Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol - Full Text View

Sponsor:	University of Maryland
Information provided by (Responsible Party):	Steve Gottlieb, University of Maryland
ClinicalTrials.gov Identifier:	NCT00806390

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	Intervention	Phase
Cardiomyopathy	Drug: Metoprolol	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	GCC0766: Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol

Resource links provided by NLM:

MedlinePlus related topics: Cardiomyopathy

Drug Information available for: Metoprolol Metoprolol Tartrate Metoprolol succinate Metoprolol fumarate Trastuzumab

U.S. FDA Resources

Further study details as provided by University of Maryland:

Primary Outcome Measures:

Ejection Fraction by MUGA [ Time Frame: Pre and post anthracycline treatment ] [ Designated as safety issue: No ]

Estimated Enrollment:	188
Study Start Date:	July 2008
Estimated Study Completion Date:	June 2012
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Metoprolol Receiving metoprolol	Drug: Metoprolol Metroprolol tartrate titrated up
No Intervention: Control Not receiving metoprolol

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.
Age > 18 years
Ability to understand and willingness to sign a written informed consent document.
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:

Patients who have established dilated or restrictive cardiomyopathy with EF < 40 %.
Patients with severe mitral or aortic valve disease (valve area <1cm squared).
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
Patients who have untreated thyroid function disorder.
Pregnant and nursing women are excluded from this study because of potential risk for adverse events to the fetus.
Patients with any impediment to swallowing tablets would be excluded.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00806390

Contacts

Contact: Stephen S Gottlieb, MD

4103288788

sgottlie@medicine.umaryland.edu

Locations

United States, Maryland
University of Maryland	Recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Stephen S Gottlieb, MD
Sub-Investigator: Jennifer Brown, MD

Sponsors and Collaborators

University of Maryland

Investigators

Principal Investigator:

Stephen S Gottlieb, MD

University of Maryland

More Information

No publications provided

Responsible Party:	Steve Gottlieb, Professor, University of Maryland
ClinicalTrials.gov Identifier:	NCT00806390 History of Changes
Other Study ID Numbers:	HP-00040965
Study First Received:	December 8, 2008
Last Updated:	October 27, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Maryland:

ejection fraction
anthracyclines
beta-adrenergic blockade
Patients receiving anthracyclines

Additional relevant MeSH terms:

Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Metoprolol
Metoprolol succinate
Trastuzumab
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents

Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 09, 2012