Efficacy and Safety of Ranibizumab in Two "Treat and Extend" Treatment Algorithms Versus Ranibizumab As Needed in Patients With Macular Edema and Visual Impairment Secondary to Diabetes Mellitus (RETAIN)

September 10, 2014 updated by: Novartis Pharmaceuticals

A 2 Year Randomized, Single-masked, Multicenter, Controlled Phase IIIb Trial Assessing the Efficacy and Safety of 0.5 mg Ranibizumab in Two "Treat and Extend" Treatment Algorithms vs. 0.5 mg Ranibizumab As Needed in Patients With Macular Edema and Visual Impairment Secondary to Diabetes Mellitus

The purpose of this study is to demonstrate that two investigational treatment regimens have the potential to result in a superior visual acuity improvement as compared to a ranibizumab pro re nata (PRN=as needed) treatment regimen.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
373

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Gent, Belgium, 9000
        • Novartis Investigative Site
      • Kortrijk, Belgium, 8500
        • Novartis Investigative Site
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
  • Czech Republic
      • Hradec Kralove, Czech Republic, 505 05
        • Novartis Investigative Site
      • Olomouc, Czech Republic, 775 20
        • Novartis Investigative Site
      • Plzen, Czech Republic, 301 00
        • Novartis Investigative Site
      • Prague 2, Czech Republic, 128 08
        • Novartis Investigative Site
      • Praha 6, Czech Republic, 169 02
        • Novartis Investigative Site
  • France
      • Bordeaux, France, 33 000
        • Novartis Investigative Site
      • Dijon, France, 21034
        • Novartis Investigative Site
      • Lille, France, 59 037
        • Novartis Investigative Site
      • Limoges Cedex, France, 87042
        • Novartis Investigative Site
      • Lyon, France, 69003
        • Novartis Investigative Site
      • Nantes Cedex 1, France, 44093
        • Novartis Investigative Site
      • Nice, France, 6 000
        • Novartis Investigative Site
      • Paris, France, 75015
        • Novartis Investigative Site
      • Paris cedex 10, France, 75475
        • Novartis Investigative Site
  • Greece
      • Athens, Greece, 152 31
        • Novartis Investigative Site
      • Thessaloniki, Greece, 546 36
        • Novartis Investigative Site
    • Crete
      • Heraklion Crete, Crete, Greece, GR-71110
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, 1083
        • Novartis Investigative Site
      • Budapest, Hungary, 1133
        • Novartis Investigative Site
      • Debrecen, Hungary, 4012
        • Novartis Investigative Site
      • Gyor, Hungary, 9024
        • Novartis Investigative Site
  • Ireland
      • Dublin, Ireland
        • Novartis Investigative Site
      • Dublin 7, Ireland
        • Novartis Investigative Site
      • Kilkenny, Ireland
        • Novartis Investigative Site
      • Limerick, Ireland
        • Novartis Investigative Site
  • Italy
    • FI
      • Firenze, FI, Italy, 50134
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20132
        • Novartis Investigative Site
      • Milano, MI, Italy, 20122
        • Novartis Investigative Site
      • Milano, MI, Italy, 20157
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00133
        • Novartis Investigative Site
      • Roma, RM, Italy, 00198
        • Novartis Investigative Site
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • Novartis Investigative Site
      • Amsterdam, Netherlands, 1105 AZ
        • Novartis Investigative Site
      • Leiden 2333 ZA, Netherlands, 2333
        • Novartis Investigative Site
      • Nijmegen, Netherlands, 6525 EX
        • Novartis Investigative Site
      • Rotterdam, Netherlands, 3011 BH
        • Novartis Investigative Site
  • Poland
      • Bielsko-Biala, Poland, 43-300
        • Novartis Investigative Site
      • Lublin, Poland, 20-954
        • Novartis Investigative Site
      • Warszawa, Poland, 00-416
        • Novartis Investigative Site
      • Wroclaw, Poland, 50-367
        • Novartis Investigative Site
  • Portugal
      • Coimbra, Portugal, 3000-354
        • Novartis Investigative Site
      • Lisboa, Portugal, 1150-199
        • Novartis Investigative Site
      • Porto, Portugal, 4099-001
        • Novartis Investigative Site
  • Spain
      • Las Palmas de Gran Canaria, Spain, 35016
        • Novartis Investigative Site
      • Madrid, Spain, 28040
        • Novartis Investigative Site
    • Andalucia
      • Málaga, Andalucia, Spain, 29010
        • Novartis Investigative Site
    • Castilla y Leon
      • Valladolid, Castilla y Leon, Spain, 47011
        • Novartis Investigative Site
    • Cataluña
      • L'Hospitalet de Llobregat, Cataluña, Spain, 08907
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Alicante, Comunidad Valenciana, Spain, 03016
        • Novartis Investigative Site
      • Valencia, Comunidad Valenciana, Spain, 46015
        • Novartis Investigative Site
    • Galicia
      • Santiago de Compostela, Galicia, Spain, 15705
        • Novartis Investigative Site
  • Switzerland
      • Bern, Switzerland, 3010
        • Novartis Investigative Site
      • Bern, Switzerland, 3012
        • Novartis Investigative Site
      • Binningen, Switzerland, 4102
        • Novartis Investigative Site
      • Zürich, Switzerland, 8063
        • Novartis Investigative Site
  • United Kingdom
      • Aberdeen, United Kingdom, AB25 2ZN
        • Novartis Investigative Site
      • Bristol, United Kingdom, BS1 2LX
        • Novartis Investigative Site
      • Leeds, United Kingdom, LS9 7TF
        • Novartis Investigative Site
      • Manchester, United Kingdom, M13 9WL
        • Novartis Investigative Site
      • Newcastle Upon Tyne, United Kingdom, NE1 4LP
        • Novartis Investigative Site
      • Sheffield, United Kingdom, S10 2JF
        • Novartis Investigative Site
      • Southampton, United Kingdom, SO16 6YD
        • Novartis Investigative Site
      • Sunderland, United Kingdom, SR2 9HP
        • Novartis Investigative Site
      • Wolverhampton, United Kingdom, WV10 0QP
        • Novartis Investigative Site
    • Surrey
      • Frimley, Surrey, United Kingdom, GU16 7UJ
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patient

  • Patients with Type 1 or Type 2 diabetes mellitus (according to American Diabetes Association or World Health Organization [WHO] guidelines) with glycosylated hemoglobin (HbA1c) ≤ 12.0% at screening (Visit 1). Patients should be on diet, exercise, and/or pharmacological treatment for diabetes. Treatment for diabetes must have been stable for at least 3 month.

Ocular

  • Patients with visual impairment due to DME in at least one eye who are eligible for laser treatment in the opinion of the investigator. If both eyes are eligible, the one with the worse visual acuity, as assessed at Visit 1, will be selected by the investigator as the study eye.
  • BCVA ≥ 39 and ≤78 letters in the study eye and, inclusively, using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/160) at screening.
  • Concomitant conditions in the study eye are only permitted if, in the opinion of the investigator, they do not prevent improvement of visual acuity on study treatment.

Exclusion Criteria:

Patient Compliance/ Administrative

  • Pregnant or nursing (lactating) women.

Ocular medical history

  • Active intraocular inflammation (grade trace or above) in either eye at enrollment.
  • Any active infection (e.g. conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) in either eye at the time of enrollment.
  • History of uveitis in either eye at any time.
  • Structural damage within 0.5 disc diameter of the center of the macular in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema.
  • Uncontrolled glaucoma in either eye at screening.

Prior Ocular treatments

  • Panretinal laser photocoagulation in the study eye within 6 months prior to randomization.
  • Focal/grid laser photocoagulation in the study eye within 3 months prior to randomization.
  • Treatment with anti-angiogenic drugs in either eye.

Systemic conditions or treatments

  • History of stroke within 6 months prior to enrollment.
  • Renal failure requiring dialysis.
  • Untreated diabetes mellitus.
  • Blood pressure systolic > 160 mmHg or diastolic > 100 mmHg.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: TE Ranibizumab 0.5 mg and Laser
On Day 1, all patients received an intravitreal injection with 0.5 mg ranibizumab and subsequently entered Phase A which comprised of monthly injections. Laser therapy was applied at Day 1. It could then be re-administered according to ETDRS criteria at any visit with 0.5 mg ranibizumab treatment if deemed necessary by the Treating Investigator with a minimal treatment interval between laser treatments of 3 months. Laser therapy was administered ≥ 30 minutes prior to the ranibizumab injection.
Drug: Ranibizumab
Ranibizumab (Lucentis®) was supplied in vials containing a dose of 0.5 mg/0.05 mL in an aqueous solution (pH 5.5) with histidine, trehalose, and polysorbate 20.
Experimental: TE Ranibizumab 0.5 mg alone
Patients received ranibizumab intravitreal injection therapy only.
Drug: Ranibizumab
Ranibizumab (Lucentis®) was supplied in vials containing a dose of 0.5 mg/0.05 mL in an aqueous solution (pH 5.5) with histidine, trehalose, and polysorbate 20.
Active Comparator: PRN Ranibizumab 0.5 mg
Patients received ranibizumab intravitreal injection therapy as needed according to signs and symptoms of disease.
Drug: Ranibizumab
Ranibizumab (Lucentis®) was supplied in vials containing a dose of 0.5 mg/0.05 mL in an aqueous solution (pH 5.5) with histidine, trehalose, and polysorbate 20.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12
Time Frame: Baseline to Month 12
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Baseline to Month 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24
Time Frame: Baseline to Month 24
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Baseline to Month 24
Visual Acuity of the Study Eye: Change From Baseline at Month 12
Time Frame: Baseline and Month 12
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Baseline and Month 12
Visual Acuity of the Study Eye: Change From Baseline at Month 24
Time Frame: Baseline and Month 24
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Baseline and Month 24
Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12
Time Frame: Baseline, Month 12
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Baseline, Month 12
Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24
Time Frame: Baseline, 24 month
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Baseline, 24 month
Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 12
Time Frame: Baseline, Month 12
High Resolution OCT was performed at every study visit by Spectral Domain OCT (if not available Time Domain OCT was acceptable) and the images were transferred to a digital video disc. These assessments were performed by trained and adequately qualified experts at the sites and prior to any study drug administration. CSFT is the average retinal thickness of the circular area with 1 mm diameter around the foveal center.
Baseline, Month 12
Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 24
Time Frame: Baseline and 24 month
High Resolution OCT was performed at every study visit by Spectral Domain OCT (if not available Time Domain OCT was acceptable) and the images were transferred to a digital video disc. These assessments were performed by trained and adequately qualified experts at the sites and prior to any study drug administration. CSFT is the average retinal thickness of the circular area with 1 mm diameter around the foveal center.
Baseline and 24 month
Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24
Time Frame: Baseline, Month 12 and Month 24
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure the influence of visual disability and symptoms on general health. 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. For each, the patient was asked to rate their condition on a scale of 1-5 or 1-6, where a low number reflects a better outcome. Each response was recoded per the scoring rules outlined in the National Eye Institute (NEI) VFQ-25 Scoring Algorithm. Under this scoring algorithm , the recoded values range between 0 and 100 and a high score means a better functioning
Baseline, Month 12 and Month 24
EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24
Time Frame: Baseline, Month 12 and Month 24
The Euro Quality of Life Questionnaire (EQ-5D) is an indirect utility questionnaire. It is a standardized instrument was utilized to measure health outcomes related to 5 dimensions, namely: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The possible range for each dimension was 1 to 3, where 1= "no problems", 2="some problems" and 3="extreme problems" . A composite health index was then defined by combining the levels for each dimension. Overall, 243 health states are possible. For each health state, the EuroQol group has assigned a utility value typically between 0 and 1 with lower scores representing a higher level of dysfunction
Baseline, Month 12 and Month 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 27, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 27, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 29, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 15, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CRFB002D2304
  • 2010-019795-74 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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