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

• Status: Completed
• Trial end date: 2019-09-18
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Texas Southwestern Medical Center; William Lee
• Collaborators: Exalenz Bioscience LTD.; Medical University of South Carolina; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Michigan
• Treatments: Acetaminophen

Criteria

Inclusion Criteria:

1. Adult men or women (18-80 years of age)

2. Severe acute liver injury not related to acetaminophen overdose: INR ≥2.0; no evidence of HE

3. Acute liver failure: INR ≥1.5; presence of any degree of HE

4. Duration of illness <26 weeks

5. Enrolled into the ALFSG Registry.

6. Written informed consent from the patient or patient's legally authorized representative or family member as defined in the Federal Register Number 21 Congressional Federal Register (CFR)50.3(m)

Exclusion Criteria:

1. Evidence of pre-existing chronic liver disease

2. Pre-existing New York Heart Association stage III/IV heart failure

3. Evidence of pre-existing chronic renal failure

4. Chronic hemodialysis prior to hospital admission

5. Evidence of cirrhosis (unless clinically acute Wilson disease or autoimmune non-APAP ALI or ALF)

6. Severe obstructive lung disease (FEV1 <50% of predicted on previous spirometry)

7. Severe shock, defined as mean arterial pressure (MAP) <70 mmHg despite >15 µg/kg/min dopamine, >0.1 µg/kg/min epinephrine, or >0.1 norepinephrine µg/kg/min

8. Extensive small bowel resection (>50 cm)

9. Any evidence of upper GI bleeding at enrollment requiring intervention (endoscopy or red blood cell (RBC) transfusion specifically for upper GI bleeding)

10. Liver transplantation (LT) prior to enrollment. (Note: Listing for LT does not preclude participation in the trial.)

11. Pregnancy or breastfeeding women (Note: Pregnancy related non-APAP ALI or ALF may be considered for entry following the delivery of the baby and assuming the mother does not wish to breastfeed or collect breast milk during the study period.)

12. Allergic to acetaminophen (such as Tylenol® or any other acetaminophen-containing medications)

13. Participation in other clinical studies evaluating other experimental treatments or procedures. (Note: Participation in observatory studies is not an exclusion.)

14. Patients in whom enteral drugs or fluids are contra-indicated or the patient either does not have an appropriately placed naso-enteric/orogastric tube in situ or cannot tolerate taking the drug preparation orally (200 ml)

15. Budd-Chiari Syndrome

16. Non-APAP ALI or ALF caused by malignancy

17. Moderate and severe adult respiratory distress syndrome (ARDS), as defined by Berlin Criteria.

18. Subjects who have received amiodarone in the 30 days prior to study enrollment

19. Consumption of any food or beverage that contains caffeine in the 24 hours prior to enrollment

20. Consumption of any of the following drugs that may interfere with the metabolism of 13C-Methacetin in the 48 hours prior to study enrollment including: allopurinol, carbamazepine, cimetidine, ciprofloxacin, daidzein, disulfiram, Echinacea, enoxacin, fluvoxamine, methoxsalen, mexiletine, montelukast, norfloxacin, phenylpropanolamine, phenytoin, propafenone, rifampin, terbinafine, ticlopidine, thiabendazole, verapamil, zileuton or oral contraceptives

21. Consumption of alcohol in the 24 hours prior to enrollment

22. Smoking cigarettes in the 8 hours prior to enrollment.