Multicenter Investigation of Limitation of Infarct Size (MILIS)

NCT00000493 | Completed Phase 3

• 1 other identifier: 12
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To assess the ability of two separate therapeutic interventions, propranolol and hyaluronidase, to limit the ultimate size of an acute myocardial infarction. A secondary objective was to assess the influence of these therapies upon ventricular function and morbidity following myocardial infarction.

Conditions

Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Infarction; Myocardial Ischemia

Interventions

propranolol DRUG

hyaluronidase DRUG

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Men and women, under age 75. Documented myocardial infarction which could be treated within 18 hours of onset of ischemic symptoms.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Related Publications (36)

• Rude RE, Poole WK, Muller JE, Turi Z, Rutherford J, Parker C, Roberts R, Raabe DS Jr, Gold HK, Stone PH, et al. Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients. Am J Cardiol. 1983 Nov 1;52(8):936-42. doi: 10.1016/0002-9149(83)90508-8.

  PMID: 6356862 BACKGROUND

• Hackel DB, Reimer KA, Ideker RE, Mikat EM, Hartwell TD, Parker CB, Braunwald EB, Buja M, Gold HK, Jaffe AS, et al. Comparison of enzymatic and anatomic estimates of myocardial infarct size in man. Circulation. 1984 Nov;70(5):824-35. doi: 10.1161/01.cir.70.5.824.

  PMID: 6488496 BACKGROUND

• Mukharji J, Rude RE, Poole WK, Gustafson N, Thomas LJ Jr, Strauss HW, Jaffe AS, Muller JE, Roberts R, Raabe DS Jr, et al. Risk factors for sudden death after acute myocardial infarction: two-year follow-up. Am J Cardiol. 1984 Jul 1;54(1):31-6. doi: 10.1016/0002-9149(84)90299-6.

  PMID: 6741836 BACKGROUND

• Roberts R, Croft C, Gold HK, Hartwell TD, Jaffe AS, Muller JE, Mullin SM, Parker C, Passamani ER, Poole WK, et al. Effect of propranolol on myocardial-infarct size in a randomized blinded multicenter trial. N Engl J Med. 1984 Jul 26;311(4):218-25. doi: 10.1056/NEJM198407263110403.

  PMID: 6377070 BACKGROUND

• Croft CH, Rude RE, Lewis SE, Parkey RW, Poole WK, Parker C, Fox N, Roberts R, Strauss HW, Thomas LJ, et al. Comparison of left ventricular function and infarct size in patients with and without persistently positive technetium-99m pyrophosphate myocardial scintigrams after myocardial infarction: analysis of 357 patients. Am J Cardiol. 1984 Feb 1;53(4):421-8. doi: 10.1016/0002-9149(84)90006-7.

  PMID: 6320623 BACKGROUND

• Muller JE (Ed.), Braunwald E, Mock MB, et al (Assoc. Eds.): National Heart, Lung, and Blood Institute Multicenter Investigation of the Limitation of Infarct Size (MILIS). Design and Methods of the Clinical Trial. An Investigation of Beta-Blockade and Hyaluronidase for Treatment of Acute Myocardial Infarction. AHA Monograph 100:1-134, 1984.

  BACKGROUND

• Turi ZG, Rutherford JD, Roberts R, Muller JE, Jaffe AS, Rude RE, Parker C, Raabe DS, Stone PH, Hartwell TD, et al. Electrocardiographic, enzymatic and scintigraphic criteria of acute myocardial infarction as determined from study of 726 patients (A MILIS Study). Am J Cardiol. 1985 Jun 1;55(13 Pt 1):1463-8. doi: 10.1016/0002-9149(85)90954-3.

  PMID: 2988325 BACKGROUND

• Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, Poole WK, Passamani E, Roberts R, Robertson T, et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med. 1985 Nov 21;313(21):1315-22. doi: 10.1056/NEJM198511213132103.

  PMID: 2865677 BACKGROUND

• Muller JE, Turi ZG, Stone PH, Rude RE, Raabe DS, Jaffe AS, Gold HK, Gustafson N, Poole WK, Passamani E, Smith TW, Braunwald E; MILIS Study Group. Digoxin therapy and mortality after myocardial infarction. Experience in the MILIS Study. N Engl J Med. 1986 Jan 30;314(5):265-71. doi: 10.1056/NEJM198601303140501.

  PMID: 3510391 BACKGROUND

• Wheelan K, Mukharji J, Rude RE, Poole WK, Gustafson N, Thomas LJ Jr, Strauss HW, Jaffe AS, Muller JE, Roberts R, et al. Sudden death and its relation to QT-interval prolongation after acute myocardial infarction: two-year follow-up. Am J Cardiol. 1986 Apr 1;57(10):745-50. doi: 10.1016/0002-9149(86)90606-5.

  PMID: 2870632 BACKGROUND

• Rude RE, Buja LM, Willerson JT. Propranolol in acute myocardial infarction: the MILIS experience. Am J Cardiol. 1986 Apr 25;57(12):38F-42F. doi: 10.1016/0002-9149(86)90887-8.

  PMID: 2871744 BACKGROUND

• Hyaluronidase therapy for acute myocardial infarction: results of a randomized, blinded, multicenter trial. MILIS Study Group. Am J Cardiol. 1986 Jun 1;57(15):1236-43. doi: 10.1016/0002-9149(86)90195-5.

  PMID: 2872794 BACKGROUND

• Turi ZG, Stone PH, Muller JE, Parker C, Rude RE, Raabe DE, Jaffe AS, Hartwell TD, Robertson TL, Braunwald E. Implications for acute intervention related to time of hospital arrival in acute myocardial infarction. Am J Cardiol. 1986 Aug 1;58(3):203-9. doi: 10.1016/0002-9149(86)90047-0.

  PMID: 3739907 BACKGROUND

• Croft CH, Rude RE, Gustafson N, Stone PH, Poole WK, Roberts R, Strauss HW, Raabe DS Jr, Thomas LJ, Jaffe AS, et al. Abrupt withdrawal of beta-blockade therapy in patients with myocardial infarction: effects on infarct size, left ventricular function, and hospital course. Circulation. 1986 Jun;73(6):1281-90. doi: 10.1161/01.cir.73.6.1281.

  PMID: 3009050 BACKGROUND

• Lamas GA, Muller JE, Turi ZG, Stone PH, Rutherford JD, Jaffe AS, Raabe DS, Rude RE, Mark DB, Califf RM, et al. A simplified method to predict occurrence of complete heart block during acute myocardial infarction. Am J Cardiol. 1986 Jun 1;57(15):1213-9. doi: 10.1016/0002-9149(86)90191-8.

  PMID: 3717016 BACKGROUND

• Stone PH, Turi ZG, Muller JE, Parker C, Hartwell T, Rutherford JD, Jaffe AS, Raabe DS, Passamani ER, Willerson JT, et al. Prognostic significance of the treadmill exercise test performance 6 months after myocardial infarction. J Am Coll Cardiol. 1986 Nov;8(5):1007-17. doi: 10.1016/s0735-1097(86)80374-6.

  PMID: 2876018 BACKGROUND

• Tofler GH, Stone PH, Muller JE, Willich SN, Davis VG, Poole WK, Strauss HW, Willerson JT, Jaffe AS, Robertson T, et al. Effects of gender and race on prognosis after myocardial infarction: adverse prognosis for women, particularly black women. J Am Coll Cardiol. 1987 Mar;9(3):473-82. doi: 10.1016/s0735-1097(87)80038-4.

  PMID: 3819194 BACKGROUND

• Willich SN, Stone PH, Muller JE, Tofler GH, Crowder J, Parker C, Rutherford JD, Turi ZG, Robertson T, Passamani E, et al. High-risk subgroups of patients with non-Q wave myocardial infarction based on direction and severity of ST segment deviation. Am Heart J. 1987 Nov;114(5):1110-9. doi: 10.1016/0002-8703(87)90186-4.

  PMID: 3673877 BACKGROUND

• Cox DA, Stone PH, Muller JE, Parker C, Hartwell TD, Rutherford JD, Roberts R, Jaffe AS, Hackel DB, Passamani ER, et al. Prognostic implications of an early peak in plasma MB creatine kinase in patients with acute myocardial infarction. J Am Coll Cardiol. 1987 Nov;10(5):979-90. doi: 10.1016/s0735-1097(87)80334-0.

  PMID: 3312368 BACKGROUND

• Tofler GH, Stone PH, Muller JE, Rutherford JD, Willich SN, Gustafson NF, Poole WK, Sobel BE, Willerson JT, Robertson T, et al. Prognosis after cardiac arrest due to ventricular tachycardia or ventricular fibrillation associated with acute myocardial infarction (the MILIS Study). Multicenter Investigation of the Limitation of Infarct Size. Am J Cardiol. 1987 Oct 1;60(10):755-61. doi: 10.1016/0002-9149(87)91018-6.

  PMID: 3661389 BACKGROUND

• Stone PH, Raabe DS, Jaffe AS, Gustafson N, Muller JE, Turi ZG, Rutherford JD, Poole WK, Passamani E, Willerson JT, et al. Prognostic significance of location and type of myocardial infarction: independent adverse outcome associated with anterior location. J Am Coll Cardiol. 1988 Mar;11(3):453-63. doi: 10.1016/0735-1097(88)91517-3.

  PMID: 3278032 BACKGROUND

• Hands ME, Cook EF, Stone PH, Muller JE, Hartwell T, Sobel BE, Roberts R, Braunwald E, Rutherford JD. Electrocardiographic diagnosis of myocardial infarction in the presence of complete left bundle branch block. Am Heart J. 1988 Jul;116(1 Pt 1):23-31. doi: 10.1016/0002-8703(88)90245-1.

  PMID: 3394629 BACKGROUND

• Muller JE, Rude RE, Braunwald E, Hartwell TD, Roberts R, Sobel BE, Ritter C, Parker CB, Jaffe AS, Stone PH, et al. Myocardial infarct extension: occurrence, outcome, and risk factors in the Multicenter Investigation of Limitation of Infarct Size. Ann Intern Med. 1988 Jan;108(1):1-6. doi: 10.7326/0003-4819-108-1-1.

  PMID: 3337484 BACKGROUND

• Roberts R, Braunwald E, Muller JE, Croft C, Gold HK, Hartwell TD, Jaffe AS, Mullin SM, Parker C, Passamani ER, et al. Effect of hyaluronidase on mortality and morbidity in patients with early peaking of plasma creatine kinase MB and non-transmural ischaemia. Multicentre investigation for the limitation of infarct size (MILIS). Br Heart J. 1988 Oct;60(4):290-8. doi: 10.1136/hrt.60.4.290.

  PMID: 3056476 BACKGROUND

• Lee RT, Lee TH, Poole WK, Gustafson N, Stone PH, Jaffe AS, Muller JE, Sobel BE, Roberts R, Braunwald E. Rate of disappearance of creatine kinase-MB after acute myocardial infarction: clinical determinants of variability. Am Heart J. 1988 Dec;116(6 Pt 1):1493-9. doi: 10.1016/0002-8703(88)90734-x.

  PMID: 3195433 BACKGROUND

• Tofler GH, Muller JE, Stone PH, Willich SN, Davis VG, Poole WK, Robertson T, Braunwald E. Pericarditis in acute myocardial infarction: characterization and clinical significance. Am Heart J. 1989 Jan;117(1):86-92. doi: 10.1016/0002-8703(89)90660-1.

  PMID: 2643287 BACKGROUND

• Pohjola-Sintonen S, Muller JE, Stone PH, Willich SN, Antman EM, Davis VG, Parker CB, Braunwald E. Ventricular septal and free wall rupture complicating acute myocardial infarction: experience in the Multicenter Investigation of Limitation of Infarct Size. Am Heart J. 1989 Apr;117(4):809-18. doi: 10.1016/0002-8703(89)90617-0.

  PMID: 2648779 BACKGROUND

• Hands ME, Rutherford JD, Muller JE, Davies G, Stone PH, Parker C, Braunwald E. The in-hospital development of cardiogenic shock after myocardial infarction: incidence, predictors of occurrence, outcome and prognostic factors. The MILIS Study Group. J Am Coll Cardiol. 1989 Jul;14(1):40-6; discussion 47-8. doi: 10.1016/0735-1097(89)90051-x.

  PMID: 2738272 BACKGROUND

• Stone PH, Muller JE, Hartwell T, York BJ, Rutherford JD, Parker CB, Turi ZG, Strauss HW, Willerson JT, Robertson T, et al. The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. The MILIS Study Group. J Am Coll Cardiol. 1989 Jul;14(1):49-57. doi: 10.1016/0735-1097(89)90053-3.

  PMID: 2661630 BACKGROUND

• Tofler GH, Stone PH, Muller JE, Braunwald E. Mortality for women after acute myocardial infarction: MILIS Study Group. Am J Cardiol. 1989 Jul 15;64(3):256. doi: 10.1016/0002-9149(89)90476-1. No abstract available.

  PMID: 2741839 BACKGROUND

• Barzilai B, Davis VG, Stone PH, Jaffe AS. Prognostic significance of mitral regurgitation in acute myocardial infarction. The MILIS Study Group. Am J Cardiol. 1990 May 15;65(18):1169-75. doi: 10.1016/0002-9149(90)90968-7.

  PMID: 2337024 BACKGROUND

• Tofler GH, Stone PH, Maclure M, Edelman E, Davis VG, Robertson T, Antman EM, Muller JE. Analysis of possible triggers of acute myocardial infarction (the MILIS study). Am J Cardiol. 1990 Jul 1;66(1):22-7. doi: 10.1016/0002-9149(90)90729-k.

  PMID: 2193495 BACKGROUND

• Brezinski D, Stone PH, Muller JE, Tofler GH, Davis V, Parker C, Hartley LH, Braunwald E. Prognostic significance of the Karnofsky Performance Status score in patients with acute myocardial infarction: comparison with the left ventricular ejection fraction and the exercise treadmill test performance. The MILIS Study Group. Am Heart J. 1991 May;121(5):1374-81. doi: 10.1016/0002-8703(91)90141-4.

  PMID: 2017970 BACKGROUND

• Tofler GH, Muller JE, Stone PH, Davies G, Davis VG, Braunwald E. Comparison of long-term outcome after acute myocardial infarction in patients never graduated from high school with that in more educated patients. Multicenter Investigation of the Limitation of Infarct Size (MILIS). Am J Cardiol. 1993 May 1;71(12):1031-5. doi: 10.1016/0002-9149(93)90568-w.

  PMID: 8475864 BACKGROUND

• Kloner RA, Muller J, Davis V. Effects of previous angina pectoris in patients with first acute myocardial infarction not receiving thrombolytics. MILIS Study Group. Multicenter Investigation of the Limitation of Infarct Size. Am J Cardiol. 1995 Mar 15;75(8):615-7. doi: 10.1016/s0002-9149(99)80628-6. No abstract available.

  PMID: 7887389 BACKGROUND

• Mullin SM, Warwick S, Akers M, Beecher P, Helminger K, Moses B, Rigby PA, Taplin NE, Werner W, Wettach R. An acute intervention trial: the research nurse coordinator's role. Control Clin Trials. 1984 Jun;5(2):141-56. doi: 10.1016/0197-2456(84)90120-x.

  PMID: 6744886 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Infarction; Myocardial Ischemia

Interventions

Propranolol; Hyaluronoglucosaminidase

Condition Hierarchy (Ancestors)

Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases

Study Officials

• Eugene Braunwald

  Harvard Medical School, Peter Bent Brigham Hospital

• Allan Jaffee

  Washington University School of Medicine

• James Willerson

  University of Texas

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: PREVENTION
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 27, 1999
• First Posted: October 28, 1999
• Study Start: September 1, 1977
• Study Completion: December 1, 1985
• Last Updated: July 12, 2016

Record last verified: 1985-12