Clinical Trial Results:
Effects of plasma exchange on the serum albumin functional capacity, circulatory dysfunction, renal and cerebral function in cirrhotic subjects with acute-on-chronic liver failure
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Summary
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EudraCT number |
2010-021360-15 |
Trial protocol |
ES |
Global end of trial date |
17 Sep 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Aug 2019
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First version publication date |
11 Aug 2019
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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 |
IG0905
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01201720 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Instituto Grifols, S.A.
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Sponsor organisation address |
Can Guasch 2, Parets del Valles, Barcelona, Spain, 08150
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Public contact |
Mireia Torres, MSc, Instituto Grifols S.A., mireia.torres@grifols.com
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Scientific contact |
Mireia Torres, MSc, Instituto Grifols S.A., mireia.torres@grifols.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 |
24 May 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Sep 2013
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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 was to assess the effects of plasma exchange (PE) with albumin 5% as a replacement fluid on the albumin functional capacity and circulatory dysfunction in cirrhotic subjects with acute-on-chronic liver failure (ACLF).
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Protection of trial subjects |
Standards for Good Clinical Practice were adhered to for all procedures in this clinical study. The investigators ensured that the clinical study was conducted in full conformance with appropriate local laws and regulations and the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Mar 2011
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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: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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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) |
9
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Ten subjects with liver cirrhosis established by biopsy or clinical, laboratory, and ultrasound data and ACLF determined as an acute deterioration in liver function occurring in 2 to 4 weeks with jaundice and hepatic encephalopathy (HE) and/or renal insufficiency were enrolled from March 2011 to July 2013 in this single-center study. | ||||||||||||
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Pre-assignment
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Screening details |
Subjects with liver cirrhosis and ACLF admitted to the study center, who gave their written informed consent to participate, were included in the study. In the case of HE, written informed consent was given by a first-degree relative of the subject. Subjects underwent various clinical tests to check their suitability to participate in the study. | ||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
This was an open-label study; no blinding techniques were applicable.
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Arms
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Arm title
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Enrolled Population | ||||||||||||
Arm description |
All Subjects were included in the Enrolled population. The Enrolled population was defined as all subjects who met the inclusion criteria and performed at least one PE with albumin 5%. The Enrolled population was used for safety analysis. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Albutein (Human Albumin Grifols 5% solution for infusion)
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Investigational medicinal product code |
B05AA01
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The volume of each replacement was approximately that of the plasma volume of the subjects as calculated from body weight, height, and hematocrit (approximately 35 to 45 mL/kg, corresponding to a volume of 2500 to 3000 mL).
Plasma exchange (PE) was performed every 2 days over 11 days, for a total of 6 PEs. Additionally, fresh frozen plasma (FFP) was administered at the end of each plasma exchange session (~30% of total plasma exchanged).
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
A total of 10 subjects were included in the Enrolled population and treated with the study drug. The Enrolled population was defined as all subjects who met the inclusion criteria and performed at least one PE with albumin 5%. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Enrolled Population
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Reporting group description |
All Subjects were included in the Enrolled population. The Enrolled population was defined as all subjects who met the inclusion criteria and performed at least one PE with albumin 5%. The Enrolled population was used for safety analysis. | ||
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End point title |
Albumin Functional Capacity [1] | ||||||||||||||||||||||||||||||||||||
End point description |
Changes in albumin functional capacity within Day 1 (first PE) and last PE (whichever day this occurred) measured using 3 techniques: albumin binding capacity (ABiC), Electronic Paramagnetic Resonance (EPR), and albumin redox state.
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End point type |
Primary
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End point timeframe |
Day 1 (first assessment) to Day 10 or 11 (last assessment)
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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: As this study was not controlled, no statistical analysis can be drawn as a comparator. Only one study arm exists. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Circulatory Dysfunction [2] | ||||||||||||||||||||
End point description |
Changes in circulatory dysfunction throughout the study.
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End point type |
Primary
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End point timeframe |
Day 1 (first assessment) to Day 11 (last assessment)
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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: As this study was not controlled, no statistical analysis can be drawn as a comparator. Only one study arm exists. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Renal Dysfunction | ||||||||||||
End point description |
Change in Renal dysfunction throughout the study.
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End point type |
Secondary
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End point timeframe |
Pre-PE, Day 1 (first assessment) to Month 1 (last assessment)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Cerebral Dysfunction | ||||||||
End point description |
Change in cerebral dysfunction measured by the grade of encephalopathy throughout the study.
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End point type |
Secondary
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End point timeframe |
Pre-PE, Day 1 (first assessment) to Month 1 (last assessment)
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| No statistical analyses for this end point | |||||||||
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End point title |
Liver Function | ||||||||||||||||||||||||
End point description |
Change in liver function throughout the study.
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End point type |
Secondary
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End point timeframe |
Pre-PE, Day 1 (first assessment) to Month 1 (last assessment) for all parameters except Score prognostics (Day 1 to Day 10)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Systemic Inflammation | ||||||||||||||
End point description |
Change in systemic inflammation throughout the study.
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End point type |
Secondary
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End point timeframe |
Pre-PE, Baseline (first assessment) to Day 11 (last assessment) for aldosterone.
Pre-PE, Day 1 (first assessment) to Day 10 (last assessment) for vW:Ag and vW:RCo
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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 |
Adverse events were collected from the time of signature of the ICF to Day 11.
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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 |
17.1
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Reporting groups
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Reporting group title |
Enrolled population
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Reporting group description |
The Enrolled population was defined as all subjects who met the inclusion criteria and performed at least one PE with albumin 5%. The Enrolled population was used for safety analysis. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Feb 2012 |
The aim of the amendment was to modify the number of subjects to be included in the study. The initial number of subjects planned was 10 in total, without taking into account the number of PE received.
At the beginning of the study, there were some subject early discontinuations which corresponded to several causes, including severity of underlying subject pathologies, inclusion/exclusion criteria
violations, possibility of study withdrawal due to liver transplantation, etc. Therefore, it was considered appropriate to specify that it was necessary to obtain 10 subjects who had completed the 6 PE planned in the protocol. |
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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 | |||
