Insulin Resistance Intervention After Stroke Trial

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.

Timeline

Start

2005-02

Primary completion

2015-11

Completion

2015-11

Publications

• Background 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.
• Background 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.
• Background 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.
• Ridha M, Zhang C, McCullough S, Viscoli CM, Sharma R, Kamel H, Merkler AE. Silent Myocardial Infarction and Risk of Stroke Recurrence: A Post Hoc Analysis of the IRIS Trial. J Am Heart Assoc. 2025 Feb 18;14(4):e037663. doi: 10.1161/JAHA.124.037663. Epub 2025 Feb 8.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications