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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00091949




Registration number
NCT00091949
Ethics application status
Date submitted
20/09/2004
Date registered
22/09/2004
Date last updated
28/10/2016

Titles & IDs
Public title
Insulin Resistance Intervention After Stroke Trial
Scientific title
Insulin Resistance Intervention After Stroke (IRIS) Trial
Secondary ID [1] 0 0
U01NS044876
Secondary ID [2] 0 0
R01NS044876
Universal Trial Number (UTN)
Trial acronym
IRIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 0 0
Myocardial Infarction 0 0
Diabetes 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - pioglitazone
Treatment: Drugs - placebo

Active Comparator: Pioglitazone - pioglitazone

Placebo Comparator: Placebo - inactive substance


Treatment: Drugs: pioglitazone
a thiazolidinedione drug

Treatment: Drugs: placebo
an inactive substance

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recurrent Fatal or Non-fatal Stroke, or Fatal or Non-fatal Myocardial Infarction
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Fatal or Non-fatal Stroke Alone
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Acute Coronary Syndrome - Fatal or non-fatal acute myocardial infarction or unstable angina
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
Development of Overt Diabetes
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
All Cause Mortality
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Decline in Cognitive Status - Change in modified mental status examination (3MS) score from baseline to exit. Theoretical range of 3MS scores is 0-100. Baseline scores ranged from 22-100.
Timepoint [5] 0 0
Annual measures from baseline to exit (up to 5 years)
Secondary outcome [6] 0 0
Composite Outcome of Fatal or Non-fatal Stroke, Fatal or Non-fatal MI or Episode of Serious Congestive Heart Failure
Timepoint [6] 0 0
5 years

Eligibility
Key inclusion criteria
Inclusion Criteria

1. Ages 40 years or greater at the time of randomization.

2. Ischemic stroke or TIA no less than 14 days and no more than 6 months before
randomization

3. Documentation of insulin resistance as defined by a value over 3.0 on the Homeostasis
Model Assessment of insulin sensitivity (HOMA).

4. Both ability and willingness to provide informed consent.

5. Presence of none of the exclusion criteria.
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Permanent Exclusions

1. Severely disabling stroke as indicated by an inability to participate in scheduled
follow-up activities.

2. Persons whose ischemic stroke or TIA was related to structural cardiac lesion,
significant head trauma, proximal arterial dissection or medical instrumentation.

3. Diabetes mellitus as defined by recent use of medication for diabetes as an
out-patient (*see note below) or two fasting plasma blood sugars > 126 mg/dL.

4. HgbA1c > 7.0%.

5. Irreversible medical conditions likely to affect short-term survival or ability to
participate in the study protocol. These include:

- Cancer or other chronic disease with poor prognosis (predicted survival of less
than four years).

- Severe neurologic or psychiatric disease that would complicate the evaluation of
study outcomes (e.g., dementia or schizophrenia).

6. History of intolerance to any thiazolidinedione.

7. Pregnancy or desire to become pregnant.

8. Oral contraceptive use.

9. Ongoing use of oral corticosteroids.

10. History of heart failure

11. Active liver disease as defined by known liver disease accompanied by cirrhosis,
significant cholestasis, portal hypertension, hepatic encephalopathy, hepatic
synthetic dysfunction, or expected significant loss of liver function over the course
of the study.

12. History of bladder cancer.

13. Current participation in a conflicting clinical trial. A conflicting clinical trial is
defined as a trial with any of following:

- Intervention that is known to affect the incidence of stroke or myocardial
infarction.

- Intervention that is an experimental drug.

- Outcome that includes stroke or myocardial infarction.

- Exclusion for participation in another trial.

Temporary Exclusions Persons with temporary exclusions may be enrolled as soon as the
exclusion has resolved.

1. Alanine aminotransferase (ALT) >2.5 times the upper limit of normal.

2. Hemoglobin <8.5 g/dl.

3. Moderate or severe pitting edema of the feet or legs (IRIS grade 3 or 4).

4. Carotid surgery or carotid stenting procedure scheduled (delay randomization until 2
weeks following procedure).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
Royal Prince Alfred - Camperstown
Recruitment hospital [3] 0 0
John Hunter Hospital (University of Newcastle) - New Lambton Heights
Recruitment hospital [4] 0 0
Box Hill Hospital (Eastern Health) - Box Hill
Recruitment hospital [5] 0 0
Western Hospital (University of Melbourne) - Footscray
Recruitment hospital [6] 0 0
Austin Health (National Stroke Research Institute) - Heidelberg Heights
Recruitment hospital [7] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [8] 0 0
Royal Perth - Perth
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
2050 - Camperstown
Recruitment postcode(s) [3] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3011 - Footscray
Recruitment postcode(s) [6] 0 0
3801 - Heidelberg Heights
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment postcode(s) [8] 0 0
6000 - Perth
Recruitment outside Australia
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Alabama
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Arizona
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Rome
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Aberdeen
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Airdrie
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Ashford
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Dewsbury
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Exeter
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Liverpool
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London
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Luton
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Middlesbrough
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Newcastle upon Tyne
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United Kingdom
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Torquay

Funding & Sponsors
Primary sponsor type
Other
Name
Yale University
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute of Neurological Disorders and Stroke (NINDS)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Takeda Pharmaceuticals North America, Inc.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine if pioglitazone is effective in preventing future
strokes or heart attacks among non-diabetic persons who have had a recent ischemic stroke.
Trial website
https://clinicaltrials.gov/show/NCT00091949
Trial related presentations / publications
Viscoli CM, Brass LM, Carolei A, Conwit R, Ford GA, Furie KL, Gorman M, Guarino PD, Inzucchi SE, Lovejoy AM, Parsons MW, Peduzzi PN, Ringleb PA, Schwartz GG, Spence JD, Tanne D, Young LH, Kernan WN; IRIS Trial investigators. Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial. Am Heart J. 2014 Dec;168(6):823-9.e6. doi: 10.1016/j.ahj.2014.07.016. Epub 2014 Jul 28.
Kernan WN, Viscoli CM, Demarco D, Mendes B, Shrauger K, Schindler JL, McVeety JC, Sicklick A, Moalli D, Greco P, Bravata DM, Eisen S, Resor L, Sena K, Story D, Brass LM, Furie KL, Gutmann L, Hinnau E, Gorman M, Lovejoy AM, Inzucchi SE, Young LH, Horwitz RI; IRIS Trial Investigators. Boosting enrollment in neurology trials with Local Identification and Outreach Networks (LIONs). Neurology. 2009 Apr 14;72(15):1345-51. doi: 10.1212/WNL.0b013e3181a0fda3.
Kernan W, Viscoli C, Brass L, Amatangelo M, Birch A, Clark W, Conwit R, Furie K, Gorman M, Pesapane B, Kleindorfer D, Lovejoy A, Osborne J, Silliman S, Zweifler R, Horwitz R. Boosting enrolment in clinical trials: validation of a regional network model. Clin Trials. 2011 Oct;8(5):645-53. doi: 10.1177/1740774511414925. Epub 2011 Aug 8.
Public notes

Contacts
Principal investigator
Name 0 0
Walter N. Kernan, M.D.
Address 0 0
Yale University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications