Clinical Trial Results:
Management of recurrent pterygium to prevent visual impairment(REPEAT)
Summary
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EudraCT number |
2015-003217-20 |
Trial protocol |
GB |
Global end of trial date |
11 Apr 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Apr 2019
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First version publication date |
25 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 |
15073
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02530801 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
University of Nottingham
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Sponsor organisation address |
Jubilee Campus, Triumph Road, Nottingham, United Kingdom, NG8 1DH
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Public contact |
Harminder Dua, University of Nottingham, 0115 9709796, harminder.dua@nottingham.ac.uk
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Scientific contact |
Harminder Dua, University of Nottingham, 0115 8467906, sponsor@nottingham.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 |
04 Apr 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Apr 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Apr 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 |
To assess the efficacy of combined 5FU and Avastin injections in the treatment of recurrent pterygium.
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Protection of trial subjects |
Pregnant women, women aiming for conception, and nursing mothers were excluded from the study. Patients under 18 years of age were also excluded. Dose adjustment was not expected to be needed for patients with renal or hepatic impairment. There is no evidence in the literature that it affects spermatogenesis in men who are aiming to father a child. Therefore they were not excluded from the study but were informed that there is no evidence in the literature regarding whether Avastin® can affect sperm.
Participants were asked to contact the study site immediately in the event of any serious adverse event. History would be taken and recorded and meticulous eye examination done for the patient. All adverse events were recorded, appropriately treated and closely monitored until resolution, stabilisation, or until it has been shown that the study medication or treatment is not the cause. The Chief Investigator (delegated responsibility by the Sponsor) would be informed immediately (within 24 hours) of any serious adverse events and would determine seriousness and causality in conjunction with any treating medical practitioners.
All serious adverse events were to be recorded and reported to the MHRA and REC as part of the annual Development Safety Update Reports. SUSARs were to be reported within the statutory timeframes to the MHRA and REC as stated below.
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Background therapy |
Antibiotic eye drops (chloramphenicol) | ||
Evidence for comparator |
No comparator was used for this trial. | ||
Actual start date of recruitment |
01 Dec 2015
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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: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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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) |
16
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were recruited from specialist cornea and ocular surface clinics of Professor HS Dua at Nottingham University Hospitals NHS Trust between 10.01.2017 and 09.11.2017. The trial setting is a secondary care hospital in the UK. | ||||||
Pre-assignment
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Screening details |
Patient meets all eligibility criteria as per protocol including age over the age of 18, able to give informed consent, presenting with either early or recurrent pterygium, able to tolerate injection, not pregnant or breastfeeding or planning on becoming pregnant, do not have concurrent eye conditions that would make them unsuitable. | ||||||
Period 1
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Period 1 title |
Pre-injection
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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Treatment Group | ||||||
Arm description |
Patients receiving Avastin and 5 flurouracil. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
5 Fluorouracil
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subconjunctival use
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Dosage and administration details |
0.15 ml of 5FU (3.75mg) administered into the body of the pterygium. Up to 5 injections at 5 visits could be given.
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Investigational medicinal product name |
Bevacizumab
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Investigational medicinal product code |
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Other name |
Avastin
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subconjunctival use
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Dosage and administration details |
0.15 ml of Avastin® (3.75mg) administered in the body of the pterygium lesion. Up to 5 injections at 5 visits could be given.
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Period 2
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Period 2 title |
Post-injection series
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Is this the baseline period? |
No | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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Treatment Group | ||||||
Arm description |
Patients receiving Avastin and 5 flurouracil. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
5 Fluorouracil
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subconjunctival use
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Dosage and administration details |
0.15 ml of 5FU (3.75mg) administered into the body of the pterygium. Up to 5 injections at 5 visits could be given.
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Investigational medicinal product name |
Bevacizumab
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Investigational medicinal product code |
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Other name |
Avastin
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subconjunctival use
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Dosage and administration details |
0.15 ml of Avastin® (3.75mg) administered in the body of the pterygium lesion. Up to 5 injections at 5 visits could be given.
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Baseline characteristics reporting groups
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Reporting group title |
Pre-injection
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Treatment Group
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Reporting group description |
Patients receiving Avastin and 5 flurouracil. | ||
Reporting group title |
Treatment Group
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Reporting group description |
Patients receiving Avastin and 5 flurouracil. |
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End point title |
Arrest of progression and/or regression of thickness of the conjunctiva at the site of the lesion. | ||||||||||||
End point description |
The response to treatment was judged clinically by biomicroscopy examination (when no further advance of the lesion was noted over three follow-up visits, 1-2 weeks apart) and quantitatively by comparison with pre-treatment slit lamp photographs (arrest of progression and/or regression of vascularity and thickness of the conjunctiva at the site of the lesion). The degree of vascularity and thickness of the conjunctiva was assessed using a semi- automatic method by comparison of the pre and post treatment digital eye photographs by two independent blind reviewers.
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End point type |
Primary
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End point timeframe |
After a maximum of 5 injections of 5FU and Avastin over the course of six months
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Notes [1] - 20 subjects were analysed pre and post their series of injections. [2] - 20 subjects were analysed pre and post their series of injections. |
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Statistical analysis title |
Reduction in thickness pre and post injection | ||||||||||||
Statistical analysis description |
As this is a single arm trial the comparison groups are the 20 participants pre and post injection.
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Comparison groups |
Treatment Group v Treatment Group
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | ||||||||||||
P-value |
= 0.0078 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
35.8
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
11.7 | ||||||||||||
upper limit |
59.9 | ||||||||||||
Notes [3] - Comparison of pterygium thickness pre and post injection series. |
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End point title |
Disappearance of redness | ||||||||||||
End point description |
Mean reduction in clinical grade post injection.
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End point type |
Secondary
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End point timeframe |
After a maximum of five injections over a six month period.
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Notes [4] - 20 subjects were analysed pre and post their series of injections. [5] - 20 subjects were analysed pre and post their series of injections. |
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Statistical analysis title |
Reduction in clinical grade pre and post injection | ||||||||||||
Comparison groups |
Treatment Group v Treatment Group
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
other [6] | ||||||||||||
P-value |
= 0.0004 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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sides |
2-sided
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lower limit |
0.367 | ||||||||||||
upper limit |
1.008 | ||||||||||||
Notes [6] - Reduction in clinical grade pre and post injection |
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Adverse events information
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Timeframe for reporting adverse events |
Up to 2 weeks post-injection.
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Adverse event reporting additional description |
Participants will be asked to contact the study site immediately in the event of any serious adverse event. All adverse events will be recorded and closely monitored until resolution, stabilisation, or until it has been shown that the study medication or treatment is not the cause.
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Assessment type |
Systematic | ||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
All participants who received Avastin and 5 Fluorouracil. | ||||||||||||||
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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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22 Jun 2016 |
Primary pterygium was added to the inclusion criteria and the sample size was increased to 40. An additional co-investigator was added. |
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12 Jan 2017 |
A tissue collection sub-study was added to obtain consent from patients who received injections to use the pterygium tissue after being surgically excised, as surgical excision is the standard care in pterygium patients, and also from patients who have had injections as part of their normal standard of care outside the study as they may also have their residual pterygium excised. The tissue was to be examined to ascertain what effect the injections had on the pterygium. This tissue is normally sent to the laboratory for routine examination under the microscope. The tissue will be disposed of at the end of the study in accordance with the Human Tissue Act. |
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26 Mar 2018 |
Consent to be sought from participants that any remaining pterygium tissue samples may be stored and used in possible future research. |
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09 Apr 2018 |
Inclusion of the retrospective data of the patients who have already received the treatment in the protocol as part of their NHS standard care. Thirteen patients have already provided their
consent, using the information sheet and consent form which talk about their prospective treatment, but it was clearly explained to them that they were consenting to the use of their
retrospective data, where they have already received the trial treatment as part of their standard care. |
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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. | |||
Although the recruitment target had been amended to 40, the decision was made to stop recruitment at 20 participants as sufficient data was collected to achieve the protocol objectives. |