Chronic Liver Disease
Conditions
Keywords
Methacetin, Breath, Test, Cirrhosis
Brief summary
This trial is a pivotal trial to validate the use of a 13 C labeled substrate called methacetin and the BreathID automatic breath testing system, for determination of cirrhosis in patients with chronic liver disease.
Detailed description
Patients with chronic liver disease who have a recent biopsy will be offered a breath test. Correlation will be shown between histology and breath test in determining cirrhosis.
Interventions
DEVICEc13 methacetin solution with breath analyzer
Carbon 13 methacetin 75mg dissolved in 150 ml is given to the subject and metabolism is measured by a breath analyzer after decomposed by the liver
Sponsors
Meridian Bioscience, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 with chronic liver disease
Exclusion criteria
* Patients that are taking hepatotoxin drug. * Patient with severe congestive heart failure * Patient with severe pulmonary hypertension * Patient with uncontrolled diabetes mellitus * Patient with previous surgical bypass surgery for morbid obesity * Patient with extensive small bowel resection * Patient currently receiving total parenteral nutrition * Patient is a recipients of any organ transplant * Patients that received any anti-viral treatment within the past year * Women who are pregnant * Patient allergic to acetaminophen (such as Tylenol or any other related medications) * Patient with history of chronic obstructive pulmonary disease or symptomatic bronchial asthma * Patients unable to sign informed consent * Patients that based on the opinion of the investigator should not be enrolled into this study * Patients that are participating in other clinical trials evaluating experimental treatments or procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Likelihood of Cirrhosis Based on Hepatic Impairment Score (HIS) | Study day 1 after a 1 hour test | Hepatic Impairment Score (HIS) is a score based on breath test parameters and demographic parameters of the subject being tested. A HIS value greater than 0.14 would mean that the subject is likely to be cirrhotic (based on biopsy result as the gold standard). The HIS is a probability score,i.e. ranges from 0 to 1, where 0 would mean the lowest probability of having liver cirrhosis and 1 would be the highest probability of having liver cirrhosis. This would be compared to the actual biopsy result of cirrhosis detection as the gold standard. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC of ROC (Area Under Receiver Operating Characteristic Curve) | At study day 1 after 1 hour test | The AUC represents a summary measure of the ROC curve and is the accuracy of the HIS in detecting cirrhosis compared to the gold standard of biopsy. |
Countries
Israel, United States
Participant flow
Recruitment details
414 subjects were collected in 11 sites; 8 in the United states and 3 in Israel. Recruitment began in August 2008 and was completed Sep 2009.
Pre-assignment details
4 sites, 1 in Israel and 3 in the United States recruited most of the subjects. Patients with chronic liver disease and recent biopsies performed or planned were approached. Exclusion criteria focused mostly on issues that would affect accuracy of breath test.
Participants by arm
| Arm | Count |
|---|---|
| CLD (Chronic Liver Disease) Chronic liver disease subjects with recent (within 3 months)liver biopsy will be tested with the 13C methacetin breath test, which entails connecting the subject via a nasal cannula to the BreathID analyzer and after measuring baseline breath, have the subject drink 150cc of aqueous solution which contains 75 mg of 13C -labeled methacetin (Intervention material) | 414 |
| Total | 414 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 13 |
Baseline characteristics
| Characteristic | CLD (Chronic Liver Disease) |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 39 Participants |
| Age, Categorical Between 18 and 65 years | 374 Participants |
| Age, Continuous | 51.3 years STANDARD_DEVIATION 10.9 |
| Region of Enrollment Israel | 87 participants |
| Region of Enrollment United States | 327 participants |
| Sex: Female, Male Female | 178 Participants |
| Sex: Female, Male Male | 236 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 414 |
| serious Total, serious adverse events | 0 / 414 |
Outcome results
Primary
Number of Subjects With Likelihood of Cirrhosis Based on Hepatic Impairment Score (HIS)
Hepatic Impairment Score (HIS) is a score based on breath test parameters and demographic parameters of the subject being tested. A HIS value greater than 0.14 would mean that the subject is likely to be cirrhotic (based on biopsy result as the gold standard). The HIS is a probability score,i.e. ranges from 0 to 1, where 0 would mean the lowest probability of having liver cirrhosis and 1 would be the highest probability of having liver cirrhosis. This would be compared to the actual biopsy result of cirrhosis detection as the gold standard.
Time frame: Study day 1 after a 1 hour test
Population: The primary efficacy was conducted on all evaluable subject data in the full analysis (FA)set with biopsy confirmed cirrhosis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CLD (Chronic Liver Disease) | Number of Subjects With Likelihood of Cirrhosis Based on Hepatic Impairment Score (HIS) | 146 Participants |
Comparison: The null hypothesis was sensitivity lower than 0.8. We assumed a sensitivity of 0.89 and required a power of 90% to test the hypothesis at a 5% level of significance, and calculated that 173 cirrhotic and 241 non-cirrhotic subjects were needed (for a one-sample binomial test of outcome versus constant).p-value: 0.092495% CI: [0.6607, 0.8809]Exact binomial test
Secondary
AUC of ROC (Area Under Receiver Operating Characteristic Curve)
The AUC represents a summary measure of the ROC curve and is the accuracy of the HIS in detecting cirrhosis compared to the gold standard of biopsy.
Time frame: At study day 1 after 1 hour test
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CLD (Chronic Liver Disease) | AUC of ROC (Area Under Receiver Operating Characteristic Curve) | 0.785 Probability |
p-value: <0.000195% CI: [0.737, 0.834]Regression, Logistic