Diabetic RetinopathyPhase 4DIVERSENCT02366468

Study of Efficacy of Ranibizumab in Different Regimens in Patients With Diabetic Macula Edema

A Phase 4 study testing ranibizumab 0.5 mg in people with Diabetic Retinopathy, run by Novartis Pharmaceuticals at 30 sites in Germany.

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

The purpose of this study was to demonstrate that the change of best corrected visual acuity (BCVA) was comparable in patients treated with ranibizumab at the discretion of the investigator vs. treatment according to a standard of care scheme (pro re nata, as needed). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetic Retinopathy
What is being tested?: ranibizumab 0.5 mg
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 135 participants
Where: 30 sitesGermany
Study dates: 23 Feb 2015to 8 Jun 2017
Phase: Phase 4
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 with Type 1 or Type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) ≤ 12.0%
Patients with visual impairment due to DME in at least one eye
BCVA ≥ 24 and ≤ 78 letters in the study eye

Who cannot join

Active intraocular inflammation
Any active infection in either eye at the
Structural damage within 0.5 disc diameter of the center of the macula in the study eye
Uncontrolled glaucoma in either eye at screening
Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

30 sites in 1 country.

City, postcode or hospital

30 sites in 1 country

Germany30 sites

Novartis Investigative Site
Ahaus, 48683
Novartis Investigative Site
Bayreuth, 95444
Novartis Investigative Site
Berlin, 12203
Novartis Investigative Site
Berlin, 14169
Novartis Investigative Site
Bonn, 53127
Novartis Investigative Site
Cologne, 50924
Novartis Investigative Site
Cologne, 50935
Novartis Investigative Site
Dresden, 01067
Novartis Investigative Site
Düsseldorf, 40212
Novartis Investigative Site
Düsseldorf, 40225
Novartis Investigative Site
Freiburg I. Br, 79106
Novartis Investigative Site
Göttingen, 37075
Novartis Investigative Site
Greifswald, 17475
Novartis Investigative Site
Halle, 06114
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Hösbach, 63768
Novartis Investigative Site
Kempten, 87435
Novartis Investigative Site
Leipzig, 04103
Novartis Investigative Site
Lübeck, 23538
Novartis Investigative Site
Ludwigshafen, 67063
Novartis Investigative Site
Magdeburg, 39108
Novartis Investigative Site
Marburg, 35043
Novartis Investigative Site
München, 80333
Novartis Investigative Site
München, 81675
Novartis Investigative Site
Münster, 48145
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Stuttgart, 70174
Novartis Investigative Site
Tübingen, 72076
Novartis Investigative Site
Ulm, 89075
Novartis Investigative Site
Würzburg, 97080

Other trials in Germany

About this study

Official title: A 12-months, Randomized, VA-assessor Blinded, Multicenter, Controlled Phase IV Trial to Investigate Noninferiority of Two Treatment Algorithms (Discretion of the Investigator vs. Pro re Nata) of 0.5 mg Ranibizumab in Patients With Visual Impairment Due to Diabetic Macula Edema

Conditions: Diabetic Retinopathy
Being tested: ranibizumab 0.5 mg
Keywords: Diabetic macular edema, Visual impairment
Medical subject headings: Diabetic Retinopathy, Vision Disorders

What participants receive

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

ranibizumab 0.5 mgDrug
Also called Lucentis
intravitreal injection

Study groups in NCT02366468
Study group	Role	What they receive
Discretion of the investigator (DI)	Experimental	ranibizumab 0.5 mg, after initial monthly treatment until maximum BCVA and no signs or no further change of disease activity, the investigator treated patients at their own discretion. There were no strict recommendations for retreatment or scheduling of upcoming visits. Receives: Drug: ranibizumab 0.5 mg
Pro re nata (PRN)	Active comparator	ranibizumab 0.5 mg, after initial monthly therapy until maximum BCVA and no signs or no further improvement of disease activity, patients were monitored every month and retreated if any signs of disease activity occurred Receives: Drug: ranibizumab 0.5 mg

What is being measured

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

Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12)
BCVA was assessed as letters read using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. The mean average change from baseline was defined as the difference between the average level of BCVA (ETDRS letters) over all post-baseline assessments from Month 1 to Month 12. A positive change represents an improvement in visual acuity
Measured: Baseline, Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

Secondary outcomes (6)

Number of Visits
Mean number of visits during the study
Measured: Baseline to Month 12
Number of Injections
mean number of injections in the study eye during the study
Measured: Baseline to Month 12
Number of Treatment Free Intervals
A treatment-free interval is the interval between the first NO treatment given when the reason for NO treatment given is one of the three stability criteria and the first subsequent YES treatment given after that.
Measured: Baseline to Month 12
Mean Change in Central Subfield Retinal Thickness (CSRT)
Evaluated by central reading center assessing OCT images
Measured: Baseline to Month 12
Mean Change of Foveal Center Point Thickness
Evaluated by central reading center assessing OCT images
Measured: Baseline to Month 12
Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale
Evaluated by central reading center scoring fundus photography
Measured: Baseline to Month 12

Timeline

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

23 Feb 20158 Jun 2017

First posted19 Feb 2015 (estimated)
Study start23 Feb 2015
Primary completion8 Jun 2017
Study completion8 Jun 2017

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.
Other trials for Diabetic RetinopathyStudies 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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 135 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02366468
Sponsor's protocol ID: CRFB002DDE26
Other IDs: 2014-002854-37, 2014
Acronym: DIVERSE
Status last verified: Jan 2019
First submitted: 12 Jan 2015
Last updated: 4 Jan 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

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?

See locations

Recruiting
Implementing AI-based Glaucoma Screening Within Federally Qualified Health Centers
Glaucoma, Ocular Hypertension
Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
Diabetic Macular Edema, Neovascular Age-related Macular Degeneration
Active, not recruitingPhase 2
Long-Term Follow-Up Study of RGX-314 Administered in the Suprachoroidal Space for Participants With and Without Diabetic Retinopathy
Diabetic Retinopathy, DR
Recruiting
To Investigate the Feasibility and Acceptability of Trained Non-medical Professionals Performing Laser Treatment for Proliferative Diabetic Retinopathy (PDR), and the Potential Impact on Service Capacity. Assess Feasibility of Conducting a Full Trial Comparing Trained ECPs With Ophthalmologists
Proliferative Diabetic Retinopathy (PDR)
RecruitingPhase 2
Oral N-Acetylcysteine on Diabetic Macular Edema
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All Diabetic Retinopathy trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 12-months, Randomized, VA-assessor Blinded, Multicenter, Controlled Phase IV Trial to Investigate Noninferiority of Two Treatment Algorithms (Discretion of the Investigator vs. Pro re Nata) of 0.5 mg Ranibizumab in Patients With Visual Impairment Due to Diabetic Macula Edema
ClinicalTrials.gov ID: NCT02366468
Acronym / sponsor ID: DIVERSE / CRFB002DDE26
Conditions: Diabetic Retinopathy
Keywords: Diabetic macular edema, Visual impairment
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 135 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 23 Feb 2015 (actual)
Primary completion: 8 Jun 2017 (actual)
Study completion: 8 Jun 2017 (actual)
First posted: 19 Feb 2015 (estimated)
Results: Posted 4 Jan 2019

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: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Discretion of the investigator (DI)	Experimental	Drug: ranibizumab 0.5 mgranibizumab 0.5 mg, after initial monthly treatment until maximum BCVA and no signs or no further change of disease activity, the investigator treated patients at their own discretion. There were no strict recommendations for retreatment or scheduling of upcoming visits.
Pro re nata (PRN)	Active comparator	Drug: ranibizumab 0.5 mgranibizumab 0.5 mg, after initial monthly therapy until maximum BCVA and no signs or no further improvement of disease activity, patients were monitored every month and retreated if any signs of disease activity occurred

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 with Type 1 or Type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) ≤ 12.0%
Patients with visual impairment due to DME in at least one eye
BCVA ≥ 24 and ≤ 78 letters in the study eye

Key exclusion criteria (5 listed)

Active intraocular inflammation
Any active infection in either eye at the
Structural damage within 0.5 disc diameter of the center of the macula in the study eye
Uncontrolled glaucoma in either eye at screening
Other protocol-defined inclusion/exclusion criteria may apply.

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
ranibizumab 0.5 mgAlso: Lucentisintravitreal injection	Drug	Discretion of the investigator (DI), Pro re nata (PRN)

Primary outcome

Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12)
Time frame: Baseline, Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12
BCVA was assessed as letters read using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. The mean average change from baseline was defined as the difference between the average level of BCVA (ETDRS letters) over all post-baseline assessments from Month 1 to Month 12. A positive change represents an improvement in visual acuity

6 secondary outcomes

Number of Visits
Time frame: Baseline to Month 12
Number of Injections
Time frame: Baseline to Month 12
Number of Treatment Free Intervals
Time frame: Baseline to Month 12
Mean Change in Central Subfield Retinal Thickness (CSRT)
Time frame: Baseline to Month 12
Mean Change of Foveal Center Point Thickness
Time frame: Baseline to Month 12
Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale
Time frame: Baseline to Month 12

Results and safety

Results posted to the registry on 4 Jan 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Discretion of the Investigator (DI)	68	62
Pro re Nata (PRN)	67	58

Primary outcome: Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12)

Time frame: Baseline, Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12. Mean (Standard Deviation). Unit: Letters

Measure	Discretion of the Investigator (DI) n = 67	Pro re Nata (PRN) n = 66
Baseline (Day 1)	67.4 (9.52)	65.1 (9.59)
post baseline average over month 1 to month 12	73.5 (9.50)	73.8 (7.75)
Visit-averaged change from baseline	6.1 (6.54)	8.6 (6.45)

Discretion of the Investigator (DI) vs Pro re Nata (PRN): Median Difference (Final Values): -0.9 (95% CI -3.04 to 1.27), p = 0.002, ANCOVA

Population analysed: FAS - Last Observation Carried Forward (LOCF)

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: From start of study treatment until month 12. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Discretion of the Investigator (DI)	13 of 68 (19.1%)	44 of 68 (64.7%)	1 of 68
Pro re Nata (PRN)	22 of 67 (32.8%)	43 of 67 (64.2%)	2 of 67

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Undecided

Related trials for Diabetic Retinopathy

Recruiting
Implementing AI-based Glaucoma Screening Within Federally Qualified Health Centers
Glaucoma, Ocular Hypertension
Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
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Active, not recruitingPhase 2
Long-Term Follow-Up Study of RGX-314 Administered in the Suprachoroidal Space for Participants With and Without Diabetic Retinopathy
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Recruiting
To Investigate the Feasibility and Acceptability of Trained Non-medical Professionals Performing Laser Treatment for Proliferative Diabetic Retinopathy (PDR), and the Potential Impact on Service Capacity. Assess Feasibility of Conducting a Full Trial Comparing Trained ECPs With Ophthalmologists
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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

30 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing ranibizumab 0.5 mg in people with Diabetic Retinopathy, run by Novartis Pharmaceuticals at 30 sites in Germany.

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 5 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 4 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in Germany. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 4 Jan 2019). 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 Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12) (time frame: Baseline, Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12). 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 NCT02366468.

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 4 Jan 2019.