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Diabetes MellitusPhase 3NCT00521820

Safety Comparison of Pioglitazone and Glyburide in Type 2 Diabetes Subjects With Mild to Moderate Congestive Heart Failure

A Phase 3 study testing Pioglitazone and Glyburide in people with Diabetes Mellitus, run by Takeda.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to compare the safety of Pioglitazone, once daily (QD), to Glyburide in Type 2 Diabetes Subjects with Mild to Moderate Congestive Heart Failure Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetes Mellitus
What is being tested?
Pioglitazone and Glyburide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
518 participants
Where
No sites listed yet
Study dates
Jun 2000to Oct 2003
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Females of childbearing potential must be using appropriate birth during the entire duration of the study or must be surgically sterile.
  • Subjects with a clear diagnosis of type 2 diabetes mellitus using diagnostic criteria of the American Diabetes Association who have been taking a sulfonylurea and/or insulin for at least 30 days prior to Visit 1 or who have been withdrawn from metformin therapy, during the 30 days prior to Visit 1, due to congestive heart failure.
  • Subjects with a clinical diagnosis of congestive heart failure, New York Heart Association Class II or early Class III. Subjects should not previously have been in Class IV heart failure.
  • Diagnosis of left ventricular congestive heart failure as evidenced by a left ventricular ejection fraction less than 40% at screening based on an echocardiogram.
  • Subjects who have demonstrated the need for oral hypoglycemic agents and have participated in dietary counseling.
  • Glycosylated hemoglobin greater than 7.0% at screening.
  • Subjects on optimal therapy for congestive heart failure. Medication doses should be stable for at least two weeks prior to randomization.

Who cannot join

  • Naïve to antidiabetic therapy.
  • Within the past three months were treated with rosiglitazone, pioglitazone HCl, or troglitazone or those previously treated with rosiglitazone, pioglitazone HCl, or troglitazone but discontinued from therapy due to lack of efficacy or clinical or laboratory signs of intolerance.
  • Type 1 (insulin-dependent) diabetes mellitus or a history of ketoacidosis.
  • Has taken any other investigational drug during the 30 days prior to Visit 1 or who will receive such a drug during the timeframe of this study.
  • History of chronic alcoholism or drug abuse during the six months prior to the study.
  • Has had any of the following within three months prior to Visit 1: myocardial infarction, coronary angioplasty or bypass graft, unstable angina pectoris, transient ischemic attacks, or documented cerebrovascular accident that in the investigator's opinion would warrant exclusion from the study.
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  • Abdominal, thoracic, or vascular surgery during the three months prior to Visit 1 that in the investigator's opinion would warrant exclusion from the study.
  • Subjects with a planned surgical or catheterization intervention within the six months following Visit 1.
  • Subjects awaiting cardiac transplantation.
  • Intercurrent illness severe enough to require hospitalization during the three weeks prior to Visit 1.
  • Body mass index greater than 48 kg/m2 as calculated by [Weight (kg)/Height (m)2].
  • Anemia having a hemoglobin less than 10.5 g/dL for males and less than 10 g/dL for females.
  • Thyroid stimulating hormone greater than 3.5 mU/L or less than 0.3 mU/L. The thyroid stimulating hormone can be repeated at two months. The subject is eligible if the screening thyroid stimulating hormone is elevated, and the repeat value at two months is less than 3.5 mU/L.
  • Triglyceride level greater than 500 mg/dL.
  • Clinical evidence of active liver disease or alanine transaminase levels greater than 1.5 times the upper limit of normal.
  • Serum creatinine greater than 2.0 mg/dL for males and greater than 1.8 mg/dL for females or urinalysis protein (albumin) excretion greater than 2 plus on Combistix or equivalent (if elevated, may be re-screened in one month).
  • Unstable coronary syndromes which in the opinion of the investigator would warrant exclusion from the study.
  • Systolic blood pressure of greater than 150 mmHg or diastolic blood pressure greater than 100 mmHg.
  • Serious uncontrolled cardiac rhythm disturbances which in the opinion of the investigator would warrant exclusion from the study.
  • Symptomatic orthostatic hypotension or systolic blood pressure less than 90 mm/Hg.
  • Severe, advanced peripheral vascular disease (limb threatening ischemia) or claudication resulting in the inability to walk greater than 1 block or to climb 10 stairs without interruption.
  • Lower extremity amputation.
  • Any other serious disease or condition at screening or at randomization which might affect life-expectancy or make it difficult to successfully manage and follow the subjects according to the protocol.
  • Unexplained clinically significant findings on chest x-ray.

About this study

Official title: A Randomized, Double-Blind, Comparator-Controlled Study of Pioglitazone HCl vs Glyburide in the Treatment of Subjects With Type 2 (Non-Insulin Dependent) Diabetes Mellitus and Mild to Moderate Congestive Heart Failure

The purpose of this study is to compare the safety of Pioglitazone, once daily (QD), to Glyburide in Type 2 Diabetes Subjects with Mild to Moderate Congestive Heart Failure

Read the detailed description

Approximately 16 million people in the United States have been diagnosed with type 2 diabetes, a prevalence rate of approximately 6%, and the numbers are expected to increase with the increasing age of the general population. The risk factors associated with development of type 2 diabetes, such as age, obesity, and diet and exercise habits, also contribute to the development of cardiovascular disease. Additionally, patients with diabetes are at an increased risk for development of microvascular and macrovascular disease.

With regard to congestive heart failure, the risk of congestive heart failure is increased in subjects with diabetes in the absence of coronary artery disease; in subjects with diabetes and established coronary artery disease there is a higher overall risk and greater risk for more severe congestive heart failure. There is evidence that increasing insulin sensitivity and reducing hyperinsulinemia may reduce cardiovascular risks by reducing blood pressure, improving endothelial function, and through cardiac remodeling and function.

Pioglitazone is a thiazolidinedione for the treatment of type 2 diabetes, and is an agonist of the peroxisome proliferator-activated receptor. Pioglitazone received marketing approval in the United States in 1999. As part of the approval process, Takeda fulfilled a postmarketing study evaluating the effects of pioglitazone in the treatment of type 2 diabetes in subjects with congestive heart failure in a6-month clinical study.

An independent Data Safety Monitoring Board used to monitor the overall safety pattern of the study and to conduct unblinded reviews of data found a difference in the composite endpoint of time to first event that approached nominal statistical significance in favor of glyburide. As a result, the committee recommended that Takeda terminate the trial. Consistent with regulatory agency requirements, Takeda is submitting an abbreviated report that focuses on the safety data derived from the terminated study.

Being tested
Pioglitazone, Glyburide
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
Medical subject headings
Diabetes Mellitus, Glucose Metabolism Disorders, Diabetes Mellitus, Type 2, Diabetes Mellitus, Lipoatrophic, Dyslipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PioglitazoneDrug

    Also called Actos, AD-4833

    Pioglitazone 30 mg (titrated to 45mg with tolerance), tablets, orally once daily and glyburide placebo-matching tablets, orally, once daily for up to 24 weeks.

  • GlyburideDrug

    Pioglitazone placebo-matching tablets, orally, once daily and glyburide 10 mg (titrated to 15mg with tolerance), capsules, orally, once daily for up to 24 weeks.

Study groups in NCT00521820
Study groupRoleWhat they receive
Pioglitazone QDExperimentalNot described
Receives: Drug: Pioglitazone
Glyburide QDActive comparatorNot described
Receives: Drug: Glyburide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression of Congestive Heart Failure.

    Measured: At First Event.

Secondary outcomes (10)

  1. Change from baseline in Glycosylated Hemoglobin.

    Measured: Weeks 12, 20 and Final Visit.

  2. Change from baseline in Fasting Plasma Glucose.

    Measured: At All Visits.

  3. Change from baseline in Triglycerides.

    Measured: Weeks 8, 16 and Final Visit.

  4. Change from baseline in cholesterol (total cholesterol, high-density lipoprotein and low-density lipoprotein).

    Measured: Weeks 8, 16 and Final Visit.

  5. Change from baseline in 6 Minute Walking test distance

    Measured: At Final Visit

  6. Physician & Subject Congestive Heart Failure Global Assessment Score

    Measured: At Final Visit

  7. Change in New York Heart Association classification

    Measured: At All Visits.

  8. Minnesota Living with Heart Failure Questionnaire total score.

    Measured: At Final Visit.

  9. Changes in blood pressure and heart rate.

    Measured: At All Visits.

  10. All cause mortality.

    Measured: At First Event.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2007 (estimated)
  2. Study startJun 2000
  3. Primary completionOct 2003
  4. Study completionOct 2003

Why it stopped: Higher incidence of hospitalization for congestive heart failure in pioglitazone-treated subjects compared to glyburide treated subjects.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
518 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00521820
Sponsor's protocol ID
01-00-TL-OPI-504
Other IDs
U1111-1114-1029
Status last verified
Feb 2012
First submitted
25 Aug 2007
Last updated
28 Feb 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • Giles TD, Miller AB, Elkayam U, Bhattacharya M, Perez A. Pioglitazone and heart failure: results from a controlled study in patients with type 2 diabetes mellitus and systolic dysfunction. J Card Fail. 2008 Aug;14(6):445-52. doi: 10.1016/j.cardfail.2008.02.007. Epub 2008 May 27.

    PubMed 18672190

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pioglitazone and Glyburide in people with Diabetes Mellitus, run by Takeda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Higher incidence of hospitalization for congestive heart failure in pioglitazone-treated subjects compared to glyburide treated subjects.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression of Congestive Heart Failure. (time frame: At First Event.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00521820, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2012.

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