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Eligibility
for people ages 18–70
Location
at San Francisco, California and other locations
Dates
study started
estimated completion:
Principal Investigator

Description

Summary

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.

Official Title

13C-Methacetin Breath Test for the Prediction of Outcome in Acute Liver Failure

Details

The importance of identifying the patient with ALF who is likely to die without a liver transplant cannot be overstated and has remained a primary focus of clinical investigation for 25 years. Traditional scoring systems and prognostic models, such as King's College Criteria (KCC), Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II), currently used to monitor patients with ALF lack individual sensitivity and specificity and do not provide direct information about the liver's metabolic function, which is a key variable in assessing liver status and potential disease progression versus recovery in ALF patients. Despite recent advances used by the ALFSG Prognostic Index (ALFSG-PI) and Model for End-Stage Liver Disease (MELD), better predictive modalities are still needed.

The 13C-Methacetin breath test is a rapid, reproducible, point-of-care test of liver metabolic function. After oral or nasogastric tube administration, the 13C labeled Methacetin is O-demethylated by cytochrome P4501A2 in the liver and further biotransformed into 13CO2, which is expired in breath. The BreathID® MCS device captures and quantifies expired 13CO2 and standardizes recovery against expired 12CO2 through a nasal cannula (in conscious patients) or an adaptor connected to the ventilator line (for intubated patients). The results obtained from the device are expressed as delta over baseline (DOB), which expresses the change in 13CO2/12CO2 ratio in comparison to the baseline measurement. It can be transformed into the percentage of 13C dose recovered over time (PDR) after the ingestion of Methacetin, and the cumulative PDR (CPRD), the rate at which 13C substrate is metabolized, derived from the breath 13C/12C ratio.

This is a multicenter, open label, non-randomized study of the ALF-MBT to assess functional trends of liver metabolism in patients diagnosed with ALF. Up to 200 evaluable male and female patients with acute liver failure present at the time of enrollment into the ALFSG Registry will be consecutively enrolled. An evaluable patient is one who has completed one or more ALF-MBTs measured for a minimum of 30 (and ideally 60) minutes after administration of 13C-Methacetin. Study sites will include up to 12 of the clinical sites located in the United States that are involved in the Acute Liver Failure Study Group.

The ALF-MBT will be performed on all patients upon admission into the study (Day 1) and repeated on Days 2, 3, 5 and 7, as close to the same time of day as possible (within ± 4 hours), provided no contra-indications are present. Subjects will be contacted for the Day 21 follow up (21 days after the subject's enrollment into the trial) to determine spontaneous survival, transplantation and occurrence of serious adverse events since the subject's last study treatment.

Keywords

Acute Liver Failure methacetin breath test severe acute liver injury hepatic encephalopathy ALFSG Registry acetaminophen toxicity Acetaminophen

Eligibility

You can join if…

Open to people ages 18–70

  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)

You CAN'T join if...

  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.)

  1. 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)
  2. ALF due to Budd-Chiari Syndrome
  3. ALF caused by malignancy
  4. ALF caused by known or suspected herpes simplex virus requiring acyclovir therapy
  5. Moderate and severe adult respiratory distress syndrome (ARDS), as defined by Berlin Criteria ALF-MBT manual of procedures (MOP).
  6. 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
  7. Consumption of any food or beverage that contains caffeine in the 24 hours prior to enrollment
  8. 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
  9. Consumption of alcohol in the 24 hours prior to enrollment
  10. Smoking cigarettes in the 8 hours prior to enrollment.

Locations

  • University of Washington Medical Center not yet accepting patients
    Seattle, Washington, 98195, United States
  • UT Southwestern Medical Center at Dallas accepting new patients
    Dallas, Texas, 75390-8887, United States
  • University of Kansas Medical Center not yet accepting patients
    Kansas City, Kansas, 66160, United States
  • Northwestern University accepting new patients
    Chicago, Illinois, 60611, United States
  • University of Alabama, Birmingham not yet accepting patients
    Birmingham, Alabama, 35294, United States
  • University of Michigan not yet accepting patients
    Ann Arbor, Michigan, 48109, United States
  • Ohio State University Medical Center accepting new patients
    Columbus, Ohio, 43210, United States
  • Emory University Hospital not yet accepting patients
    Atlanta, Georgia, 30322, United States
  • Medical University of South Carolina not yet accepting patients
    Charleston, South Carolina, 29425, United States
  • VCU Medical Center accepting new patients
    Richmond, Virginia, 23298, United States
  • Yale University School of Medicine not yet accepting patients
    New Haven, Connecticut, 06520, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
William Lee
Links
Acute Liver Failure Study Website
ID
NCT02786836
Phase
Phase 2/3
Lead Scientist
Bilal Hameed
Study Type
Interventional
Last Updated
June 2016
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