Clinical Trial Results:
Triamcinolone acetonide to prevent PVR in eyes undergoing vitreoretinal surgery for open globe trauma
Summary
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EudraCT number |
2007-005138-35 |
Trial protocol |
GB |
Global end of trial date |
30 May 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Jun 2019
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First version publication date |
28 Jun 2019
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Other versions |
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Summary report(s) |
End of Study Summary Report |
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 |
CHAD1024
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Moorfields Eye Hospital NHS Foundation Trust
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Sponsor organisation address |
162 City Road, London, United Kingdom, EC1V 2PD
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Public contact |
Tania West (R&D office), Moorfields Eye Hospital, 020 72, moorfields.resadmin@nhs.net
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Scientific contact |
Tania West (R&D office), Moorfields Eye Hospital, 020 72533411, moorfields.resadmin@nhs.net
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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 |
01 Oct 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 May 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
30 May 2014
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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 |
This is a pilot RCT to investigate the the effect of the use of peroperative intravitreal triamcinilone acetate in the development of proliferative vitreoretinopathy following open globe trauma.
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Protection of trial subjects |
safety and data reviewed by Moorfields internal DMC
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Background therapy |
Surgical repair of ocular trauma | ||
Evidence for comparator |
Eyes sustaining penetrating or open globe trauma (OGT) are a group at high risk of severe visual impairment. Retinal detachment is common in these eyes and multiple surgical interventions are often necessary 12, 13. PVR is the commonest cause of recurrent retinal detachment and visual loss in eyes with open globe trauma. It is estimated to occur in 10-45% of all OGT. 8-14 8. Cardillo JA, Stout JT, LaBree L, et al. Post-traumatic proliferative vitreoretinopathy. The epidemiologic profile, onset, risk factors, and visual outcome. Ophthalmology 1997;104(7):1166-73. 9. Spiegel D, Nasemann J, Nawrocki J, Gabel VP. Severe ocular trauma managed with primary pars plana vitrectomy and silicone oil. Retina 1997;17(4):275-85. 10. Framme C, Roider J. [Epidemiology of open globe injuries]. Klin Monbl Augenheilkd 1999;215(5):287-93. 11. Mittra RA, Mieler WF. Controversies in the management of open-globe injuries involving the posterior segment. Surv Ophthalmol 1999;44(3):215-25. 12. Stryjewski TP, Andreoli CM, Eliott D. Retinal detachment after open globe injury. Ophthalmology 2014;121(1):327-33. 13. Andreoli MT, Andreoli CM. Surgical rehabilitation of the open globe injury patient. Am J Ophthalmol 2012;153(5):856-60. 14. Desai P, MacEwen CJ, Baines P, Minassian DC. Incidence of cases of ocular trauma admitted to hospital and incidence of blinding outcome. Br J Ophthalmol 1996;80(7):592-6. | ||
Actual start date of recruitment |
01 Sep 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 |
United Kingdom: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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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) |
40
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
40 patients with open globe ocular trauma recruited between September 20111 and November 2013 | ||||||
Pre-assignment
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Screening details |
45 patients screened for inclusion - 4 failed to meet inclusion criteria, one declined participation | ||||||
Period 1
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Period 1 title |
recruitment (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | ||||||
Roles blinded |
Investigator [1] | ||||||
Blinding implementation details |
Patient and assessor blinded
Investigator - surgeon - providing treatment , (no placebo) not blinded
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Arms
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Arm title
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Treatment | ||||||
Arm description |
TREATMENT GROUP a. Pre-operative Treatment Guttae Prednisolone forte 2 hourly for up to one week. b. Per-operative Treatment 4mg of intravitreal triamcinolone acetonide will be injected into the vitreous cavity following injection of silicone oil at the end of procedure 40mg of triamcinolone acetonide will be given as a posterior subtenons injection prior to suturing the conjunctiva. c. Post-operative Treatment Hourly g. Predforte for 1 week followed by a tapering regimen for 3-26 weeks thereafter depending on the degree of post-operative inflammation and cystoid macular oedema. 50mg flurbiprofen orally bid for 1 week | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
triamcinolone acetonide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intraocular use
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Dosage and administration details |
Intraoperative treatment: (a) 4 mg/0.1 ml of intravitreal triamcinolone
acetonide (Bristol Myers Squibb, UK) was injected into
the vitreous cavity following closure of the scleral ports at the
end of procedure, (b) 40 mg/1 mL of triamcinolone acetonide
(Bristol Myers Squibb, UK) was administered as a posterior subtenons
injection prior to suturing the conjunctiva and (c) standard
subconjunctival antibiotic injection of cefuroxime 125 mg
or gentamicin was administered
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Investigational medicinal product name |
prednisolone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Eye drops
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Routes of administration |
Conjunctival use
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Dosage and administration details |
(a) Guttae prednisolone forte hourly for 1 week followed by a
tapering regimen for 3–26 weeks thereafter depending on the
degree of postoperative inflammation and cystoid macular
oedema,
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Investigational medicinal product name |
flurbiprofen
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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 |
50 mg flurbiprofen orally twice daily for 1 week
and
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Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: Investigator administers treatment and there is no placebo |
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Notes [2] - 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: Investigator administers treatment and sees trial medication - no placebo |
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
TREATMENT GROUP a. Pre-operative Treatment Guttae Prednisolone forte 2 hourly for up to one week. b. Per-operative Treatment 4mg of intravitreal triamcinolone acetonide will be injected into the vitreous cavity following injection of silicone oil at the end of procedure 40mg of triamcinolone acetonide will be given as a posterior subtenons injection prior to suturing the conjunctiva. c. Post-operative Treatment Hourly g. Predforte for 1 week followed by a tapering regimen for 3-26 weeks thereafter depending on the degree of post-operative inflammation and cystoid macular oedema. 50mg flurbiprofen orally bid for 1 week | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
treatment group
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
treatment group analysed v controls
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Subject analysis set title |
control group
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
analyse dv treatment group
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End points reporting groups
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Reporting group title |
Treatment
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Reporting group description |
TREATMENT GROUP a. Pre-operative Treatment Guttae Prednisolone forte 2 hourly for up to one week. b. Per-operative Treatment 4mg of intravitreal triamcinolone acetonide will be injected into the vitreous cavity following injection of silicone oil at the end of procedure 40mg of triamcinolone acetonide will be given as a posterior subtenons injection prior to suturing the conjunctiva. c. Post-operative Treatment Hourly g. Predforte for 1 week followed by a tapering regimen for 3-26 weeks thereafter depending on the degree of post-operative inflammation and cystoid macular oedema. 50mg flurbiprofen orally bid for 1 week | ||
Subject analysis set title |
treatment group
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
treatment group analysed v controls
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Subject analysis set title |
control group
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
analyse dv treatment group
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End point title |
The primary outcome measure was anatomic reapposition of | ||||||||||||
End point description |
primary outcome measure
The primary outcome measure was anatomic reapposition of
the remaining retina to the retinal pigment epithelium in the
absence of an internal tamponade agent at 6 months postprimary
vitrectomy surgery
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End point type |
Primary
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End point timeframe |
6 months
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Statistical analysis title |
Analysis | ||||||||||||
Statistical analysis description |
The time taken to recruit patients is reported together with the
number of patients who failed to provide outcome data.
Baseline characteristics of the two groups were compared to
assess the adequacy of randomisation. The OR of patients in
whom anatomical retinal attachment remained at 6 months postprimary
vitrectomy between the two treatment groups was
reported with 95% CIs
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Comparison groups |
treatment group v control group
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
< 0.5 [2] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
1.1
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.316 | ||||||||||||
upper limit |
3.904 | ||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.1
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Notes [1] - A total of 40 patients was considered a feasible number over the study period and expected to provide sufficient data to estimate the SD to power a definitive study [2] - Not applicable |
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Adverse events information
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Timeframe for reporting adverse events |
Period of study - 6 month follow up
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Assessment type |
Systematic | ||||||||||||||||||||||||
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 |
treatment
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Reporting group description |
The number of adverse events (AEs) was comparable across both groups with 18 out of 20 adjunct patients suffering at least one AE compared with 16 of 20 control patients. There were no cases of postoperative endophthalmitis in either group. A slightly higher number of patients in the adjunct group (n=7, 35%) suffered at least one episode of elevated intraocular pressure (IOP) (>25 mm Hg) compared with five (25%) patients in the control group. . A higher median IOP was noted in the adjunct group at day 10, but this subsequently becomes comparable between the two groups. There were more cases of postoperative uveitis in the control group (n=5) in comparison to the adjunct group (n=2). An equal number of patients (n=5) suffered at least one episode of hypotony (IOP <6 mm Hg) during the trial. | ||||||||||||||||||||||||
Reporting group title |
control
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Reporting group description |
The number of adverse events (AEs) was comparable across both groups with 18 out of 20 adjunct patients suffering at least one AE compared with 16 of 20 control patients. There were no cases of postoperative endophthalmitis in either group. A slightly higher number of patients in the adjunct group (n=7, 35%) suffered at least one episode of elevated intraocular pressure (IOP) (>25 mm Hg) compared with five (25%) patients in the control group. The median IOP readings at each time point is displayed in the box plot of figure 3. A higher median IOP was noted in the adjunct group at day 10, but this subsequently becomes comparable between the two groups. There were more cases of postoperative uveitis in the control group (n=5) in comparison to the adjunct group (n=2). An equal number of patients (n=5) suffered at least one episode of hypotony (IOP <6 mm Hg) during the trial. | ||||||||||||||||||||||||
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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/26546051 |