Clinical Trial Results:
Brain muscle axis during treatment of hepatic encephalopathy with L-ornithine L-aspartate
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Summary
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EudraCT number |
2012-003817-32 |
Trial protocol |
GB |
Global end of trial date |
19 Jun 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Jul 2020
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First version publication date |
30 Jul 2020
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Other versions |
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Summary report(s) |
LOLA results presented in ISHEN 2016 and published in J HEP |
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 |
LOLA-Merz:WMDHP39937
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01847651 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Imperial College London
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Sponsor organisation address |
South Wharf Road, London, United Kingdom,
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Public contact |
Dr Yasmin Pasha, Imperial College London, +44 02078866454, y.pasha@imperial.ac.uk
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Scientific contact |
Professor Simon Taylor-Robinson, Imperial College London, +44 02078866454, s.taylor-robinson@imperial.ac.uk
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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 |
28 Oct 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Jun 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Jun 2015
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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 |
Primary objective: Improvement in mental state by paper-and-pencil-based Psychometric Hepatic Encephalopathy Score (PHES) and Cogstate Research test(computer-based cognitive assessment research tool)
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Protection of trial subjects |
Initial REC recommendation was to exclude subjects with renal impairment from screening, the Patient consent form reflects this. A metal safety questionnaire was carried out at screening visit and each study visit and signed afresh prior to each MRI scan.
Prior to each study visit the subjects underwent consent for ongoing trial participation muscle biopsies and scans. I regularly screened for side effects and effects. I also gave my contact details and email which was checked daily for either any complications of study procedures ie muscle biopsy. The contact details for the nursing staff at the liver day unit were also provided, these staff knew the study protocol and had access to my mobile number even out of hours, in case of an emergency. I asked nurses on liver day unit to collect written feedback questionnaires post muscle biopsy.
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Background therapy |
Those already on lactulose could remain on it however during the study period. However subjects could not go on lactulose during 12 week study period, if not on it at study start but they were free to do so afterwards. If a subject received a liver transplant or antibiotics (unless taken for unrelated condition) or experienced a GI Bleed during this 12 weeks their data would also be excluded. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Aug 2013
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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 |
United Kingdom: 34
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Worldwide total number of subjects |
34
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EEA total number of subjects |
34
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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) |
34
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Study powered at n=34. Recruitment occurred from screened patients who gave their consent at St Mary's Hospital Cirrhosis Clinic. The screening began in May 2013. The first patient first visit occurred on 23/08/2013 and the last patient's last visit occurred on 19/06/2015. | |||||||||
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Pre-assignment
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Screening details |
I performed all screening visits and recruitment in accordance with inclusion and exclusion criteria. 102 patients were screened. 69 met criteria (33 did not) and consented for screening. | |||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||
Blinding implementation details |
Envelopes containing unblinding information for each pharmacy pack number for unblinding were kept in Imperial Research Pharmacy. These were not accessed until after data collection and subject participation was complete
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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L-ORNITHINE L-ASPARTATE (LOLA) | |||||||||
Arm description |
LOLA taken at 6g tds for 12 weeks total | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
L-ornithine-L aspartate
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Investigational medicinal product code |
LOLA
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Other name |
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Pharmaceutical forms |
Effervescent granules for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
6g orally three times a day, 2 sachets to be dissolved fully in 1 cup cold water or cordial taken three times a day
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Arm title
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Placebo | |||||||||
Arm description |
Identical orange flavour granules to IMP were prepared and suplliedin identical packaging by Merz Phramceuticals | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Dummy LOLA/Placebo
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Investigational medicinal product code |
LOLA
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Other name |
Placebo
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Pharmaceutical forms |
Effervescent granules for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
6g orally three times a day, 2 sachet to be dissolved fully in 1 cup cold water or cordial taken three times a day
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Baseline characteristics reporting groups
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Reporting group title |
L-ORNITHINE L-ASPARTATE (LOLA)
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Reporting group description |
LOLA taken at 6g tds for 12 weeks total | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Identical orange flavour granules to IMP were prepared and suplliedin identical packaging by Merz Phramceuticals | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
baseline differences between groups
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
34 Subjects completed the trial. After unblinding 14 were in Treatment Arm and 20 in the Placebo group.
There were no significant baseline differences between groups at the outset
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End points reporting groups
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Reporting group title |
L-ORNITHINE L-ASPARTATE (LOLA)
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Reporting group description |
LOLA taken at 6g tds for 12 weeks total | ||
Reporting group title |
Placebo
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Reporting group description |
Identical orange flavour granules to IMP were prepared and suplliedin identical packaging by Merz Phramceuticals | ||
Subject analysis set title |
baseline differences between groups
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
34 Subjects completed the trial. After unblinding 14 were in Treatment Arm and 20 in the Placebo group.
There were no significant baseline differences between groups at the outset
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End point title |
Better concentration [1] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
measured at 0, 4 and 12 weeks
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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: Unknown |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Better memory [2] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
measured at 0, 4 and 12 weeks
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| Notes [2] - 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: Unknown |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Better quality sleep [3] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Measured at 0, 4 and 12 weeks
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| Notes [3] - 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: Unknown |
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| No statistical analyses for this end point | ||||||||||
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End point title |
More stamina/strength [4] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Measured at 0, 4 and 12 weeks
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| Notes [4] - 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: Unknown |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Less irritable [5] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Measured at 0, 4 and 12 weeks
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| Notes [5] - 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: Unknown |
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| No statistical analyses for this end point | ||||||||||
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End point title |
More energy [6] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Measured at 0, 4 and 12 weeks
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| Notes [6] - 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: Unknown |
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| No statistical analyses for this end point | ||||||||||
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End point title |
More rested [7] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Measured at 0, 4 and 12 weeks
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| Notes [7] - 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: Unknown |
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| No statistical analyses for this end point | ||||||||||
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End point title |
No different [8] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Measured at 0, 4 and 12 weeks
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| Notes [8] - 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: Unknown |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
12 weeks
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Adverse event reporting additional description |
3 subjects in placebo arm were hospitalised following randomisation, 1 for dehydration, one for unrelated orthopaedic fracture, 1 for an unrelated hernia repair surgery. Protocol deemed all hospital admssions to be SAEs
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
SAE form completed | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
LOLA
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Reporting group description |
Active treatment arm. LOLA taken at 6g tds for 12 weeks total | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: only 3 SAEs recorded in placebo arm of this study |
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 | |||
