and LVEF less than 50%), dexrazoxane use or "anthracycline-induced cardiotoxicity" 5. Adverse events (e.g. chemotherapy efficacy, seizures, nausea, diarrhoea) A secondary analysis of correlation of serum biomarkers (serum L-Carnitine levels, serum TnT, BNP) with surrogate markers of cardiotoxicity (LVEF, LV volumes and diastolic dysfunction) will also be performed. |
| Overall study start date | 01/11/2005 |
| Completion date | 31/10/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Lower age limit | 18 Years |
| Sex | Not Specified |
| Target number of participants | 128 (Amended to 144 as of 20/04/2007) |
| Key inclusion criteria | 1. Breast cancer patients (stages I, II, III) eligible for adjuvant epirubicin chemotherapy (5-Fluorouracil, Epirubicin, and Cyclophosphamide [FEC]-100) 2. Eastern Cooperative Oncology Group (ECOG) performance status equals zero to two 3. Informed consent Amended as of 20/04/2007: 1. Women, aged greater than or equal to 18 years 2. Breast cancer patients (stages I, II, III) eligible for adjuvant epirubicin chemotherapy (FEC100) 3. HER2 negative breast cancer by immunohistochemistry (IHC3+) and/or fluorescent in-situ hybridization 4. Eastern Cooperative Oncology Group (ECOG) performance status equal to zero to two 5. Ability to understand and the willingness to sign a written informed consent document 6. Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately |
| Key exclusion criteria | 1. Resting LVEF less than 50% 2. Previous anthracycline therapy or contraindication to anthracycline 3. Contraindication to L-carnitine therapy 4. Dexrazoxane therapy at the time of enrolment 5. Participation in another randomised clinical trial 6. Significant cardiac disease (previous myocardial infarction, congestive heart failure, haemodynamically significant valvular heart disease) 7. Medication that may affect LV function or symptoms of heart failure (beta-blockers, amiodarone, Angiotensin Converting Enzyme [ACE]-inhibitors, calcium channel blockers, digoxin) 8. Aged less than 18 years or inability to give informed consent 9. Evidence of metastatic breast cancer 10. Patients unable to participate in a study requiring long term follow up 11. Abnormal baseline: Complete blood count (Haemoglobin [Hb] less than 100 mg/L, Platelets [Plt] less than 100 x 10^9/L, White Blood Cells [WBC] less than 4 x 10^9/L), creatinine, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) or bilirubin greater than 1.5 times the upper limit of normal Amended as of 20/04/2007: 1. Resting LVEF less than 50% 2. Previous anthracycline therapy or contraindication to anthracycline 3. Contraindication to L-carnitine therapy 4. Dexrazoxane therapy at the time of enrollment 5. Participation in another randomised clinical trial 6. Significant cardiac disease (previous myocardial infarction, congestive heart failure, hemodynamically significant valvular heart disease) 7. Medication that may affect LV function or symptoms of heart failure (b-blockers, amiodarone, ACE-inhibitors, calcium channel blockers, digoxin) 8. Pregnant or lactating women 9. Evidence of metastatic breast cancer. 10. Patients unable to participate in a study requiring long term follow up 11. Abnormal baseline: Complete blood count (Hb less than 100 mg/L, Plt less than 100 x 10^9/L, WBC less than 4 x 10^9/L), Creatinine AST, ALT or Bilirubin greater than or equal to 1.5 the upper limit of normal |
| Date of first enrolment | 01/11/2005 |
| Date of final enrolment | 31/10/2008 |
Locations
Countries of recruitment
- Canada
Study participating centre
University of Ottawa Heart Institute
Ontario
K1Y 4W7
Canada
K1Y 4W7
Canada
Sponsor information
University of Ottawa Heart Institute (Institut de cardiologie de l'Université d'Ottawa) (Canada)
University/education
University/education
40 Ruskin Street
Ottawa
Ontario
K1Y 4W7
Canada
| Website | http://www.ottawaheart.ca/UOHI/ |
|---|---|
"ROR" |
https://ror.org/03c4mmv16 |
Funders
Funder type
Research organisation
Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca/ (ref: MCT-78520)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Editorial Notes
12/02/2019: No publications found, verifying study status with principal investigator.
