Clinical Trial Results:
The use of Low Molecular Weight Heparin during Hemodiafiltration, A Cross Over Randomised Trial
Summary
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EudraCT number |
2008-005224-91 |
Trial protocol |
BE |
Global end of trial date |
15 May 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Oct 2020
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First version publication date |
07 Oct 2020
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Other versions |
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 |
AGO/2008/010
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00756145 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Ghent University Hospital
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Sponsor organisation address |
C. Heymanslaan 10, Ghent, Belgium, 9000
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Public contact |
HIRUZ CTU, Ghent University Hospital, 32 93320500, HIRUZ.ctu@uzgent.be
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Scientific contact |
HIRUZ CTU, Ghent University Hospital, 32 93320500, HIRUZ.ctu@uzgent.be
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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 |
02 Feb 2015
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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 |
15 May 2018
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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 aim of this study was to determine the optimal mode (place and time) of tinzaparin administration during postdilution hemodiafiltration.
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Protection of trial subjects |
Ethics review and approval, informed consent, supportive care and routine monitoring.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Sep 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Belgium: 14
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Worldwide total number of subjects |
14
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EEA total number of subjects |
14
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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) |
3
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From 65 to 84 years |
10
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85 years and over |
1
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Recruitment
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Recruitment details |
22 patients were screened in the period from 18-Sep-2008 till 02-Mar-2010. 14 patients were included and randomized. 1 patient was excluded from the study due to infection. End of trial notification was dated 02-Mar-2010 (last patient last visit) and submitted to EC and CA 24-Jul-2018. | |||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Inclusion criteria -age > 18 years - Chronic kidney disease (CKD) stadium 5 requiring chronic hemodiafiltration of hemodialysis - haematocrit > 30% - signed informed consent | |||||||||||||||||||||||||||||||||||
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 |
Not blinded | |||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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IN0-OUT0-IN5 | |||||||||||||||||||||||||||||||||||
Arm description |
Administration of tinzaparin in this arm the first week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0), the second week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the third week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
tinzaparin
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Investigational medicinal product code |
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Other name |
Innohep, Leo Pharmaceutical Corp, Ballerup, Denmark
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Haemodialysis
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Dosage and administration details |
Tinzaparin with median and interquartile range of 4500 (3500–4500) IU was routinely used. Before the study, tinzaparin was injected in the afferent blood line shortly after the start of the session. The doses had been defined prior to the start of the study, based on the presence or absence of visible clotting of membrane and circuit and/or prolonged bleeding after dialysis.
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Arm title
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IN0-IN5-OUT0 | |||||||||||||||||||||||||||||||||||
Arm description |
Administration of tinzaparin in this arm the first week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0), the second week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the third week: administration at the outlet blood line just prior the start of the blood pump (OUT0) | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
tinzaparin
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Investigational medicinal product code |
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Other name |
Innohep, Leo Pharmaceutical Corp, Ballerup, Denmark
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Haemodialysis
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Dosage and administration details |
Tinzaparin with median and interquartile range of 4500 (3500–4500) IU was routinely used. Before the study, tinzaparin was injected in the afferent blood line shortly after the start of the session. The doses had been defined prior to the start of the study, based on the presence or absence of visible clotting of membrane and circuit and/or prolonged bleeding after dialysis.
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Arm title
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OUT0-IN5-IN0 | |||||||||||||||||||||||||||||||||||
Arm description |
Administration of tinzaparin in this arm the first week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the second week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the third week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
tinzaparin
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Investigational medicinal product code |
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Other name |
Innohep, Leo Pharmaceutical Corp, Ballerup, Denmark
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Haemodialysis
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Dosage and administration details |
Tinzaparin with median and interquartile range of 4500 (3500–4500) IU was routinely used. Before the study, tinzaparin was injected in the afferent blood line shortly after the start of the session. The doses had been defined prior to the start of the study, based on the presence or absence of visible clotting of membrane and circuit and/or prolonged bleeding after dialysis.
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Arm title
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OUT0-IN0-IN5 | |||||||||||||||||||||||||||||||||||
Arm description |
Administration of tinzaparin in this arm the first week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the second week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) the third week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
tinzaparin
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Investigational medicinal product code |
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Other name |
Innohep, Leo Pharmaceutical Corp, Ballerup, Denmark
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Haemodialysis
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Dosage and administration details |
Tinzaparin with median and interquartile range of 4500 (3500–4500) IU was routinely used. Before the study, tinzaparin was injected in the afferent blood line shortly after the start of the session. The doses had been defined prior to the start of the study, based on the presence or absence of visible clotting of membrane and circuit and/or prolonged bleeding after dialysis.
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Arm title
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IN5-IN0-OUT0 | |||||||||||||||||||||||||||||||||||
Arm description |
Administration of tinzaparin in this arm the first week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the second week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) the third week: administration at the outlet blood line just prior the start of the blood pump (OUT0) | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
tinzaparin
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Investigational medicinal product code |
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Other name |
Innohep, Leo Pharmaceutical Corp, Ballerup, Denmark
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Haemodialysis
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Dosage and administration details |
Tinzaparin with median and interquartile range of 4500 (3500–4500) IU was routinely used. Before the study, tinzaparin was injected in the afferent blood line shortly after the start of the session. The doses had been defined prior to the start of the study, based on the presence or absence of visible clotting of membrane and circuit and/or prolonged bleeding after dialysis.
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Arm title
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IN5-OUT0-IN0 | |||||||||||||||||||||||||||||||||||
Arm description |
Administration of tinzaparin in this arm the first week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the second week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the third week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
tinzaparin
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Investigational medicinal product code |
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Other name |
Innohep, Leo Pharmaceutical Corp, Ballerup, Denmark
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Haemodialysis
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Dosage and administration details |
Tinzaparin with median and interquartile range of 4500 (3500–4500) IU was routinely used. Before the study, tinzaparin was injected in the afferent blood line shortly after the start of the session. The doses had been defined prior to the start of the study, based on the presence or absence of visible clotting of membrane and circuit and/or prolonged bleeding after dialysis.
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
IN0-OUT0-IN5
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0), the second week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the third week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) | ||
Reporting group title |
IN0-IN5-OUT0
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0), the second week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the third week: administration at the outlet blood line just prior the start of the blood pump (OUT0) | ||
Reporting group title |
OUT0-IN5-IN0
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the second week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the third week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) | ||
Reporting group title |
OUT0-IN0-IN5
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the second week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) the third week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) | ||
Reporting group title |
IN5-IN0-OUT0
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the second week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) the third week: administration at the outlet blood line just prior the start of the blood pump (OUT0) | ||
Reporting group title |
IN5-OUT0-IN0
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the second week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the third week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) | ||
Subject analysis set title |
IN0
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
analysis of the data of administration of tinzaparin at the inlet blood line just before the start of the blood pump
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Subject analysis set title |
IN5
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
analysis of the data of administration of tinzaparin at the inlet blood line 5 minutes after the detection of blood by the blood detector
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Subject analysis set title |
OUT0
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
analysis of the data of administration of tinzaparin at the outlet blood line just prior the start of the blood pump
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End point title |
anti-Xa activity at the end of the session | ||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
anti-Xa activity at the end of the heamodiafiltration session
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Statistical analysis title |
chi square test | ||||||||||||||||
Statistical analysis description |
continuous paired data were analyzed with repeated measures analysis of variance (Friedman) followed by Wilcoxon in case of significance. Chi square test was performed for categorical variables. Correlations were tested with Spearman correlation test.
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Comparison groups |
IN0 v IN5 v OUT0
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Number of subjects included in analysis |
39
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Analysis specification |
Post-hoc
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Analysis type |
other | ||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||
Method |
Chi-squared | ||||||||||||||||
Confidence interval |
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End point title |
anti-Xa activity during the session | ||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Anti-Xa activity measured pre, 30min, 120min and 180min of the heamodiafiltration session
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Statistical analysis title |
chi square test | ||||||||||||||||||||||||||||||||
Statistical analysis description |
Continuous paired data were analyzed with repeated measures analysis of variance (Friedman) followed by Wilcoxon in case of significance. Chi square test was performed for categorical variables. Correlations were tested with Spearman correlation test.
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Comparison groups |
IN5 v IN0 v OUT0
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Number of subjects included in analysis |
39
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Analysis specification |
Post-hoc
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Analysis type |
other | ||||||||||||||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||||||||||||||
Method |
Chi-squared | ||||||||||||||||||||||||||||||||
Confidence interval |
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End point title |
Endogenous Thrombin Potential (ETP) | ||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
ETP measured pre, 30min, 120min, 180min and 240 min of the heamodiafiltration session
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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 |
overall trial
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5.0
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Reporting groups
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Reporting group title |
IN0-OUT0-IN5
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0), the second week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the third week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
IN0-IN5-OUT0
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0), the second week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the third week: administration at the outlet blood line just prior the start of the blood pump (OUT0) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
OUT0-IN5-IN0
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the second week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the third week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
OUT0-IN0-IN5
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the second week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) the third week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
IN5-IN0-OUT0
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the second week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) the third week: administration at the outlet blood line just prior the start of the blood pump (OUT0) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
IN5-OUT0-IN0
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Reporting group description |
Administration of tinzaparin in this arm the first week: administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) the second week: administration at the outlet blood line just prior the start of the blood pump (OUT0) the third week: administration of tinzaparin at the inlet blood line just before the start of the blood pump (IN0) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: No non-serious adverse events were found for these results |
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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? 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 | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/26076014 |