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
  Purpose

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.


Condition Intervention Phase
Diabetic Macular Edema
Drug: Ranibizumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 373
Study Start Date: September 2010
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01171976

  Show 68 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01171976     History of Changes
Other Study ID Numbers: CRFB002D2304, 2010-019795-74
Study First Received: July 27, 2010
Results First Received: March 31, 2014
Last Updated: September 10, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Agence Fédérale des Médicaments et des Produits de Santé Département R&D
Czech Republic: State Institute for Drug Control
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Greece: Ministry of Health & Social Solidarity, (National Organization for Medicines (EOF))
Hungary: National Institute of Pharmacy
Italy: Agenzia Italiana del Farmaco
Ireland: Clinical Trials,Reciept and Validation unit, Irish Medicines Board (IMB)
Netherlands:Centrale Commissie Mensgebonden Onderzoek
Poland: Urzad Rejestracji Produktow Leczniczych
Portugal:Instituto Nacional da Farmácia e do Medicamento
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
DME
Diabetic macula edema
RETAIN
ranibizumab

Additional relevant MeSH terms:
Diabetes Mellitus
Edema
Macular Edema
Endocrine System Diseases
Eye Diseases
Glucose Metabolism Disorders
Macular Degeneration
Metabolic Diseases
Retinal Degeneration
Retinal Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on October 29, 2014