Prevention of Anthracycline Induced Cardiomyopathy by Metoprolol
Information source: University of Maryland
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cardiomyopathy
Intervention: Metoprolol (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: University of Maryland Official(s) and/or principal investigator(s):
Stephen S Gottlieb, MD, Principal Investigator, Affiliation: University of Maryland
Overall contact:
Stephen S Gottlieb, MD, Phone: 4103288788, Email: sgottlie@medicine.umaryland.edu
Summary
The primary objective of this study is to investigate whether giving prophylactic metoprolol
prior to and during anthracycline therapy will decrease the incidence of
anthracycline-induced cardiomyopathy. Patients are randomized to receive metoprolol or no
treatment prior to anthracycline treatment. The ejection fraction, as measured by nuclear
ventriculography is measured before and after treatment.
Clinical Details
Official title: GCC0766: Prevention of Anthracycline Induced Cardiomyopathy by Metoprolol
Study design: Prevention, Randomized, Open Label, Single Group Assignment, Efficacy Study
Primary outcome: Ejection Fraction by MUGA
Detailed description:
This is a randomized, controlled exploration. Consent will be obtained from patients
receiving care for cancer with anthracycline regimen at the University Of Maryland
Greenebaum Cancer Center prior to initiation of anthracycline 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 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 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. 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 treatment. A
pill diary will be maintained to document compliance of study medication.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Patients must have confirmed malignancy for which one of two standard regimens of
anthracyclines 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.
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.
Locations and Contacts
Stephen S Gottlieb, MD, Phone: 4103288788, Email: sgottlie@medicine.umaryland.edu
University of Maryland, Baltimore, Maryland 21201, United States; Recruiting
Stephen S Gottlieb, MD, Principal Investigator
Jennifer Brown, MD, Sub-Investigator
Additional Information
Starting date: July 2008
Last updated: July 8, 2009
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