Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Branch Retinal Vein Occlusion (BRVO)

Macular Edema Clinical Trial

— COMRADE-B  

Official title:

A 6-month Multicenter, Randomized, Double-masked Phase IIIb-study Comparing the Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Visual Impairment Due to Macular Edema Following Branch Retinal Vein Occlusion (BRVO)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01396057
• Other study ID #: CRFB002EDE17
• Secondary ID: 2011-001019-30
• Status: Completed
• Phase: Phase 3
• First received: July 14, 2011
• Last updated: August 4, 2014
• Start date: July 2011
• Est. completion date: June 2013

Study information

• Verified date: August 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

This clinical trial is designed to compare ranibizumab in comparison with Dexamethasone implant after 6 months of treatment. In the study arm Ranibizumab will be given monthly in a pro re nata scheme whereas the comparator Dexamethasone implant is given once at Month 0 with sham injections PRN afterwards.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 244
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients diagnosed with visual impairment due to macular edema following BRVO

• Diagnosis of BRVO at maximum 6 months prior to Screening

• BCVA using ETDRS charts of 20/40 to 20/400 in the study eye

Exclusion Criteria:

• Media clarity, pupillary dilation and patient cooperation not sufficient for adequate fundus photographs

• Central retinal thickness (CRT) < 250 µm in the study eye

• Prior episode of RVO in the study eye

• Active formation of new vessels in the study eye

• Anti-VEGF-treatment in the study or the fellow eye 3 months prior to Baseline

• IOP = 30mmHg or uncontrolled glaucoma; patients may be re-screened after 1 month if they have undergone glaucoma treatment

• Improvement of > 10 letters on BCVA between Screening and Baseline

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Branch Retinal Vein Occlusion
• Macular Edema
• Retinal Vein Occlusion
• Visual Impairment

Intervention

Drug:
• Ranibizumab
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally. Ranibizumab was formulated as a sterile solution aseptically filled in a sterile glass vial. It was suitable for single use only and the content of the vial was not allowed to be split

Other:
• Dexamethasone Implant
Comparator Ozurdex® (dexamethasone) was formulated as a rod shaped implant to be inserted into the eye by an applicator. The implant as well as the respective applicator were suitable for single use only.
• Sham injection
Sham injection: Empty sterile syringes were provided so that masking could be maintained. Either empty syringes in the case of sham injections or pre-filled syringes in the case of ranibizumab injections were visible to the patient in the room of study drug administration

Locations

Country	Name	City	State
Czech Republic	Novartis Investigative Site	Praha 10
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Bad Rothenfelde
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Bremen
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Düsseldorf
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg i. Br
Germany	Novartis Investigative Site	Glauchau
Germany	Novartis Investigative Site	Göttingen
Germany	Novartis Investigative Site	Hagen
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Ingolstadt
Germany	Novartis Investigative Site	Karlsruhe
Germany	Novartis Investigative Site	Karlsruhe
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Ludwigshafen
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Minden
Germany	Novartis Investigative Site	Muelheim
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Munich
Germany	Novartis Investigative Site	Recklinghausen
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Sulzbach
Germany	Novartis Investigative Site	Tübingen
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Wolfsburg
Germany	Novartis Investigative Site	Würzburg
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Szeged
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Bytom
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bradford
United Kingdom	Novartis Investigative Site	Cheshire
United Kingdom	Novartis Investigative Site	Colchester
United Kingdom	Novartis Investigative Site	Derby
United Kingdom	Novartis Investigative Site	Gloucester
United Kingdom	Novartis Investigative Site	Guildford, Surrey
United Kingdom	Novartis Investigative Site	Kent
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Middlesborough
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Portsmouth
United Kingdom	Novartis Investigative Site	Rugby
United Kingdom	Novartis Investigative Site	Westcliff-on-Sea
United Kingdom	Novartis Investigative Site	York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Czech Republic,  Germany,  Hungary,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Average Best Corrected Visual Acuity (BCVA) Change From Month 1 Through Month 6 to Baseline	the average of the changes in BCVA (letters) from baseline to any post-baseline visit, i.e. the mean of six differences to baseline for the six post-baseline visits at month 1 to 6	Baseline, month 6	No
Secondary	Mean BCVA Change From Baseline to Endpoints Month 1 to Month 6	The analysis was performed by an analysis of covariance (ANCOVA) model with average change in BCVA (letters) from Visit 1 through Visit 6 as dependent variable, and with the factors center, treatment and covariate baseline BCVA as predictors	Baseline, month 6	No
Secondary	Percentage of Patients Gaining / Losing = 15 / 10 / 5 Letters After 6 Month Treatment	BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increased score indicates improvement in acuity. This outcome assessed the percentage of participants who gained 15, 10 or 5 more letters of visual acuity at month 6 as compared with baseline	Baseline, 6 month	No
Secondary	Time to Achieve a Significant Improvement = 15 Letters	The time was analyzed by the Kaplan-Maier-Method, adjusting the calculation for dropouts	Baseline, month 6	No
Secondary	Change Over Time in BCVA	The analysis was performed by an analysis of covariance (ANCOVA) model with average change in BCVA (letters) from Visit 1 through Visit 6 as dependent variable, and with the factors center, treatment and covariate baseline BCVA as predictors	baseline, month 6	No
Secondary	Change Over Time of the Central Retinal Thickness (CRT)	Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation	Baseline, month 6	No
Secondary	Changes in the Quality of Life According to the National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) Questionnaires	The VFQ-25 composite and subscale scores range from 0 to 100, a higher score indicating better functioning. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated improvement in quality of life due to vision function.	Baseline, month 6	No
Secondary	Changes in the Quality of Life According to the Short Form (36) Health Survey (SF-36)Questionnaires	SF-36 summary measures are norm-based scores with mean = 50 and SD = 10. Higher scores indicate better health	Baseline, month 6	No
Secondary	Changes in the Quality of Life According to Euro Quality of Life (EQ-5D) Questionnaires	The EQ-5D visual analog scale ranges from 0 to 100, 0 representing the worst and 100 the best imaginable health state.	Baseline, month 6	No
Secondary	Rate of the Internal Ocular Pressure (IOP)	The proportion of patients with = 10% increase in IOP compared to baseline at any post-baseline visit.	Baseline, month 6	Yes