Clinical Trial Results:
Clinical Study of the BreathID® LF System to train the algorithm for the ¹³C-Methacetin Breath Test (MBT) in assessment of Portal Hypertension in Patients with Compensated Liver Cirrhosis
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Summary
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EudraCT number |
2014-002037-59 |
Trial protocol |
ES |
Global end of trial date |
11 Jan 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
12 May 2021
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First version publication date |
12 May 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CSPH-EX-0414
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02143778 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Exalenz Bioscience
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Sponsor organisation address |
4 Hamaayan Street, Modiin, Israel, 7177872
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Public contact |
Avraham Hershkowitz, Exalenz Bioscience, 972 546605412, avrahamh@exalenz.com
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Scientific contact |
Avraham Hershkowitz, Exalenz Bioscience, 972 546605412, avrahamh@exalenz.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Mar 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
27 Oct 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Jan 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study is to develop an algorithm and its cut-off to detect CSPH, defined as HVPG ≥10mmHg, based on the MBT.
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Protection of trial subjects |
This test is a diagnostic test with 75mg of Methacetin (similar to paracetamol) used as as the testing substrate. No safety precautions were needed other than verifying that subject is not sensitive to paracetamol.
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Background therapy |
The gold standard for measuring portal hypertension in the liver is hepatic venous pressure gradient (HVPG). A measure of 12 or more mmHg is classified as severe portal hypertension (SPH). | ||
Evidence for comparator |
HVPG is standard of care in several countries for patients with cirrhotic livers. Several peer reviewed papers have been published on this subject as well. The proposed Methacetin Breath Test correlates to this invasive method in assessing the probability of SPH. | ||
Actual start date of recruitment |
01 Sep 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 158
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Country: Number of subjects enrolled |
United States: 39
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Country: Number of subjects enrolled |
France: 40
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Country: Number of subjects enrolled |
Switzerland: 9
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Worldwide total number of subjects |
246
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EEA total number of subjects |
198
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
161
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From 65 to 84 years |
85
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85 years and over |
0
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Recruitment
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Recruitment details |
At least 200 consecutive compensated cirrhotic patients , defined as cirrhotic patients without known liver decompensation complications and meeting all inclusion/exclusion criteria were to be enrolled on a walk-in basis of which at least 50 had to be positive for CSPH and at least 50 had to be negative for CSPH. | ||||||||||
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Pre-assignment
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Screening details |
3. Known chronic liver disease with cirrhosis confirmed by either: a. liver biopsy or b. clinical (palpable left lobe, splenomegaly) and laboratory (platelets <150,000/mm3 or albumin< 3.8g/dL, or INR >1.3) evidence of cirrhosis and/or c. imaging studies by abdominal sonography, computer assisted axial tomography, or magnetic resonance imaging, | ||||||||||
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Period 1
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Period 1 title |
Initial Visit (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Double blind | ||||||||||
Roles blinded |
Investigator, Subject | ||||||||||
Blinding implementation details |
Methacetin Breath Test results were withheld from investigator
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Arms
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Arm title
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General | ||||||||||
Arm description |
General walk- in population | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Methacetin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Single use bottle of solution to be administered orally by pouring into a cup, after 8 hour fasting.
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Baseline characteristics reporting groups
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Reporting group title |
Initial Visit
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
FA
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All subjects that were enrolled in this study will be included in this analysis
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End points reporting groups
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Reporting group title |
General
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Reporting group description |
General walk- in population | ||
Subject analysis set title |
FA
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects that were enrolled in this study will be included in this analysis
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End point title |
Clinically Significant Portal Hypertension [1] | |||||||||
End point description |
Methacetin Breath Test with a pre-defined cutoff was compared to HVPG for determination of clinically significant portal hypertension (CSPH) (defined as HVPG >10mmHg)
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End point type |
Primary
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End point timeframe |
One time diagnostic test for duration of 1 hour with 48 hour safety follow up
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was done for feasibility purposes only as a training trial for a validation trial design and study. No specific analyses were performed other the assessing area under the curve receiver operating curves, enabling validation protocol design. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Severe Portal Hypertension | |||||||||
End point description |
Methacetin Breath Test with pre determined cutoff compared to HVPG to determine severe portal hypertension (SPH) (defined as HVPG>12)
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End point type |
Secondary
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End point timeframe |
One time test with duration of 1 hour with a 48 hour safety follow up.
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
48 hours- from beginning of test that lasts 1 hour and a 48 hour follow up for possible safety issues.
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Assessment type |
Non-systematic | ||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
FA set
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Reporting group description |
The reporting will include the full analysis set | ||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0.5% | |||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
