13C-Methacetin Breath Test for the Prediction of Outcome in in ALI or ALF

Summary

The ALFSG-MBT protocol is for a multicenter, open label, non-randomized study to determine the value of Breath Identification® (BreathID®) N-(4-Methoxy-13C-phenyl)acetamide (13C-Methacetin) Breath Test System in predicting the outcome of patients diagnosed with severe acute liver injury that is not related to acetaminophen overdose or acute liver failure who meet inclusion/exclusion criteria. Up to 200 evaluable patients will be enrolled. An evaluable patient is one who has completed one or more breath tests for at least 30 minutes after administration of the 13C-Methacetin solution (test substrate). The Breath Test will be performed up to five times during the study period on all enrolled patients. The first Breath Test will be performed upon admission into the study (Day 1) and repeated on Days 2, 3, 5 and 7 provided no contra-indications are present. Each test continuously measures changes in the metabolism of the 13C-Methacetin in order to assess the improvement or deterioration in liver metabolic function about improvement or deterioration in liver metabolic function. If an enrolled non-APAP ALI or ALF patient receives a liver transplant, is discharged /transferred from the hospital or dies prior to Day 7, additional Breath Tests will not be performed. Patients will be contacted for the Day 21 follow up (21 days after enrollment into the trial) to determine spontaneous survival, transplantation and occurrence of serious adverse events since the patient's last study treatment.

Timeline

Start

2016-06-10

Primary completion

2019-09-18

Completion

2019-09-18

Publications

• Background O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989 Aug;97(2):439-45. doi: 10.1016/0016-5085(89)90081-4.
• Background Cholongitas E, Senzolo M, Patch D, Kwong K, Nikolopoulou V, Leandro G, Shaw S, Burroughs AK. Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit. Aliment Pharmacol Ther. 2006 Apr 1;23(7):883-93. doi: 10.1111/j.1365-2036.2006.02842.x.
• Background Craig DG, Ford AC, Hayes PC, Simpson KJ. Systematic review: prognostic tests of paracetamol-induced acute liver failure. Aliment Pharmacol Ther. 2010 May;31(10):1064-76. doi: 10.1111/j.1365-2036.2010.04279.x. Epub 2010 Feb 24.
• Background Stravitz RT, Reuben A, Mizrahi M, Lalazar G, Brown K, Gordon SC, Ilan Y, Sanyal A. Use of the methacetin breath test to classify the risk of cirrhotic complications and mortality in patients evaluated/listed for liver transplantation. J Hepatol. 2015 Dec;63(6):1345-51. doi: 10.1016/j.jhep.2015.07.021. Epub 2015 Jul 26.
• Background Lalazar G, Adar T, Ilan Y. Point-of-care continuous (13)C-methacetin breath test improves decision making in acute liver disease: results of a pilot clinical trial. World J Gastroenterol. 2009 Feb 28;15(8):966-72. doi: 10.3748/wjg.15.966.
• Background Goetze O, Selzner N, Fruehauf H, Fried M, Gerlach T, Mullhaupt B. 13C-methacetin breath test as a quantitative liver function test in patients with chronic hepatitis C infection: continuous automatic molecular correlation spectroscopy compared to isotopic ratio mass spectrometry. Aliment Pharmacol Ther. 2007 Jul 15;26(2):305-11. doi: 10.1111/j.1365-2036.2007.03360.x.
• Background Nista EC, Fini L, Armuzzi A, Candelli M, Zocco MA, Cazzato IA, Merra G, Finizio R, Miele L, Grieco A, Gasbarrini G, Gasbarrini A. 13C-breath tests in the study of microsomal liver function. Eur Rev Med Pharmacol Sci. 2004 Jan-Feb;8(1):33-46.
• Background Starmer GA, McLean S, Thomas J. Analgesic potency and acute toxicity of substituted anilides and benzamides. Toxicol Appl Pharmacol. 1971 May;19(1):20-8. doi: 10.1016/0041-008x(71)90185-2. No abstract available.
• Background de Franchis R. Updating consensus in portal hypertension: report of the Baveno III Consensus Workshop on definitions, methodology and therapeutic strategies in portal hypertension. J Hepatol. 2000 Nov;33(5):846-52. doi: 10.1016/s0168-8278(00)80320-7. No abstract available.
• Background Lalazar G, Pappo O, Hershcovici T, Hadjaj T, Shubi M, Ohana H, Hemed N, Ilan Y. A continuous 13C methacetin breath test for noninvasive assessment of intrahepatic inflammation and fibrosis in patients with chronic HCV infection and normal ALT. J Viral Hepat. 2008 Oct;15(10):716-28. doi: 10.1111/j.1365-2893.2008.01007.x. Epub 2008 Jul 11.
• Background Lalazar G, Mullhaupt, B., Margalit M. Point of care non-invasive 13C methacetin breath testing accurately identifies significant liver inflammation and fibrosis: a novel method for assessing liver damage. Gastroenterology; 2007 abstract
• Background Allman K, Wilson I. Oxford Handbook of Anaesthesia. 2nd ed. New York: Oxford University Press 2006;xxiv:1203.
• Background Lee WM, James L, Wendon J, Stravitz RT, Pop OT, Audimoolam VK. Does Methacetin breath testing increase acetaminophen hepatotoxicity in the setting of acute liver failure? Hepatology 2015: Accepted for poster presentation at the AASLD Liver Meeting held in San Francisco from November 13-17, 2015.
• Background Audimoolam VK, Patel VC, Bernal W, Meir M, Lalazar G, Ilan Y, Wendon J. Use of an on-line at the point of care 13C-methacetin breath test as an adjunct tool for decision making in patients with acute liver failure. Hepatology 56;4Suppl:970A.
• Background Koch DG, Battenhouse H, Durkalski V, Lee WM, Reuben A. Clinical predictors of spontaneous survival in acute liver failure (ALF) patients with advanced coma. Hepatology 56;4Suppl:964A.
• Background Koch DG, Speiser JL, Durkalski V, Fontana RJ, Davern T, McGuire B, Stravitz RT, Larson AM, Liou I, Fix O, Schilsky ML, McCashland T, Hay JE, Murray N, Shaikh OS, Ganger D, Zaman A, Han SB, Chung RT, Brown RS, Munoz S, Reddy KR, Rossaro L, Satyanarayana R, Hanje AJ, Olson J, Subramanian RM, Karvellas C, Hameed B, Sherker AH, Lee WM, Reuben A. The Natural History of Severe Acute Liver Injury. Am J Gastroenterol. 2017 Sep;112(9):1389-1396. doi: 10.1038/ajg.2017.98. Epub 2017 Apr 25.
• Stravitz RT, Fontana RJ, Karvellas C, Durkalski V, McGuire B, Rule JA, Tujios S, Lee WM; Acute Liver Failure Study Group. Future directions in acute liver failure. Hepatology. 2023 Oct 1;78(4):1266-1289. doi: 10.1097/HEP.0000000000000458. Epub 2023 May 16.

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