Study of DITPA in Patients With Congestive Heart Failure
Information source: Titan Pharmaceuticals
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Heart Failure, Congestive
Intervention: DITPA (3,5-diiodothyropropionic acid) (Drug); Placebo (Drug)
Phase: Phase 2
Status: Terminated
Sponsored by: Titan Pharmaceuticals Official(s) and/or principal investigator(s): Milton Packer, MD, Study Chair, Affiliation: UT Southwestern Medical Center
Summary
This study will assess the safety and efficacy of DITPA relative to placebo in patients with
New York Heart Association (NYHA) class III or IV congestive heart failure (CHF) who have
low serum T3. DITPA is an investigational agent.
Clinical Details
Official title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of DITPA in Patients With NYHA Class III and IV Congestive Heart Failure Who Have Low Serum T3 Levels
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Safety and tolerability of DITPA
Secondary outcome: Efficacy of DITPA
Detailed description:
Rationale: Congestive heart failure (CHF) is a major public health problem associated with
significant morbidity and mortality in patients with New York Heart Association (NYHA) class
III or IV disease. Multiple studies have identified a particularly high-risk group of
patients who have reduced thyroid hormone activity, specifically, low serum triiodothyronine
(T3) levels. This group represents approximately 30% of patients with NYHA class III or IV
disease and has significantly higher mortality rates than those with normal T3.
DITPA (3,5-diiodothyropropionic acid) is an analogue of naturally occurring thyroid hormone
(T3) that has been specifically designed to improve cardiac performance with a lower
potential for tachycardia in CHF patients. Although structurally similar to T3, DITPA has a
propionic acid side chain and lacks an iodine at the 3' position of the outer phenolic ring.
While DITPA binds to the same thyroid hormone receptors as T3, binding affinities are
significantly less, suggesting partial agonistic actions. Preclinical studies with DITPA
have supported a rationale for its use in patients with CHF.
Primary objective: To assess the safety and tolerability of DITPA in patients with NYHA
class III/IV CHF and low serum T3.
Secondary Objective: To obtain preliminary evidence of the efficacy of DITPA in patients
with NYHA class III/IV CHF and low serum T3
Design: The multi-center, randomized, double-blind, placebo-controlled study is designed to
evaluate the safety and tolerability of DITPA in patients with NYHA class III or IV CHF who
have low levels of serum T3 with normal levels of thyroid stimulating hormone (TSH).
One hundred and fifty patients at approximately 35 centers in the U. S. will be randomized to
1 of 3 treatment groups in a 1: 1:1 ratio (i. e., 50 patients per treatment group):
- DITPA at 180 mg/day (90 mg twice a day [BID], orally)
- DITPA at 360 mg/day (180 mg BID, orally)
- Placebo BID, orally
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Greater than or equal to 18 years of age
- NYHA class III or IV CHF
- Females must not be pregnant or lactating. Females of childbearing potential and
males must use a reliable means of contraception
- Serum total T3 <= 95 ng/dL with normal levels of TSH
- On a regimen consisting of angiotensin-converting enzyme inhibitors and/or
angiotensin receptor antagonists, beta blockers, and diuretics for a minimum of 3
months prior to randomization
- Clinically stable for 2 weeks prior to randomization (defined as no change in
functional class by NYHA, no hospitalization or ER visit, and no intravenous
inotropic or vasodilator treatment for 2 weeks)
- An LVEF <= 40%, documented within 6 months prior to randomization, or > 6 months with
confirmation of LVEF by local echocardiographic measurements within 2 weeks prior to
randomization
- Able to give informed consent
Exclusion Criteria:
- New onset CHF (less than 3 months prior to randomization)
- Active myocarditis, hypertrophic cardiomyopathy, uncorrected primary valvular
disease, restrictive cardiomyopathy, uncorrected congenital heart disease, or
constrictive pericarditis
- Myocardial infarction, unstable ischemic heart disease, stroke, or coronary
revascularization procedure within 4 weeks prior to randomization; or an expectation
of a coronary revascularization procedure, cardiac transplant, or left ventricular
assist device placement being needed within 24 weeks after randomization
- History of sudden arrhythmic syncope or sustained ventricular arrhythmia, unless the
patient has an implantable cardioverter defibrillator (ICD) for at least 12 weeks
prior to randomization; history of clinically significant heart block, unless the
patient has had a pacemaker at least 12 weeks prior to randomization
- History of cardiac resynchronization therapy in the last 12 weeks prior to
randomization or expectation of cardiac resynchronization therapy or ventricular
mechanical assistance needed within 24 weeks after randomization
- History of cardiac transplant
- Heart rate < 50 beats per minute or > 130 beats per minute
- Systolic blood pressure <= 80 mm Hg
- Serum creatinine => 2. 5 mg/dL
- Treatment with intravenous vasodilators (including nesiritide) or inotropes within 2
weeks prior to randomization
- Receipt of any other investigational agent or device within 4 weeks prior to
randomization
- Diagnosis of other non-cardiac underlying medical conditions expected to impact their
mortality within 24 weeks after randomization
- Drug or alcohol dependence, or other conditions which may affect study compliance
- History of thyroid disorders of any form within 24 weeks prior to randomization
- Use of thyroid supplements (levothyroxine, liothyronine, etc.) or any preparation
containing thyromimetic agents within 24 weeks prior to randomization
- Supraventricular arrhythmia refractory to conventional treatment, as judged by the
investigators
Locations and Contacts
The Heart Center, Huntsville, Alabama 35806, United States
Cardiac Solutions, Peoria, Arizona 85381, United States
University of Arizona Sarver Heart Center, Tucson, Arizona 85724, United States
UCLA Medical Center, Los Angeles, California 90095, United States
University of Southern California, Los Angeles, California 90033, United States
University of California, San Francisco, San Francisco, California 94143, United States
Cardiovascular Consultants Medical Group, Walnut Creek, California 94598, United States
Saint Joseph's Research Institute, Atlanta, Georgia 30342, United States
Rush University Medical Center, Chicago, Illinois 60612, United States
University of Louisville, Louisville, Kentucky 40202, United States
Louisiana State University Health Science Center, Shreveport, Louisiana 71103, United States
Mayo Clinic, Rochester, Minnesota 55905, United States
Columbia University New York Presbyterian Hospital, New York, New York 10032, United States
Cincinnati VA Medical Center, Cincinnati, Ohio 45220, United States
Clevaland Clinic Foundation, Cleveland, Ohio 44195, United States
Oklahoma Foundation for Cardiovascular Research, Oklahoma City, Oklahoma 73120, United States
Oregon Health Sciences University, Portland, Oregon 97239, United States
Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, United States
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, United States
Baylor University Medical Center Heart Place, Dallas, Texas 75226, United States
The University of Virginia Health System, Charlottesville, Virginia 22908, United States
William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705, United States
Additional Information
Starting date: December 2004
Last updated: March 27, 2013
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