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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01171976
First received: July 27, 2010
Last updated: September 10, 2014
Last verified: September 2014

July 27, 2010
September 10, 2014
September 2010
April 2013   (final data collection date for primary outcome measure)
Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
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.
Mean change from baseline in Best Corrected Visual Acuity (BCVA) over a 12 month treatment period. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01171976 on ClinicalTrials.gov Archive Site
  • Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 [ Time Frame: Baseline to Month 24 ] [ Designated as safety issue: No ]
    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.
  • Visual Acuity of the Study Eye: Change From Baseline at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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.
  • Visual Acuity of the Study Eye: Change From Baseline at Month 24 [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    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.
  • Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    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.
  • Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 [ Time Frame: Baseline, 24 month ] [ Designated as safety issue: No ]
    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.
  • Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    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.
  • Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 24 [ Time Frame: Baseline and 24 month ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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
  • EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 [ Time Frame: Baseline, Month 12 and Month 24 ] [ Designated as safety issue: No ]
    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
  • Evaluate whether the mean change from baseline in BCVA obtained with either a 0.5 mg ranibizumab TE with adjunctive laser, or with 0.5 mg ranibizumab TE is non-inferior to 0.5 mg ranibizumab PRN [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Demonstrate a stabilizing effect of adjunctive laser, comparing 0.5mg ranibizumab TE with adjunctive laser with 0.5mg ranibizumab TE. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Investigate the efficacy of 0.5 mg ranibizumab TE with adjunctive laser, 0.5 mg ranibizumab TE and 0.5 mg ranibizumab PRN measured by the overall score assessed by VFQ-25 and EQ-5D. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Time course of mean BCVA change from baseline to Month 12, and up to Month 24 obtained with either a 0.5 mg ranibizumab TE with adjunctive laser, or with 0.5 mg ranibizumab TE compared to 0.5 mg ranibizumab PRN. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • To compare the changes in central retinal thickness and central subfield thickness of 0.5 mg ranibizumab TE with adjunctive laser, 0.5 mg ranibizumab TE and 0.5 mg ranibizumab PRN over time. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Diabetic Macular Edema
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 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.
    Intervention: Drug: Ranibizumab
  • Experimental: TE Ranibizumab 0.5 mg alone
    Patients received ranibizumab intravitreal injection therapy only.
    Intervention: Drug: Ranibizumab
  • Active Comparator: PRN Ranibizumab 0.5 mg
    Patients received ranibizumab intravitreal injection therapy as needed according to signs and symptoms of disease.
    Intervention: Drug: Ranibizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
373
April 2013
April 2013   (final data collection date for primary outcome measure)

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

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Ireland,   Belgium,   Czech Republic,   France,   Greece,   Hungary,   United Kingdom,   Italy,   Netherlands,   Poland,   Portugal,   Spain,   Switzerland
 
NCT01171976
CRFB002D2304, 2010-019795-74
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP