Visual ImpairmentPhase 3COMRADE-BNCT01396057

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

A Phase 3 study testing Ranibizumab and Dexamethasone Implant in people with Visual Impairment and Macular Edema, run by Novartis Pharmaceuticals at 66 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Visual Impairment, Macular Edema, Branch Retinal Vein Occlusion
What is being tested?: Ranibizumab and Dexamethasone Implant
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 244 participants
Where: 66 sitesin 5 countries
Study dates: Jul 2011to Jun 2013
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

66 sites in 5 countries.

Country

City, postcode or hospital

66 sites in 5 countries

Germany42 sites

Novartis Investigative Site
Augsburg, 85155
Novartis Investigative Site
Bad Rothenfelde, 49215
Novartis Investigative Site
Berlin, 10713
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Bochum, 44791
Novartis Investigative Site
Bonn, 53127
Novartis Investigative Site
Bremen, 28209
Novartis Investigative Site
Chemnitz, 09116
Novartis Investigative Site
Cologne, 50935
Novartis Investigative Site
Darmstadt, 64298
Novartis Investigative Site
Dresden, 01257
Novartis Investigative Site
Düsseldorf, 40212
Novartis Investigative Site
Düsseldorf, 40225
Novartis Investigative Site
Frankfurt, 60318
Novartis Investigative Site
Freiburg I. Br, 79106
Novartis Investigative Site
Glauchau, 08371
Novartis Investigative Site
Göttingen, 37075
Novartis Investigative Site
Hagen, 58097
Novartis Investigative Site
Halle, 06114
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Hamburg, 22417
Novartis Investigative Site
Homburg, 66421
Novartis Investigative Site
Ingolstadt, 85049
Novartis Investigative Site
Karlsruhe, 76133
Novartis Investigative Site
Karlsruhe, 76199
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
Leipzig, Germany, 04103
Novartis Investigative Site
Ludwigshafen, 67063
Novartis Investigative Site
Marburg, 35039
Novartis Investigative Site
Minden, 32427
Novartis Investigative Site
Mülheim, 45468
Novartis Investigative Site
München, 81675
Novartis Investigative Site
Munich, 80336
Novartis Investigative Site
Münster, 48145
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Recklinghausen, 45657
Novartis Investigative Site
Regensburg, Germany, 93042
Novartis Investigative Site
Sulzbach, 66280
Novartis Investigative Site
Tübingen, 72076
Novartis Investigative Site
Ulm, 89075
Novartis Investigative Site
Wolfsburg, 38442
Novartis Investigative Site
Würzburg, 97080

Other trials in Germany

United Kingdom18 sites

Novartis Investigative Site
Birmingham, B152WB
Novartis Investigative Site
Birmingham, B18 7QU
Novartis Investigative Site
Bradford, BD9 6RJ
Novartis Investigative Site
Cheshire, CW14QJ
Novartis Investigative Site
Colchester, CO3 3NB
Novartis Investigative Site
Derby, DE22 3NE
Novartis Investigative Site
Gloucester, GL1 3NN
Novartis Investigative Site
Guildford, Surrey, GU2 5XX
Novartis Investigative Site
Kent, CT1 3NG
Novartis Investigative Site
Leeds, LS9 7TF
Novartis Investigative Site
London, SE1 7EH
Novartis Investigative Site
Manchester, M13 9WH
Novartis Investigative Site
Middlesbrough, TS4 3BW
Novartis Investigative Site
Nottingham, NG7 2UH
Novartis Investigative Site
Portsmouth, PO6 3LY
Novartis Investigative Site
Rugby, CV22 5PX
Novartis Investigative Site
Westcliff-on-Sea, SS0 0RY
Novartis Investigative Site
York, YO31 8HE

Other trials in United Kingdom

Hungary3 sites

Novartis Investigative Site
Budapest, 1083
Novartis Investigative Site
Debrecen, 4004
Novartis Investigative Site
Szeged, H-6720

Other trials in Hungary

Poland2 sites

Novartis Investigative Site
Bydgoszcz
Novartis Investigative Site
Bytom, 41-902

Other trials in Poland

Czechia1 site

Novartis Investigative Site
Prague, 100 34

Other trials in Czechia

About this study

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)

Conditions: Visual Impairment, Macular Edema, Branch Retinal Vein Occlusion
Being tested: Ranibizumab, Dexamethasone Implant, Sham injection
Keywords: Visual impairment, macular edema, branch retinal vein occlusion, Dexamethasone implant, Ranibizumab
Medical subject headings: Vision Disorders, Macular Edema, Retinal Vein Occlusion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RanibizumabDrug
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
Dexamethasone ImplantOther
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 injectionOther
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

Study groups in NCT01396057
Study group	Role	What they receive
Ranibizumab	Experimental	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally Receives: Drug: Ranibizumab
Dexamethasone	Sham comparator	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months Receives: Other: Dexamethasone Implant; Other: Sham injection

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Baseline, month 6

Secondary outcomes (9)

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
Measured: Baseline, month 6
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
Measured: Baseline, 6 month
Time to Achieve a Significant Improvement ≥ 15 Letters
The time was analyzed by the Kaplan-Maier-Method, adjusting the calculation for dropouts
Measured: Baseline, month 6
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
Measured: baseline, month 6
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
Measured: Baseline, month 6
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.
Measured: Baseline, month 6
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
Measured: Baseline, month 6
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.
Measured: Baseline, month 6
Rate of the Internal Ocular Pressure (IOP)
The proportion of patients with ≥ 10% increase in IOP compared to baseline at any post-baseline visit.
Measured: Baseline, month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2011Jun 2013

First posted18 Jul 2011 (estimated)
Study startJul 2011
Primary completionJun 2013
Study completionJun 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Visual ImpairmentStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 244 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01396057
Sponsor's protocol ID: CRFB002EDE17
Other IDs: 2011-001019-30
Acronym: COMRADE-B
Status last verified: Aug 2014
First submitted: 14 Jul 2011
Last updated: 7 Aug 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

Shalchi Z, Mahroo O, Bunce C, Mitry D. Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD009510. doi: 10.1002/14651858.CD009510.pub3.
PubMed 32633861

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 7 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT01396057
Acronym / sponsor ID: COMRADE-B / CRFB002EDE17
Conditions: Visual Impairment, Macular Edema, Branch Retinal Vein Occlusion
Keywords: Visual impairment, macular edema, branch retinal vein occlusion, Dexamethasone implant, Ranibizumab
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 244 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Jul 2011
Primary completion: Jun 2013 (actual)
Study completion: Jun 2013 (actual)
First posted: 18 Jul 2011 (estimated)
Results: Posted 16 Jul 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Ranibizumab	Experimental	Drug: RanibizumabInjections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone	Sham comparator	Other: Dexamethasone Implant, Other: Sham injectionIntravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RanibizumabInjections 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	Drug	Ranibizumab
Dexamethasone ImplantComparator 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.	Other	Dexamethasone
Sham injectionSham 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	Other	Dexamethasone

Primary outcome

Mean Average Best Corrected Visual Acuity (BCVA) Change From Month 1 Through Month 6 to Baseline
Time frame: Baseline, month 6
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

9 secondary outcomes

Mean BCVA Change From Baseline to Endpoints Month 1 to Month 6
Time frame: Baseline, month 6
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment
Time frame: Baseline, 6 month
Time to Achieve a Significant Improvement ≥ 15 Letters
Time frame: Baseline, month 6
Change Over Time in BCVA
Time frame: baseline, month 6
Change Over Time of the Central Retinal Thickness (CRT)
Time frame: Baseline, month 6
Changes in the Quality of Life According to the National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) Questionnaires
Time frame: Baseline, month 6
Changes in the Quality of Life According to the Short Form (36) Health Survey (SF-36)Questionnaires
Time frame: Baseline, month 6
Changes in the Quality of Life According to Euro Quality of Life (EQ-5D) Questionnaires
Time frame: Baseline, month 6
Rate of the Internal Ocular Pressure (IOP)
Time frame: Baseline, month 6

Results and safety

Results posted to the registry on 16 Jul 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ranibizumab	126	115
Dexamethasone	118	100

Primary outcome: Mean Average Best Corrected Visual Acuity (BCVA) Change From Month 1 Through Month 6 to Baseline

Time frame: Baseline, month 6. Mean (Standard Deviation). Unit: Letters

Measure	Ranibizumab n = 126	Dexamethasone n = 118
Value	14.9 (9.9)	10.1 (9.5)

Population analysed: The Full Analysis Set (FAS) consisted of all patients from the Randomized Set (RS) who had received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 2.5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ranibizumab	7 of 126 (5.6%)	71 of 126 (56.3%)	Not reported
Dexamethasone	9 of 118 (7.6%)	89 of 118 (75.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32633861Shalchi Z, Mahroo O, Bunce C, Mitry D. Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD009510. doi: 10.1002/14651858.CD009510.pub3.

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Implementing AI-based Glaucoma Screening Within Federally Qualified Health Centers
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Recruiting
Brain Stimulation Effects on Orientation and Mobility Skills in Adults With Vision Impairment
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

66 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ranibizumab and Dexamethasone Implant in people with Visual Impairment and Macular Edema, run by Novartis Pharmaceuticals at 66 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 66 sites in Germany, United Kingdom, Hungary, Poland, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Average Best Corrected Visual Acuity (BCVA) Change From Month 1 Through Month 6 to Baseline (time frame: Baseline, month 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01396057, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2014.