Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
Overview[ - collapse ][ - ]
| Purpose | The primary objective of this study is to investigate whether giving prophylactic metoprolol prior to and during anthracycline or trastuzumab therapy will decrease the incidence of anthracycline-induced cardiomyopathy. Patients are randomized to receive metoprolol or no treatment prior to anthracycline or trastuzumab treatment. The ejection fraction, as measured by nuclear ventriculography is measured before and after treatment. |
|---|---|
| Condition | Cardiomyopathy |
| Intervention | Drug: Metoprolol |
| Phase | Phase 4 |
| Sponsor | University of Maryland |
| Responsible Party | University of Maryland |
| ClinicalTrials.gov Identifier | NCT00806390 |
| First Received | December 8, 2008 |
| Last Updated | December 9, 2013 |
| Last verified | December 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | December 8, 2008 |
|---|---|
| Last Updated Date | December 9, 2013 |
| Start Date | July 2008 |
| Estimated Primary Completion Date | June 2012 |
| Current Primary Outcome Measures | Ejection Fraction by MUGA [Time Frame: Pre and post anthracycline treatment] [Designated as safety issue: No] |
| Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
| Brief Title | Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol |
|---|---|
| Official Title | GCC0766: Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol |
| Brief Summary | The primary objective of this study is to investigate whether giving prophylactic metoprolol prior to and during anthracycline or trastuzumab therapy will decrease the incidence of anthracycline-induced cardiomyopathy. Patients are randomized to receive metoprolol or no treatment prior to anthracycline or trastuzumab treatment. The ejection fraction, as measured by nuclear ventriculography is measured before and after treatment. |
| Detailed Description | This is a randomized, controlled exploration. Consent will be obtained from patients receiving care for cancer with anthracycline or trastuzumab at the University Of Maryland Greenebaum Cancer Center prior to initiation of anthracycline or trastuzumab treatment during the initial oncology visit. Patients will be evaluated in the initial consultation in the oncology clinic during which time consent will be obtained, and any patient with bradycardia (HR less than 50) or other contraindication will be excluded from the study. The patients will be randomly assigned to metoprolol vs. control groups during this initial visit. Individuals in the control group will not receive any study drug where as those in the metoprolol group will be given prophylactic metoprolol prior to initiation of anthracycline or trastuzumab treatment. Metoprolol tartrate will be provided to each patient randomized to the metoprolol group. Also at the time of the initial consultation, a baseline MUGA will be obtained for evaluation of left ventricular ejection fraction. Additionally, a post-treatment MUGA will be obtained after the final course of chemotherapy. Lastly, also at the initial visit, one vial of blood will be obtained from each patient to test for genetic polymorphisms, as described in the background section, which may contribute to the response to beta blockade in the prevention of anthracycline or trastuzumab induced cardiomyopathy. Each participant in the metoprolol group will be started on 25 mg of metoprolol tartrate twice a day prior to initiation of the anthracycline or trastuzumab. After one week, this dose will be increased to 50 mg twice daily, if tolerated. Prior to increasing the dose, the patients will be seen in the cardiology research clinic by the study doctor and evaluated for side effects. After another week the dose will again be increased to 100 mg twice daily. The dose can be decreased at any time if side effects occur such as bradycardia with HR less than 50 or hypotension with SBP less than 90. The beta blocker will be held for two days prior to the post-treatment MUGA so as not to acutely affect heart rate, as a decrease in heart rate would be expected to increase EF14. Abrupt cessation of metoprolol tartrate will not lead to withdrawal of beta-blockade. This study will end with the post-treatment MUGA. The primary end point of this study will be the change in EF before and after anthracycline or trastuzumab treatment. A pill diary will be maintained to document compliance of study medication. |
| Study Type | Interventional |
| Study Phase | Phase 4 |
| Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention |
| Condition | Cardiomyopathy |
| Intervention | Drug: Metoprolol Metroprolol tartrate titrated up |
| Study Arm (s) |
|
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Terminated |
|---|---|
| Estimated Enrollment | 17 |
| Estimated Completion Date | June 2012 |
| Estimated Primary Completion Date | June 2012 |
| Eligibility Criteria | Inclusion Criteria: 1. Patients must have confirmed malignancy for which standard regimens of anthracyclines or trastuzumab are being offered as treatment at the University of Maryland Greenebaum Cancer Center. Patients must either receive 4 cycles of anthracycline for a total dose of 240 mg/m2 or six cycles of TAC for a total dose of 300 mg/m2 or trastuzumab. 2. Age > 18 years 3. Ability to understand and willingness to sign a written informed consent document. 4. Women of childbearing potential may participate in this study only if they have a negative pregnancy test and agree not to become pregnant during the study. Woman of childbearing potential must use an effective method of birth control such as hormonal contraceptives (oral and implant) condoms, diaphragms, spermicidal foam or jelly, surgical (hysterectomy or tubal ligation) or intrauterine device. Exclusion Criteria: 1. Patients who have established dilated or restrictive cardiomyopathy with EF < 40 %. 2. Patients with severe mitral or aortic valve disease (valve area <1cm squared). 3. Patients who have any contraindication to metoprolol, in particular bradycardia with HR < 50, or severe reactive pulmonary disease such as asthma. Patients who take mibefradil or psychiatric drugs (such as phenothiazines including chlorpromazine and thioridazine) will also be excluded from the study as they have serious interactions with beta-blockers 4. Patients who have untreated thyroid function disorder. 5. Pregnant and nursing women are excluded from this study because of potential risk for adverse events to the fetus. 6. Patients with any impediment to swallowing tablets would be excluded. |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00806390 |
|---|---|
| Other Study ID Numbers | HP-00040965 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | University of Maryland |
| Study Sponsor | University of Maryland |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Stephen S Gottlieb, MD University of Maryland |
| Verification Date | December 2013 |
Locations[ + expand ][ + ]
| University of Maryland | Baltimore, Maryland, United States, 21201 |
|---|