drugset / Trial / NCT03004703
ASSessing the Effect of Anti-IL-6 Treatment in Myocardial Infarction: The ASSAIL-MI Trial
Phase 2
Completed
200 enrolled
Oslo University Hospital
Norwegian University of Science and Technology · collabSouth-Eastern Norway Regional Health Authority · collabSt. Olavs Hospital · collabUniversity of Oslo · collab
RandomizedParallel-groupQuadruple-blindTreatment
Summary
The main goal of this study is to evaluate the ability of a single administration of tocilizumab to reduce myocardial damage in patients presenting with an acute ST-segment elevation myocardial infarction (STEMI). Secondary objectives are to assess the impact of treatment on: (i) final infarct size, (ii) left ventricular size and function, (iii) inflammation, (iv) extracellular matrix remodeling, (v) lipid parameters, (vi) platelet activation and additional pro- and anti-thrombotic parameters, and (vii) study drug safety and tolerability.
Timeline
- Start
- 2017-03-16
- Primary completion
- 2020-02-19
- Completion
- 2021-02-10
Outcome
Met primary endpoint
paper myocardial salvage index was larger in the tocilizumab group than in the placebo group PMID 33858620 ↗
paper adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04 PMID 33858620 ↗
Publications
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- Background Hou T, Tieu BC, Ray S, Recinos Iii A, Cui R, Tilton RG, Brasier AR. Roles of IL-6-gp130 Signaling in Vascular Inflammation. Curr Cardiol Rev. 2008 Aug;4(3):179-92. doi: 10.2174/157340308785160570.
- Background Ritschel VN, Seljeflot I, Arnesen H, Halvorsen S, Eritsland J, Fagerland MW, Andersen GO. Circulating Levels of IL-6 Receptor and gp130 and Long-Term Clinical Outcomes in ST-Elevation Myocardial Infarction. J Am Heart Assoc. 2016 Jun 13;5(6):e003014. doi: 10.1161/JAHA.115.003014.
- Background Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, Elbelghiti R, Cung TT, Bonnefoy E, Angoulvant D, Macia C, Raczka F, Sportouch C, Gahide G, Finet G, Andre-Fouet X, Revel D, Kirkorian G, Monassier JP, Derumeaux G, Ovize M. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med. 2008 Jul 31;359(5):473-81. doi: 10.1056/NEJMoa071142.
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- Background Deftereos S, Giannopoulos G, Angelidis C, Alexopoulos N, Filippatos G, Papoutsidakis N, Sianos G, Goudevenos J, Alexopoulos D, Pyrgakis V, Cleman MW, Manolis AS, Tousoulis D, Lekakis J. Anti-Inflammatory Treatment With Colchicine in Acute Myocardial Infarction: A Pilot Study. Circulation. 2015 Oct 13;132(15):1395-403. doi: 10.1161/CIRCULATIONAHA.115.017611. Epub 2015 Aug 11.
- Background Biasillo G, Leo M, Della Bona R, Biasucci LM. Inflammatory biomarkers and coronary heart disease: from bench to bedside and back. Intern Emerg Med. 2010 Jun;5(3):225-33. doi: 10.1007/s11739-010-0361-1. Epub 2010 Feb 25.
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- Background Oldfield V, Dhillon S, Plosker GL. Tocilizumab: a review of its use in the management of rheumatoid arthritis. Drugs. 2009;69(5):609-32. doi: 10.2165/00003495-200969050-00007.
- Background Eitel I, de Waha S, Wohrle J, Fuernau G, Lurz P, Pauschinger M, Desch S, Schuler G, Thiele H. Comprehensive prognosis assessment by CMR imaging after ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2014 Sep 23;64(12):1217-26. doi: 10.1016/j.jacc.2014.06.1194.
- Background Erlinge D, Gotberg M, Lang I, Holzer M, Noc M, Clemmensen P, Jensen U, Metzler B, James S, Botker HE, Omerovic E, Engblom H, Carlsson M, Arheden H, Ostlund O, Wallentin L, Harnek J, Olivecrona GK. Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. The CHILL-MI trial: a randomized controlled study of the use of central venous catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. J Am Coll Cardiol. 2014 May 13;63(18):1857-65. doi: 10.1016/j.jacc.2013.12.027. Epub 2014 Feb 5.
- Background Atar D, Arheden H, Berdeaux A, Bonnet JL, Carlsson M, Clemmensen P, Cuvier V, Danchin N, Dubois-Rande JL, Engblom H, Erlinge D, Firat H, Halvorsen S, Hansen HS, Hauke W, Heiberg E, Koul S, Larsen AI, Le Corvoisier P, Nordrehaug JE, Paganelli F, Pruss RM, Rousseau H, Schaller S, Sonou G, Tuseth V, Veys J, Vicaut E, Jensen SE. Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results. Eur Heart J. 2015 Jan 7;36(2):112-9. doi: 10.1093/eurheartj/ehu331. Epub 2014 Sep 1.
- Background Ibanez B, Macaya C, Sanchez-Brunete V, Pizarro G, Fernandez-Friera L, Mateos A, Fernandez-Ortiz A, Garcia-Ruiz JM, Garcia-Alvarez A, Iniguez A, Jimenez-Borreguero J, Lopez-Romero P, Fernandez-Jimenez R, Goicolea J, Ruiz-Mateos B, Bastante T, Arias M, Iglesias-Vazquez JA, Rodriguez MD, Escalera N, Acebal C, Cabrera JA, Valenciano J, Perez de Prado A, Fernandez-Campos MJ, Casado I, Garcia-Rubira JC, Garcia-Prieto J, Sanz-Rosa D, Cuellas C, Hernandez-Antolin R, Albarran A, Fernandez-Vazquez F, de la Torre-Hernandez JM, Pocock S, Sanz G, Fuster V. Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial. Circulation. 2013 Oct 1;128(14):1495-503. doi: 10.1161/CIRCULATIONAHA.113.003653. Epub 2013 Sep 3.
- Background Eitel I, Stiermaier T, Rommel KP, Fuernau G, Sandri M, Mangner N, Linke A, Erbs S, Lurz P, Boudriot E, Mende M, Desch S, Schuler G, Thiele H. Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial. Eur Heart J. 2015 Nov 21;36(44):3049-57. doi: 10.1093/eurheartj/ehv463. Epub 2015 Sep 17.
- Background Galderisi M, Henein MY, D'hooge J, Sicari R, Badano LP, Zamorano JL, Roelandt JR; European Association of Echocardiography. Recommendations of the European Association of Echocardiography: how to use echo-Doppler in clinical trials: different modalities for different purposes. Eur J Echocardiogr. 2011 May;12(5):339-53. doi: 10.1093/ejechocard/jer051.
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- Background Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grogaard HK, Bjornerheim R, Brekke M, Muller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006 Sep 21;355(12):1199-209. doi: 10.1056/NEJMoa055706.
- Background Gibbons RJ, Valeti US, Araoz PA, Jaffe AS. The quantification of infarct size. J Am Coll Cardiol. 2004 Oct 19;44(8):1533-42. doi: 10.1016/j.jacc.2004.06.071.
- Background Engblom H, Heiberg E, Erlinge D, Jensen SE, Nordrehaug JE, Dubois-Rande JL, Halvorsen S, Hoffmann P, Koul S, Carlsson M, Atar D, Arheden H. Sample Size in Clinical Cardioprotection Trials Using Myocardial Salvage Index, Infarct Size, or Biochemical Markers as Endpoint. J Am Heart Assoc. 2016 Mar 9;5(3):e002708. doi: 10.1161/JAHA.115.002708.
- Kindberg KM, Broch K, Andersen GO, Anstensrud AK, Akra S, Woxholt S, Tollefsen IM, Ueland T, Amundsen BH, Klow NE, Halvorsen B, Dahl TB, Huse C, Murphy SL, Damas JK, Opdahl A, Wiseth R, Gullestad L, Aukrust P, Santos-Gallego C, Seljeflot I, Stokke MK, Helseth R. Neutrophil Extracellular Traps in ST-Segment Elevation Myocardial Infarction: Reduced by Tocilizumab and Associated With Infarct Size. JACC Adv. 2024 Aug 15;3(9):101193. doi: 10.1016/j.jacadv.2024.101193. eCollection 2024 Sep.
- Woxholt S, Ueland T, Aukrust P, Anstensrud AK, Broch K, Tollefsen IM, Ryan L, Bendz B, Hopp E, Klow NE, Seljeflot I, Halvorsen B, Dahl TB, Huse C, Andersen GO, Gullestad L, Wiseth R, Amundsen BH, Damas JK, Kleveland O. Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab. Open Heart. 2023 Aug;10(2):e002301. doi: 10.1136/openhrt-2023-002301.
- Broch K, Anstensrud AK, Woxholt S, Sharma K, Tollefsen IM, Bendz B, Aakhus S, Ueland T, Amundsen BH, Damas JK, Berg ES, Bjorkelund E, Bendz C, Hopp E, Kleveland O, Stensaeth KH, Opdahl A, Klow NE, Seljeflot I, Andersen GO, Wiseth R, Aukrust P, Gullestad L. Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol. 2021 Apr 20;77(15):1845-1855. doi: 10.1016/j.jacc.2021.02.049.
- Anstensrud AK, Woxholt S, Sharma K, Broch K, Bendz B, Aakhus S, Ueland T, Amundsen BH, Damas JK, Hopp E, Kleveland O, Stensaeth KH, Opdahl A, Klow NE, Seljeflot I, Andersen GO, Wiseth R, Aukrust P, Gullestad L. Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI). Open Heart. 2019 Oct 15;6(2):e001108. doi: 10.1136/openhrt-2019-001108. eCollection 2019.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Tocilizumab | Monoclonal antibody | 280 mg | Intravenous |