Clinical Trial Results:
PEntoxifylline in Anaemia Resistant to erythropoietin (PEAR)
Summary
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EudraCT number |
2011-006168-30 |
Trial protocol |
GB |
Global end of trial date |
20 Sep 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Apr 2019
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First version publication date |
21 Apr 2019
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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 |
RLH_Pentoxifylline_Dec2011
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Barts Health NHS Trust
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Sponsor organisation address |
Whitechapel, London, United Kingdom, E1 1BB
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Public contact |
Dr Stanley FAN, Barts and The London NHS Trust, 44 2073777480, s.fan@qmul.ac.uk
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Scientific contact |
Dr Stanley FAN, Barts and The London NHS Trust, 44 2073777480, s.fan@qmul.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 |
20 Sep 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Sep 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Sep 2017
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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 |
To study the effects Pentoxifylline in ESA resistant ESRD patients on haemodialysis.
The primary study endpoints is the ESA requirement relative to the Hb level (is there a difference in a randomised placebo controlled cross-over study)?
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Protection of trial subjects |
But we had a safety committee comprised of other renal consultants who were not involved with the study
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
02 Apr 2012
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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: 84
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Worldwide total number of subjects |
84
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EEA total number of subjects |
84
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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) |
55
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From 65 to 84 years |
29
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||
Pre-assignment
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Screening details |
2 week screening run-in period. Subjects will attend their Dialysis Unit (run by BHT )for their standard hemodialysis on Day 1 (visit 1).Subjects will be entered in a run-in period for 2 weeks where biochemistry and haematology will be measure weekly (+/-3 days) to establish baseline. All blood tests will be taken prior to a dialysis session. | |||||||||||||||
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 | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Pentoxy | |||||||||||||||
Arm description |
Trental 400 | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Pentoxyphylline
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Investigational medicinal product code |
Pentoxyphylline
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Other name |
Trental 400
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
1 capsule per day (overencapsulated Trental 400)
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Arm title
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Placebo | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 84 patients consented to the study. However, this study included a run-in period (before randomisation) and during this time, some patients withdrew. Hence the baseline numbers total 69 and not the initial "full" 84 |
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Baseline characteristics reporting groups
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Reporting group title |
Pentoxy
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Reporting group description |
Trental 400 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pentoxy
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Reporting group description |
Trental 400 | ||
Reporting group title |
Placebo
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Reporting group description |
- |
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End point title |
ESA dose in iu / Hb in g/dl | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
6 months with last result carried forward
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Attachments |
Untitled (Filename: Outcome_ESA-Hb_1.pdf) |
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Statistical analysis title |
Primary ESA/Hb analysis | ||||||||||||
Statistical analysis description |
Primary end point was compared as difference in mean of ESA dose relative to haemoglobin between first two readings during run in period and last two readings during follow up period in experimental and placebo groups using unpaired student t-test. P values of < 0.05 will be considered statistically significant
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Comparison groups |
Pentoxy v Placebo
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Number of subjects included in analysis |
66
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
6 months
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
Own specified list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
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Reporting group title |
IMP arm
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Reporting group description |
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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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28 Feb 2013 |
We applying for the substantial amendment because in the original application the Active IMP, pentoxifylline 400mg prolonged release tablets (Trental), was to be sourced from Germany. Since then, our IMP supplier has informed us that the German product has become unavailable for export, so the IMP is now to be sourced from Portugal. Trental as marketed in Portugal has the Marketing Authorisation (registration) number 4600284 (packs of 60) |
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20 Mar 2013 |
After careful consideration of the recent literature and the funding situation, we should like to remove the “experimental end-points” in the protocol. However, we shall still be consenting patients to have bloods stored for future research. For this reason, we will not change the number, volume or the frequency of the blood tests. As per original protocol, blood will be stored in a HTA approved tissue bank. If we decide to analysis of these stored blood samples at a future date, we shall submit a new study protocol and seek ethical approval prior to any analysis.
We believe that there would be potential ethical issues if we were performed tests on patients that are no longer relevant given the current literature. We believe the scientific validity of the study will not be compromised as we are seeking consent for blood to be stored. These can be analysed for experimental end-points at a future date (subject to a different study protocol/ethic submission).
Because the frequency and the amount of blood / intervention is unchanged, we have not felt it necessary to amend the Patient Information Sheet (remaining version 4-1 27th Nov 2012). |
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01 Nov 2013 |
1. Changes to the inclusion crieteria:
a. Removal of CRP > 5 as one of the inclusion crieteria
b. Erythropoietin stimulating agent (ESA) dose has been changed to erythropoietin dose greater than or equal to 6000 iu equivalent of EPO (erythropoietin) per week or if ESA resistance index is greater than or equal to 6.5 iu /kg/wk/g Hb for equivalent EPO dose to maintain stable haemoglobin levels. This dose is similar to median ESA requirement for haemodialysis patients with arterio venous fistula as dialysis access in our unit.
2. Changes to FDG - PET / CT scan protocol :
Following the review of initial 5 scans research team has changed the FDG-PET / CT protocol. The new protocol will provide sufficient data for secondary end point analysis.
The duration of dynamic imaging for the PET scan has been changed from 0 to 50 minutes to 0 to 60 minutes. The initial protocol of whole body imaging at 60 min and 160 min has now been changed to single whole body imaging at 90 min. The number of venous blood samples during the dynamic imaging has also been reduced to total 11 samples ( total blood volume 33 mls per scan) from total 21 blood samples (total blood volume 63mls per scan).
This change in imaging protocol had to be implemented before formal approval because there is better patient experience during the scan visit and reduced radiation exposure to patients with no compromise to the quality of data obtained.
3. Patient information sheet has also been modified based in view of change in FDG-PET/CT protocol. Total imaging time for FDG-PET/CT scan has been reduced to 2 hrs compared to 4 hrs previously. |
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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 |