Clinical Trial Results:
Intravitreal Ranibizumab in pigment epithelial tears secondary to age- related macular degeneration - RIP Study
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Summary
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EudraCT number |
2011-005807-33 |
Trial protocol |
DE |
Global end of trial date |
27 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Sep 2021
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First version publication date |
19 Sep 2021
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Other versions |
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Summary report(s) |
Medical journal article |
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 |
Version_V3_0
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01914159 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Bonn
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Sponsor organisation address |
Sigmund-Freud-Str. 25, Bonn, Germany, 53105
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Public contact |
Dr. Christoph Coch, CSSC - Studienzentrale, ccoch@uni-bonn.de
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Scientific contact |
Dr. Christoph Coch, CSSC - Studienzentrale, ccoch@uni-bonn.de
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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 |
09 Feb 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
27 Jan 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Jan 2016
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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 purpose of the study is to investigate the effect of ranibizumab in retinal pigment epithelium tears in the presence of pigment epithelial detachments in AMD.
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Protection of trial subjects |
Not applicable
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Background therapy |
Not applicable | ||
Evidence for comparator |
The efficacy of intravitreal anti-VEGF therapy in neovascular AMD has been demonstrated in various prospective large-scale clinical trials, whereby the presence of an RPE tear constituted an exclusion criterion in all of these trials. Thus, the efficacy of anti-VEGF therapy in this AMD subtype is unclear. To the best of our knowledge, the RIP study provides the first prospective efficacy data for anti-VEGF therapy in RPE tears secondary to AMD, demonstrating a stabilization of visual acuity under monthly ranibizumab therapy over 12 months. | ||
Actual start date of recruitment |
15 Nov 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 |
Germany: 24
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Worldwide total number of subjects |
24
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EEA total number of subjects |
24
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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) |
0
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From 65 to 84 years |
23
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85 years and over |
1
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Recruitment
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Recruitment details |
Study patients were recruited over a period of 26 months (02/2013 bis 04/2015) at the Departments of Ophthalmology of University of Bonn, University of Münster, and Ludwig Maximilian University Munich. | ||||||||||
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Pre-assignment
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Screening details |
Only patients with neovascular activity of the AMD were included into the study. A total of 29 patients were screened for this study during the recruitment period, and 5 of these did not meet the eligibility criteria. Thus, 24 eyes of 24 patients were included in this study. | ||||||||||
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Period 1
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Period 1 title |
Baseline (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 |
All patients received monthly intravitreal injections of ranibizumab (0.5mg) into the study eye over the study period of 12 months. Prior to each injection, patients were examined by standardized BCVA testing according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol, dilated fundus examination, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence imaging.
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Arms
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Arm title
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Single-arm-trial Baseline | ||||||||||
Arm description |
All patients received monthly intravitreal injections of ranibizumab (0.5mg) into the study eye over the study period of 12 months. Prior to each injection, patients were examined by standardized BCVA testing according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol, dilated fundus examination, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence imaging. At baseline, additionally color fundus photography and fluorescein and indocyanine green angiography was performed to establish and document the diagnosis. Vision-related quality of life was assessed at baseline and final visit using the National Eye Institute 25 Item Visual Function Questionnaire (NEI VFQ-25). | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Lucentis
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Investigational medicinal product code |
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Other name |
Ranibizumab
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
Concentration: 10 mg/ml
Single dose: 0.5 mg
Administration: Monthly injection into the vitreous humour (intravitreal)
Duration of treatment: 12 months
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
As there is only one treatment arm, characteristics apply to all subjects. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Single-arm-trial Baseline
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Reporting group description |
All patients received monthly intravitreal injections of ranibizumab (0.5mg) into the study eye over the study period of 12 months. Prior to each injection, patients were examined by standardized BCVA testing according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol, dilated fundus examination, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence imaging. At baseline, additionally color fundus photography and fluorescein and indocyanine green angiography was performed to establish and document the diagnosis. Vision-related quality of life was assessed at baseline and final visit using the National Eye Institute 25 Item Visual Function Questionnaire (NEI VFQ-25). | ||
Subject analysis set title |
Final visit
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The primary endpoint is BCVA after treatment conclusion (one month after final injection) compared to
baseline.
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End point title |
BCVA change between baseline and V13 | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
The primary endpoint is BCVA after treatment conclusion (one month after final injection) compared to baseline.
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Statistical analysis title |
BCVA change between baseline and V13 | |||||||||
Statistical analysis description |
Study results were analyzed according to the intention-to–treat principle, and no last-observation-carried-forward approach was applied to drop-outs.
Mean baseline BCVA for all 24 eyes was 50.3 ETDRS letters (±18.7). Mean BCVA at final study visit was 52.9 letters (±19.7). There was no significant difference between these values (P = 0.39).
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Comparison groups |
Single-arm-trial Baseline v Final visit
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Number of subjects included in analysis |
45
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
P-value |
= 0.39 [2] | |||||||||
Method |
t-test, 2-sided | |||||||||
Confidence interval |
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| Notes [1] - Statistical significance was assessed using paired Student’s t test, and correlation was analyzed by Pearson’s correlation coefficient. All results are expressed as means ± standard deviation. [2] - Mean baseline BCVA for all 24 eyes was 50.3 ETDRS letters (± 18.7; Snellen equivalent 20/100; 0.69 logMAR ± 0.37). Mean BCVA at final study visit was 52.9 letters (± 19.7; Snellen equivalent 20/80; 0.64 logMAR ± 0.39). |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events reporting took place from start of recruitment in 02/2013 until final visit of final patient in 01/2016.
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Adverse event reporting additional description |
To assess safety data using the four eyes principle, in addition to the initial assessment of a serious adverse event by the investigator, a second assessment regarding severity, causality, and expectedness as well as a benefit-risk assessment will be undertaken by the second assessor.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
ICD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
Single-arm-trial
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Reporting group description |
All patients received monthly intravitreal injections of ranibizumab (0.5mg) into the study eye over the study period of 12 months. Prior to each injection, patients were examined by standardized BCVA testing according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol, dilated fundus examination, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence imaging. At baseline, additionally color fundus photography and fluorescein and indocyanine green angiography was performed to establish and document the diagnosis. Vision-related quality of life was assessed at baseline and final visit using the National Eye Institute 25 Item Visual Function Questionnaire (NEI VFQ-25). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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/30198967 |
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