Clinical trial NCT00091949: Insulin Resistance Intervention After Stroke Trial
Official title: Insulin Resistance Intervention After Stroke (IRIS) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Stroke
Myocardial Infarction
Diabetes
Keywords: stroke
heart attack
diabetes
pioglitazone
insulin resistance
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Takeda Pharmaceuticals North America, Inc.
First posted: 2004-09-22
Enrollment: 3876
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Among patients throughout the world who experience a transient ischemic attack (TIA)or ischemic stroke, subsequent stroke and heart attack are major causes of death and disability. Within 4 years of the initial TIA or ischemic stroke, 16 percent of patients will have a recurrent stroke and 9 percent will have a heart attack. Prevention of further vascular events, therefore, is critically important to the health of patients with stroke.

The IRIS trial will test a new treatment strategy based on evidence linking insulin resistance to increased risk for stroke and other vascular diseases. Insulin resistance is a condition in which insulin, a normal human hormone, does not work effectively because the body is resistant to its effects. This condition can lead to diabetes and is thought to cause blood vessel disease, including stroke and heart attack, in patients with and without diabetes.

Insulin resistance affects up to 50% of stroke patients and is effectively modified with thiazolidinedione (TZD) drugs used to treat type 2 diabetes. In addition to reducing insulin resistance, these drugs have other favorable effects on blood vessels, reduce blood vessel inflammation, and potentially prevent atherosclerosis. Currently marketed TZDs include rosiglitazone and pioglitazone.

The IRIS is a clinical trial that will enroll 3936 subjects at approximately 170 hospitals in Australia, Canada, Germany, Israel, Italy, the United Kingdom (UK) and the US. After an initial screening blood test, each participant will be randomly assigned to take either pioglitazone or placebo tablets. Recruitment will be completed during 2005-2012, and all participants will be followed for a minimum of 3 years.

Eligibility 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.

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).

Primary outcomes:
measure: Recurrent Fatal or Non-fatal Stroke, or Fatal or Non-fatal Myocardial Infarction
timeFrame: Up to 5 years
Secondary outcomes:
measure: Fatal or Non-fatal Stroke Alone
timeFrame: 5 years
measure: Acute Coronary Syndrome
timeFrame: 5 years
measure: Development of Overt Diabetes
timeFrame: 5 years
measure: All Cause Mortality
timeFrame: 5 years
measure: Decline in Cognitive Status
timeFrame: Annual measures from baseline to exit (up to 5 years)
measure: Composite Outcome of Fatal or Non-fatal Stroke, Fatal or Non-fatal MI or Episode of Serious Congestive Heart Failure
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Colton
country: United States
facility: Shanti Clinical Trials (NINDS-CRC site)
state: California
city: Fresno
country: United States
facility: UCSF-Fresno
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California-Davis
state: California
city: San Diego
country: United States
facility: University of California
state: California
city: San Francisco
country: United States
facility: University of California
state: California
city: Denver
country: United States
facility: Denver Health and Hospital Authority
state: Colorado
city: Hartford
country: United States
facility: Hartford
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: National Rehabilitation Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Melbourne
country: United States
facility: MIMA Century Research Associates
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Neurological Associates (NINDS-CRC site)
state: Florida
city: Tampa
country: United States
facility: Floria Neurovascular Institute
state: Florida
city: Chicago
country: United States
facility: Cook County (Stroger) Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital (NINDS-CRC site)
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Saint Charles
country: United States
facility: Tri-City Neruology (NINDS-CRC site)
state: Illinois
city: Elkhart
country: United States
facility: Indiana Medical Research
state: Indiana
city: Valparaiso
country: United States
facility: Associates In Neurology (NINDS-CRC site)
state: Indiana
city: Des Moines
country: United States
facility: Iowa Health Des Moines Clinical Trials Office
state: Iowa
city: Des Moines
country: United States
facility: Ruan Neuroscience Center/Mercy Medical Center
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Waterloo
country: United States
facility: Northeast Iowa Medical Education Foundation (NINDS-CRC site)
state: Iowa
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Research Foundation
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Rockport
country: United States
facility: Penobscot Bay Neurology
state: Maine
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: Boston
country: United States
facility: Caritas St. Elizabeth's Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Robbinsdale
country: United States
facility: Minneapolis Clinic of Neurology
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic (NINDS-CRC site)
state: Mississippi
city: Kansas City
country: United States
facility: St. Luke's Brain and Stroke Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Saint Louis
country: United States
facility: St. John's Mercy Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Great Falls
country: United States
facility: Advanced Neurology Specialists
state: Montana
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: West Orange
country: United States
facility: Kessler Medical Rehab Research Corp
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate
state: New York
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: Buffalo
country: United States
facility: SUNY Buffalo
state: New York
city: New York
country: United States
facility: St. Vincent's Hospital Manhattan
state: New York
city: New York
country: United States
facility: Cornell University
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: West Seneca
country: United States
facility: Southtowns Neurology of WNY (NINDS-CRC site)
state: New York
city: White Plains
country: United States
facility: Burke Medical Research Institute
state: New York
city: Winston-Salem
country: United States
facility: Clinical Research of Winston-Salem
state: North Carolina
city: Winston-Salem
country: United States
facility: Guilford Neurologic Associates
state: North Carolina
city: Grand Forks
country: United States
facility: Altru Health System
state: North Dakota
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Metrohealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Lankenau Institute for Medical Research
state: Pennsylvania
city: Hershey
country: United States
facility: Penn Stat-Hershey Medical Center (NINDS-CRC site)
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Singer Research Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Memphis
country: United States
facility: University of Tennessee
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Dallas
country: United States
facility: University of Texas, Southwestern
state: Texas
city: Houston
country: United States
facility: Methodist Neurological Institute
state: Texas
city: San Antonio
country: United States
facility: University of Texas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Norfolk
country: United States
facility: Sentara Medical Group
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: New South Wales
city: Camperstown
country: Australia
facility: Royal Prince Alfred
state: New South Wales
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital (University of Newcastle)
state: New South Wales
city: Box Hill
country: Australia
facility: Box Hill Hospital (Eastern Health)
state: Victoria
city: Footscray
country: Australia
facility: Western Hospital (University of Melbourne)
state: Victoria
city: Heidelberg Heights
country: Australia
facility: Austin Health (National Stroke Research Institute)
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth
state: Western Australia
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Lethbridge
country: Canada
facility: Center for Neurologic Research
state: Alberta
city: Victoria
country: Canada
facility: Vancouver Island Health Research Centre
state: British Columbia
city: London
country: Canada
facility: Robarts Research Institute
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital-General Campus
state: Ontario
city: Thunder Bay
country: Canada
facility: Intermountain Research Consultants
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Hôpital Charles LeMoyne
state: Quebec
city: Montreal
country: Canada
facility: McGill-Montreal General
state: Quebec
city: Montreal
country: Canada
facility: McGill-Jewish General
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Affilie Universitaire de Quebec
state: Quebec
city: Montreal
country: Canada
facility: CHUM-Centre de recherche, Hôpital Notre-Dame
city: Altenburg
country: Germany
facility: Klinikum Altenburger Land
city: Bad Neustadt
country: Germany
facility: Neurologische Klinik
city: Dresden
country: Germany
facility: University Hospital-Dresden
city: Duesseldorf
country: Germany
facility: University Duesseldorf/Heinrich-Heine University
city: Erlangen
country: Germany
facility: University of Erlangen
city: Essen
country: Germany
facility: Alfried Krupp Hospital
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
city: Freiburg
country: Germany
facility: Freiburg University
city: Griefswald
country: Germany
facility: Ernst-Moritz-Arndt-University Greifswald
city: Halle
country: Germany
facility: Martin-Luther-Universitaet Halle-Wittenberg
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: University Heidelberg
city: Jena
country: Germany
facility: Friedrich Schiller-University Jena
city: Mainz
country: Germany
facility: University Hospital Mainz
city: Muenster
country: Germany
facility: University Hospital Muenster
city: Munich
country: Germany
facility: Klinikum der Universitat Muenchen
city: Ulm
country: Germany
facility: University of Ulm
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: B'nai Zion Medical Center
city: Haifa
country: Israel
facility: Bnai-Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center-Golda Campus
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Medical Center
city: Genoa
country: Italy
facility: Genoa University Hospital
city: Laquila
country: Italy
facility: University of Laquila
city: Milan
country: Italy
facility: University Vita Salute San Raffaele
city: Pavia
country: Italy
facility: IRCCS FONdazione Istituto Neurologico C. Mondino
city: Perugia
country: Italy
facility: University of Perugia
city: Roma
country: Italy
facility: University of Rome (S. Andrea Hospital)
city: Rome
country: Italy
facility: University of Rome La Sapienza
city: Rome
country: Italy
facility: Sacred Heart Catholic University
city: Vibo Valentia
country: Italy
facility: Jazzolino Hospital
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth
state: Dorset
city: Margate
country: United Kingdom
facility: Queen Elizabeth The Queen Mother Hospital
state: Kent
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: Lancashire
city: Ashington
country: United Kingdom
facility: Wansbeck General Hospital
state: Northumberland
city: Glasgow
country: United Kingdom
facility: Stobhill Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
state: Scotland
city: Glasgow
country: United Kingdom
facility: Southern General Hospital
state: Scotland
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital Gateshead
state: Tyne And Wear
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Airdrie
country: United Kingdom
facility: Monklands Hospital
city: Ashford
country: United Kingdom
facility: William Harvey Hospital
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Foundation NHS Trust (Cambridge)
city: Cheshire
country: United Kingdom
facility: Countess of Chester Foundation Trust
city: Dewsbury
country: United Kingdom
facility: Dewsbury District Hospital
city: Essex
country: United Kingdom
facility: Southend University Hospital
city: Exeter
country: United Kingdom
facility: Devon PCT
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Halifax
country: United Kingdom
facility: Calderdale Royal Hospital
city: Liverpool
country: United Kingdom
facility: The Royal Liverpool and Broadgreen University Hospitals
city: Liverpool
country: United Kingdom
facility: University Hospital Aintree
city: London
country: United Kingdom
facility: Kings College London
city: London
country: United Kingdom
facility: Saint Georges University of London
city: Luton
country: United Kingdom
facility: Luton and Dubstable Hospital
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle upon Tyne
city: Torquay
country: United Kingdom
facility: Torbay Hospital (South Devon Healthcare NHS Foundation Trust)
city: Tyne And Wear
country: United Kingdom
facility: North Tyneside General Hospital
Study officials:
affiliation: Yale University
name: Walter N. Kernan, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: Spence JD, Viscoli CM, Inzucchi SE, Dearborn-Tomazos J, Ford GA, Gorman M, Furie KL, Lovejoy AM, Young LH, Kernan WN; IRIS Investigators. Pioglitazone Therapy in Patients With Stroke and Prediabetes: A Post Hoc Analysis of the IRIS Randomized Clinical Trial. JAMA Neurol. 2019 May 1;76(5):526-535. doi: 10.1001/jamaneurol.2019.0079.
citation: Young LH, Viscoli CM, Schwartz GG, Inzucchi SE, Curtis JP, Gorman MJ, Furie KL, Conwit R, Spatz ES, Lovejoy A, Abbott JD, Jacoby DL, Kolansky DM, Ling FS, Pfau SE, Kernan WN; IRIS Investigators. Heart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone. Circulation. 2018 Sep 18;138(12):1210-1220. doi: 10.1161/CIRCULATIONAHA.118.034763.
citation: Yaghi S, Furie KL, Viscoli CM, Kamel H, Gorman M, Dearborn J, Young LH, Inzucchi SE, Lovejoy AM, Kasner SE, Conwit R, Kernan WN; IRIS Trial Investigators. Pioglitazone Prevents Stroke in Patients With a Recent Transient Ischemic Attack or Ischemic Stroke: A Planned Secondary Analysis of the IRIS Trial (Insulin Resistance Intervention After Stroke). Circulation. 2018 Jan 30;137(5):455-463. doi: 10.1161/CIRCULATIONAHA.117.030458. Epub 2017 Oct 30.
citation: Kernan WN, Viscoli CM, Dearborn JL, Kent DM, Conwit R, Fayad P, Furie KL, Gorman M, Guarino PD, Inzucchi SE, Stuart A, Young LH; Insulin Resistance Intervention After Stroke (IRIS) Trial Investigators. Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction. JAMA Neurol. 2017 Nov 1;74(11):1319-1327. doi: 10.1001/jamaneurol.2017.2136.
citation: Stuart AC, Sico JJ, Viscoli CM, Tayal AH, Inzucchi SE, Ford GA, Furie KL, Cote R, Spence JD, Tanne D, Kernan WN. Taking care of volunteers in a stroke trial: a new assisted-management strategy. Stroke Vasc Neurol. 2016 Oct 25;1(3):108-114. doi: 10.1136/svn-2016-000029. eCollection 2016 Sep.
citation: Furie KL, Viscoli CM, Gorman M, Ford GA, Young LH, Inzucchi SE, Guarino PD, Lovejoy AM, Conwit R, Tanne D, Kernan WN; IRIS Trial Investigators. Effects of pioglitazone on cognitive function in patients with a recent ischaemic stroke or TIA: a report from the IRIS trial. J Neurol Neurosurg Psychiatry. 2018 Jan;89(1):21-27. doi: 10.1136/jnnp-2017-316361. Epub 2017 Sep 22.
citation: Young LH, Viscoli CM, Curtis JP, Inzucchi SE, Schwartz GG, Lovejoy AM, Furie KL, Gorman MJ, Conwit R, Abbott JD, Jacoby DL, Kolansky DM, Pfau SE, Ling FS, Kernan WN; IRIS Investigators. Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus. Circulation. 2017 May 16;135(20):1882-1893. doi: 10.1161/CIRCULATIONAHA.116.024863. Epub 2017 Feb 28.
citation: Viscoli CM, Inzucchi SE, Young LH, Insogna KL, Conwit R, Furie KL, Gorman M, Kelly MA, Lovejoy AM, Kernan WN; IRIS Trial Investigators. Pioglitazone and Risk for Bone Fracture: Safety Data From a Randomized Clinical Trial. J Clin Endocrinol Metab. 2017 Mar 1;102(3):914-922. doi: 10.1210/jc.2016-3237.
citation: Inzucchi SE, Viscoli CM, Young LH, Furie KL, Gorman M, Lovejoy AM, Dagogo-Jack S, Ismail-Beigi F, Korytkowski MT, Pratley RE, Schwartz GG, Kernan WN; IRIS Trial Investigators. Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. Diabetes Care. 2016 Oct;39(10):1684-92. doi: 10.2337/dc16-0798. Epub 2016 Jul 27.
citation: Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP Jr, Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O'Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR; IRIS Trial Investigators. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. 2016 Apr 7;374(14):1321-31. doi: 10.1056/NEJMoa1506930. Epub 2016 Feb 17.
citation: Kernan WN, Inzucchi SE. Metabolic rehabilitation: science gathers to support a new intervention to prevent stroke. Stroke. 2011 Dec;42(12):3333-5. doi: 10.1161/STROKEAHA.111.632489. Epub 2011 Oct 13. No abstract available.