Study of DITPA in Patients With Congestive Heart Failure

This study has been terminated.
(Study terminated for reasons unrelated to safety or efficacy.)
Sponsor:
Information provided by (Responsible Party):
Titan Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00103519
First received: February 9, 2005
Last updated: March 27, 2013
Last verified: November 2006
  Purpose

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.


Condition Intervention Phase
Heart Failure, Congestive
Drug: DITPA (3,5-diiodothyropropionic acid)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Titan Pharmaceuticals:

Primary Outcome Measures:
  • Safety and tolerability of DITPA

Secondary Outcome Measures:
  • Efficacy of DITPA

Enrollment: 86
Study Start Date: December 2004
Study Completion Date: December 2006
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DITPA 180 mg/day
DITPA 180 mg/day BID
Drug: DITPA (3,5-diiodothyropropionic acid)
Experimental: DITPA 360 mg/day
DITPA 360 mg/day BID
Drug: DITPA (3,5-diiodothyropropionic acid)
Placebo Comparator: Placebo
Placebo BID
Drug: Placebo
Placebo

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103519

  Hide Study Locations
Locations
United States, Alabama
The Heart Center
Huntsville, Alabama, United States, 35806
United States, Arizona
Cardiac Solutions
Peoria, Arizona, United States, 85381
University of Arizona Sarver Heart Center
Tucson, Arizona, United States, 85724
United States, California
University of Southern California
Los Angeles, California, United States, 90033
UCLA Medical Center
Los Angeles, California, United States, 90095
University of California, San Francisco
San Francisco, California, United States, 94143
Cardiovascular Consultants Medical Group
Walnut Creek, California, United States, 94598
United States, Georgia
Saint Joseph's Research Institute
Atlanta, Georgia, United States, 30342
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Louisiana
Louisiana State University Health Science Center
Shreveport, Louisiana, United States, 71103
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Columbia University New York Presbyterian Hospital
New York, New York, United States, 10032
United States, Ohio
Cincinnati VA Medical Center
Cincinnati, Ohio, United States, 45220
Clevaland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Oklahoma
Oklahoma Foundation for Cardiovascular Research
Oklahoma City, Oklahoma, United States, 73120
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Baylor University Medical Center Heart Place
Dallas, Texas, United States, 75226
United States, Virginia
The University of Virginia Health System
Charlottesville, Virginia, United States, 22908
United States, Wisconsin
William S. Middleton Memorial Veterans Hospital
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
Titan Pharmaceuticals
Investigators
Study Chair: Milton Packer, MD UT Southwestern Medical Center
  More Information

No publications provided

Responsible Party: Titan Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00103519     History of Changes
Other Study ID Numbers: DIT-803
Study First Received: February 9, 2005
Last Updated: March 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Titan Pharmaceuticals:
Heart Failure, DITPA

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 26, 2014