Clinical Trial Results:
An international, multicenter, randomized controlled clinical trial assessing the efficacy of Ursodeoxycholic acid as a volume reducing treatment for symptomatic polycystic livers
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Summary
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EudraCT number |
2013-003207-19 |
Trial protocol |
NL ES |
Global end of trial date |
16 Feb 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
11 May 2021
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First version publication date |
11 May 2021
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Other versions |
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Summary report(s) |
Journal article UDCA for PLD JHEP 2016 |
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 |
PLD11-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02021110 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Radboudumc
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Sponsor organisation address |
Geert Grooteplein Zuid, Nijmegen, Netherlands, 6525GA
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Public contact |
Dep.of Gastroenterology&Hepatology, Radboud University Nijmegen Medical Center, 0031 0243619190, joostphdrenth@cs.com
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Scientific contact |
Dep.of Gastroenterology&Hepatology, Radboud University Nijmegen Medical Center, 0031 0243619190, joostphdrenth@cs.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 |
16 Feb 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Feb 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Feb 2016
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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 |
First, to demonstrate whether UDCA-therapy is effective in reducing total liver volume in PLD patients.
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Protection of trial subjects |
data safety monitoring board was involved
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Oct 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 |
Netherlands: 30
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Country: Number of subjects enrolled |
Spain: 4
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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) |
28
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From 65 to 84 years |
6
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85 years and over |
0
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Recruitment
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Recruitment details |
Inclusion period: May 2015 untill February 2015 | |||||||||
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Pre-assignment
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Screening details |
38 patients were screened for eligibility and 34 patients were randomized. All patients completed the total follow-up of 36 weeks by November 2015. | |||||||||
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Period 1
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Period 1 title |
Baseline period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
not blinded study
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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UDCA | |||||||||
Arm description |
Eligible patients were randomly assigned in blocks of four in a 1:1 ratio to receive UDCA (Ursochol, Zambon, the Netherlands), orally twice a day, in a dose of 15–20 mg/kg/day for 24 weeks. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
ursodeoxycholic acid
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
15–20 mg/kg/day
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Arm title
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Control group | |||||||||
Arm description |
Underwent follow-up without any clinical trial treatment. | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
UDCA
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Reporting group description |
Eligible patients were randomly assigned in blocks of four in a 1:1 ratio to receive UDCA (Ursochol, Zambon, the Netherlands), orally twice a day, in a dose of 15–20 mg/kg/day for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
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Reporting group description |
Underwent follow-up without any clinical trial treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
UDCA
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Reporting group description |
Eligible patients were randomly assigned in blocks of four in a 1:1 ratio to receive UDCA (Ursochol, Zambon, the Netherlands), orally twice a day, in a dose of 15–20 mg/kg/day for 24 weeks. | ||
Reporting group title |
Control group
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Reporting group description |
Underwent follow-up without any clinical trial treatment. | ||
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End point title |
Proportional change in liver volume | |||||||||
End point description |
The main outcome measure will be the proportional change of total liver volume from baseline to 6 months as determined by CT.
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End point type |
Primary
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End point timeframe |
Assessment of end point: February 2015
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Statistical analysis title |
Statistical analysis | |||||||||
Statistical analysis description |
Continuous variables were expressed as mean (95% confidence interval (CI)) if normally distributed, otherwise as median (interquartile range (IQR)). Primary
outcome and secondary outcomes on TLV, TKV, HRQL and symptoms, were tested with independent t-tests between groups and paired sampled t tests comparing baseline and end of study within groups.
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Comparison groups |
UDCA v Control group
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Number of subjects included in analysis |
32
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
P-value |
< 0.05 [2] | |||||||||
Method |
proportional change TLV | |||||||||
Parameter type |
proportional change TLV | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.3 | |||||||||
upper limit |
8.8 | |||||||||
Variability estimate |
Standard deviation
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| Notes [1] - Primary outcome of this trial was proportional change in TLV from baseline to week 24 between UDCA group and control group. [2] - p |
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Adverse events information
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Timeframe for reporting adverse events |
From May 2014 (first baseline) untill Oktober 2015 (last follow-up visit T3 )
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Adverse event reporting additional description |
Every visit patients were asked about adverse events which were documented in a table. Supplementary Table 4 in the paper contains all information about adverse events.
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Assessment type |
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 |
Adverse events UDCA
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Reporting group description |
A total of 15 (94%) participants in the UDCA group and 12 (71%) in the control group had at least one adverse event (p = 0.085) (Supplementary Table 3). Most common adverse events in the UDCA group compared to the control group were frequent stools or diarrhea (38% vs. 12%, p = 0.017) probably related to the study drug. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Adverse events control group
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Reporting group description |
A total of 15 (94%) participants in the UDCA group and 12 (71%) in the control group had at least one adverse event (p = 0.085) (Supplementary Table 3). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
| see JHEP article | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/27212247 |
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