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Diabetes MellitusPhase 3PERISCOPENCT00225277

Efficacy Study of Pioglitazone Compared to Glimepiride on Coronary Atherosclerotic Disease Progression in Subjects With Type 2 Diabetes Mellitus

A Phase 3 study testing Pioglitazone and Glimepiride in people with Diabetes Mellitus, run by Takeda at 79 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study was to determine the efficacy of pioglitazone, once daily (QD), compared to glimepiride on atherosclerotic disease measured by intravascular ultrasound. Read more about this study

Who is it for?
Ages 35 to 85 years
Conditions the study is for
Diabetes Mellitus
What is being tested?
Pioglitazone and Glimepiride
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
547 participants
Where
79 sitesin 4 countries
Study dates
Jul 2003to Oct 2007
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 35 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Females of childbearing potential who were sexually active agreed to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
  • Had a diagnosis of type 2 diabetes mellitus
  • Have received appropriate counseling on lifestyle modification for type 2 diabetes, including diet and exercise.
  • naïve to or was not currently taking antidiabetic therapy, or were currently treated with monotherapy or combination therapy.
  • Had a glycosylated hemoglobin level greater than or equal to 6.0% and less than 9% at screening if taking antidiabetic medication or greater than or equal to 6.5% and less than 10% at screening if naive to or not taking antidiabetic medication.
  • Angiographic criteria:
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  • Entire Coronary Circulation: must have angiographic evidence of coronary heart disease as defined by at least 1 lesion in a native coronary artery that has greater than or equal to 20% reduction in lumen diameter by angiographic visual estimation.
  • Left Main Coronary Artery: must not have greater than 50% reduction in lumen diameter by visual angiographic estimation.
  • Target Coronary Artery:
  • The target vessel, which includes the main artery and all of its side branches, had not undergone prior percutaneous coronary intervention or coronary artery bypass graft surgery.
  • The target vessel, which includes the main artery and all of its side branches, was not currently a candidate for intervention or a likely candidate for intervention over the next 72 weeks.
  • The target vessel was not a bypass graft.
  • The target vessel was not infarct related.
  • Had previous coronary artery bypass surgery at least six weeks prior to the qualifying intravascular ultrasound are eligible provided they are stable and meet all other entry criteria.
  • Had an intravascular ultrasound tape deemed to be of acceptable intravascular ultrasound image quality and demonstrated adherence to the intravascular ultrasound interrogation protocol, as determined by the intravascular ultrasound Core Laboratory™ assessment.

Who cannot join

  • Had type I diabetes mellitus.
  • Had participated in another investigational study, or participated in an investigational study 30 days prior to the start of this study, or who were scheduled to participate in an investigational study during the time frame of this study.
  • Male subjects who had a serum creatinine level greater than or equal to 2.0 mg/dL (greater than or equal to 177 µmol/L) (greater than or equal to 1.5 mg/dL; [greater than or equal to 133 µmol /L] if taking metformin) and female subjects who have serum creatinine greater than or equal to 1.8 mg/dL [greater than or equal to 159 µmol /L] (greater than or equal to 1.4 mg/dL [greater than or equal to 124 µmol /L] if taking metformin).
  • Had unexplained microscopic hematuria greater than +1, confirmed by repeat testing.
  • Had a history of drug abuse or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years.
  • Had clinical cardiac failure as defined by New York Heart Association class III or IV, or known left ventricular dysfunction measured as left ventricular ejection fraction less than 40%, or by current use of diuretics or angiotensin converting enzyme inhibitors for treatment of heart failure.
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  • Had an alanine transaminase level of greater than 2.5 times the upper limit of normal active liver disease, or jaundice.
  • Had a body mass index greater than 48 kg/m2 as calculated by weight (kg)/height (m2) or weight (pounds)/height (inches) 2 x 703.
  • Was required to take or intended to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may have interfered with evaluation of the study medication, including:
  • Chronically used oral glucocorticoids (eg, prednisone, cortisone, hydrocortisone, dexamethasone)
  • Niacin greater than100 mg a day, including niacin-containing products such as Advicor®
  • Chronically used steroid-joint injections
  • Thiazolidinediones
  • Sulfonylureas
  • Metformin/sulfonylurea combination
  • Other oral antidiabetic medications (eg, nateglinide [Starlix®], acarbose [Precose®]) with the exception of metformin
  • Had known or suspected malignancy or recurrence of malignancy within the past 5 years, with the exception of basal cell carcinoma and Stage 1 squamous cell carcinoma of the skin.
  • Had any disease where, in the opinion of the investigator (or designee), survival is expected to be less than 72 weeks.
  • Clinical status was unstable (ie, requiring vasopressors or intravenous inotropes, intra-aortic balloon pump, hypotension [systolic blood pressure less than 90 mm Hg]).
  • Prior to the screening visit, was scheduled for a staged cardiac intervention (percutaneous coronary intervention), peripheral vascular intervention, or coronary artery bypass graft surgery following the screening angiography.
  • In the opinion of the investigator (or designee) had clinically significant valvular heart disease likely to require surgical repair/replacement during the course of the study.
  • Had persistent, uncontrolled hypertension (ie, sitting systolic blood pressure greater than 160 mm Hg or sitting diastolic blood pressure greater than 100 mm Hg) at randomization.
  • Males who had hemoglobin less than 10.5 g/dL (less than 105 g/L) and female subjects who had hemoglobin less than 10.0 g/dL (less than 100 g/L).
  • Had a triglyceride level greater than 500 mg/dL (greater than 5.6 mmol/L).

Trial locations and contacts

79 sites in 4 countries.

79 sites in 4 countries

United States65 sites

  • Study site

    Abington, Pennsylvania

  • Study site

    Albany, New York

  • Study site

    Amarillo, Texas

  • Study site

    Baltimore, Maryland

  • Study site

    Bangor, Maine

  • Study site

    Bay Pines, Florida

  • Study site

    Birmingham, Alabama

  • Study site

    Boise, Idaho

  • Study site

    Bridgeport, Connecticut

  • Study site

    Bryn Mawr, Pennsylvania

  • Study site

    Camden, New Jersey

  • Study site

    Charlottesville, Virginia

  • Study site

    Chicago, Illinois

  • Study site

    Cincinnati, Ohio

  • Study site

    Cleveland, Ohio

  • Study site

    Columbia, Missouri

  • Study site

    Columbus, Ohio

  • Study site

    Decatur, Georgia

  • Study site

    Detroit, Michigan

  • Study site

    Duluth, Minnesota

  • Study site

    Edgewood, Kentucky

  • Study site

    Everett, Washington

  • Study site

    Farmington, Connecticut

  • Study site

    Flint, Michigan

  • Study site

    Green Bay, Wisconsin

  • Study site

    Greenville, South Carolina

  • Study site

    Hershey, Pennsylvania

  • Study site

    Houston, Texas

  • Study site

    Huntington Beach, California

  • Study site

    Jacksonville, Florida

  • Study site

    Kalamazoo, Michigan

  • Study site

    Lexington, Kentucky

  • Study site

    Los Angeles, California

  • Study site

    Louisville, Kentucky

  • Study site

    Lubbock, Texas

  • Study site

    Memphis, Tennessee

  • Study site

    Mineola, New York

  • Study site

    Minneapolis, Minnesota

  • Study site

    New Orleans, Louisiana

  • Study site

    New York, New York

  • Study site

    Norfolk, Virginia

  • Study site

    Oak Ridge, Tennessee

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Petoskey, Michigan

  • Study site

    Phoenix, Arizona

  • Study site

    Pittsburgh, Pennsylvania

  • Study site

    Pontiac, Michigan

  • Study site

    Providence, Rhode Island

  • Study site

    Richmond, Virginia

  • Study site

    Rochester, New York

  • Study site

    Royal Oak, Michigan

  • Study site

    Sacramento, California

  • Study site

    Saint Cloud, Minnesota

  • Study site

    San Antonio, Texas

  • Study site

    San Diego, California

  • Study site

    The Bronx, New York

  • Study site

    Torrance, California

  • Study site

    Troy, New York

  • Study site

    Tulsa, Oklahoma

  • Study site

    Washington D.C., District of Columbia

  • Study site

    West Islip, New York

  • Study site

    Westlake, Ohio

  • Study site

    Williamsville, New York

  • Study site

    Winston-Salem, North Carolina

  • Study site

    Ypsilanti, Michigan

Other trials in United States

Canada10 sites

  • Study site

    Edmonton, Alberta

  • Study site

    London, Ontario

  • Study site

    Montreal, Quebec

  • Study site

    Ottawa, Ontario

  • Study site

    Saint John, New Brunswick

  • Study site

    Sainte-Foy, Quebec

  • Study site

    Saskatoon, Saskatchewan

  • Study site

    Vancouver, British Columbia

  • Study site

    Victoria, British Columbia

  • Study site

    Winnepeg, Manitoba

Other trials in Canada

Argentina3 sites

  • Study site

    Ciudad de Buenos Aires

  • Study site

    Córdoba

  • Study site

    Quilmes

Other trials in Argentina

Chile1 site

  • Study site

    Santiago

Other trials in Chile

About this study

Official title: A Double-Blind, Randomized, Comparator-Controlled Study In Subjects With Type 2 Diabetes Mellitus Comparing the Effects of Pioglitazone HCl Versus Glimepiride on the Rate of Progression of Coronary Atherosclerotic Disease as Measured by Intravascular Ultrasound

The purpose of this study was to determine the efficacy of pioglitazone, once daily (QD), compared to glimepiride on atherosclerotic disease measured by intravascular ultrasound.

Read the detailed description

Diabetes is a chronic disease with multiple metabolic defects that result in hyperglycemia arising from inadequate insulin activity. Type 2 diabetes is usually the result of a progression from reduced sensitivity of hepatic and peripheral tissue cells to circulating insulin (ie, insulin resistance) to a progressive inability of the body to produce adequate insulin to overcome insulin resistance (ie, insulin deficiency due to beta-cell insufficiency) resulting in impaired glucose tolerance and ultimately overt diabetes. In the United States, an estimated 21 million people have diabetes, with type 2 diabetes occurring in approximately 90% to 95% of cases. The goal of treating type 2 diabetes is to control blood glucose and thereby prevent long-term complications. Adequate glycemic control is paramount in attempting to avert chronic complications, including blindness; renal dysfunction resulting in dialysis or renal transplantation; neuropathy; non-traumatic amputations; and macrovascular complications, including myocardial ischemia and myocardial infarction, stroke, and peripheral arterial disease. Intensive glucose management in the early stages of diabetes may help forestall such complications.

Therapeutic agents have been developed to address each of the major functional metabolic defects associated with type 2 diabetes: decreased beta-cell function, elevated hepatic glucose output, and insulin resistance. Thiazolidinediones increase glucose utilization, decrease gluconeogenesis, and increase glucose disposal by binding to nuclear receptors known as peroxisome proliferator-activated receptors. Thiazolidinediones reduce insulin resistance by enhancing insulin sensitivity in muscle cells, adipose tissue, and hepatic cells (inhibiting hepatic gluconeogenesis), with no direct impact on insulin secretion. Thus, thiazolidinediones improve glycemic control and result in reduced levels of circulating insulin without predisposing patients to hypoglycemia. Peroxisome proliferator-activated receptors are found in tissues important for insulin action, such as adipose tissue, skeletal muscle, and the liver. The greatest concentration of peroxisome proliferator-activated receptors-gamma receptors is in adipose tissue.

This study was designed to compare the effects of pioglitazone compared to glimepiride on progression of atherosclerotic disease, as measured by intravascular ultrasound.

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

What participants receive

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

  • PioglitazoneDrug

    Also called ACTOS®, AD4833

    Up to 45 mg pioglitazone (optimized for glucose control), tablets, orally, once daily for up to 72 weeks.

  • GlimepirideDrug

    Up to 4 mg of glimepiride (optimized for glucose control), tablets, orally, once daily for up to 72 weeks.

Study groups in NCT00225277
Study groupRoleWhat they receive
Pioglitazone QDExperimentalNot described
Receives: Drug: Pioglitazone
Glimepiride QDActive comparatorNot described
Receives: Drug: Glimepiride

What is being measured

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

  1. Nominal Change From Baseline in Percent Atheroma Volume

    The nominal change from baseline in percent atheroma volume for all slices of anatomically comparable segments of the target coronary artery. Assessment completed at the Week 72 visit or Final Visit if treatment was prematurely discontinued.

    Measured: Baseline and Final Visit (up to 72 weeks)

Secondary outcomes (4)

  1. Nominal Change From Baseline in Normalized Total Atheroma Volume

    The nominal change in normalized total atheroma volume as measured by the average of plaque areas for all slices of anatomically comparable segments of the target coronary artery multiplied by the mean number of matched slices in the population. Assessment completed at the Week 72 visit or Final Visit if treatment was prematurely discontinued.

    Measured: Baseline and Final Visit (up to 72 weeks)

  2. Number of Subjects Experiencing Any of the Composite Endpoint A Cardiovascular Events

    Due to low event rates, number of subjects experiencing any of the composite endpoint A cardiovascular events is being reported instead of time to first occurrence. Endpoint A conditions listed in Limitations and Caveats section.

    Measured: Up to 72 weeks

  3. Number of Subjects Experiencing Any of the Composite Endpoint B Cardiovascular Events

    Due to low event rates, number of subjects experiencing any of the composite endpoint B cardiovascular events is being reported instead of time to first occurrence. Endpoint B conditions listed in Limitations and Caveats section.

    Measured: Up to 72 weeks

  4. Number of Subjects Experiencing Any of the Composite Endpoint C Cardiovascular Events

    Due to low event rates, number of subjects experiencing any of the composite endpoint C cardiovascular events is being reported instead of time to first occurrence. Endpoint C conditions listed in Limitations and Caveats section.

    Measured: Up to 72 weeks

Timeline

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

  1. First posted23 Sep 2005 (estimated)
  2. Study startJul 2003
  3. Primary completionOct 2007
  4. Study completionOct 2007

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
547 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00225277
Sponsor's protocol ID
01-01-TL-OPI-516
Other IDs
U1111-1114-0400
Acronym
PERISCOPE
Status last verified
Feb 2012
First submitted
21 Sep 2005
Last updated
28 Feb 2012
Data monitoring committee
No

Publications

  • Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, Jure H, De Larochelliere R, Staniloae CS, Mavromatis K, Saw J, Hu B, Lincoff AM, Tuzcu EM; PERISCOPE Investigators. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA. 2008 Apr 2;299(13):1561-73. doi: 10.1001/jama.299.13.1561. Epub 2008 Mar 31.

    PubMed 18378631

  • Betteridge DJ. CHICAGO, PERISCOPE and PROactive: CV risk modification in diabetes with pioglitazone. Fundam Clin Pharmacol. 2009 Dec;23(6):675-9. doi: 10.1111/j.1472-8206.2009.00741.x. Epub 2009 Sep 10.

    PubMed 19744248

  • Nicholls SJ, Tuzcu EM, Wolski K, Bayturan O, Lavoie A, Uno K, Kupfer S, Perez A, Nesto R, Nissen SE. Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. J Am Coll Cardiol. 2011 Jan 11;57(2):153-9. doi: 10.1016/j.jacc.2010.06.055.

    PubMed 21211686

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pioglitazone and Glimepiride in people with Diabetes Mellitus, run by Takeda at 79 sites in 4 countries.

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 15 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: finished, 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.

Where is the study taking place?

The record lists 79 sites in United States, Canada, Argentina, Chile. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

Yes. Results are posted in the registry (first posted 10 Jun 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Nominal Change From Baseline in Percent Atheroma Volume (time frame: Baseline and Final Visit (up to 72 weeks)). 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 NCT00225277, which also lists 3 linked publications.

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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