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

The ALF-MBT protocol is for a multicenter, open label, non-randomized study to determine the
value of Breath Identification® (BreathID®) Acute Liver Failure 13C-Methacetin Breath Test
System in predicting the outcome of patients diagnosed with 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 on all patients 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.

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.

Eligibility Criteria

Inclusion Criteria:

1. Adult men or women (18-70 years of age)

2. Severe acute liver injury

3. INR ≥1.5

4. Presence of any degree of hepatic encephalopathy

5. Duration of illness <26 weeks

6. Enrolled into the ALFSG Registry.

7. Written informed consent from the patient or patient's legally authorized
representative or family member as defined in the Federal Register Number
21CFR50.3(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 for ALF

5. Evidence of cirrhosis (unless clinically acute Wilson disease or autoimmune 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

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 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 (i.e., enrollment in the ornithine phenyl acetate (OPA) Study (called
STOP-ALF) precludes enrollment in ALF-MBT Study) (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/orogastric tube in situ or cannot tolerate
taking the drug preparation orally (200 ml)

15. ALF due to Budd-Chiari Syndrome

16. ALF caused by malignancy

17. ALF caused by known or suspected herpes simplex virus requiring acyclovir therapy

18. Moderate and severe adult respiratory distress syndrome (ARDS), as defined by Berlin
Criteria ALF-MBT manual of procedures (MOP).

19. Subjects who have received amiodarone or a 3-hydroxy-3-methyl-glutaryl (HMG)-Coenzyme
A (CoA) reductase (Statin) drug in the 30 days prior to study enrollment

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

21. 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: Acyclovir,
allopurinol, carbamazepine, cimetidine, ciprofloxacin, daidzein, disulfiram,
Echinacea, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, montelukast,
norfloxacin, phenylpropanolamine, phenytoin, propafenone, rifampin, terbinafine,
ticlopidine, thiabendazole, verapamil, zileuton or oral contraceptives

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

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

Principal Investigator

Jody C. Olson, MD

Study Contact

Jody C. Olson, MD, jolson2@kumc.edu, 913-588-1591

Estimated Completion Date

Saturday, August 1, 2020

ClinicalTrials.gov #

NCT02786836
05/31/2016