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

Diabetic Macular Edema Clinical Trial

— RETAIN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01171976
• Other study ID #: CRFB002D2304
• Secondary ID: 2010-019795-74
• Status: Completed
• Phase: Phase 3
• First received: July 27, 2010
• Last updated: September 10, 2014
• Start date: September 2010
• Est. completion date: April 2013

Study information

• Verified date: September 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Agence Fédérale des Médicaments et des Produits de Santé Département R&DCzech Republic: State Institute for Drug ControlFrance: Agence Française de Sécurité Sanitaire des Produits de SantéGreece: Ministry of Health & Social Solidarity, (National Organization for Medicines (EOF))Hungary: National Institute of PharmacyItaly: Agenzia Italiana del FarmacoIreland: Clinical Trials,Reciept and Validation unit, Irish Medicines Board (IMB)Netherlands:Centrale Commissie Mensgebonden OnderzoekPoland: Urzad Rejestracji Produktow LeczniczychPortugal:Instituto Nacional da Farmácia e do MedicamentoSpain: Agencia Española de Medicamentos y Productos SanitariosSwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 373
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetic Macular Edema
• Edema
• Macular Edema

Intervention

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.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Kortrijk
Belgium	Novartis Investigative Site	Leuven
Czech Republic	Novartis Investigative Site	Hradec Kralove
Czech Republic	Novartis Investigative Site	Olomouc
Czech Republic	Novartis Investigative Site	Plzen
Czech Republic	Novartis Investigative Site	Prague 2
Czech Republic	Novartis Investigative Site	Praha 6
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Limoges Cedex
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris cedex 10
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Heraklion Crete	Crete
Greece	Novartis Investigative Site	Thessaloniki
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Gyor
Ireland	Novartis Investigative Site	Dublin
Ireland	Novartis Investigative Site	Dublin 7
Ireland	Novartis Investigative Site	Kilkenny
Ireland	Novartis Investigative Site	Limerick
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Leiden 2333 ZA
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Rotterdam
Poland	Novartis Investigative Site	Bielsko-Biala
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	L'Hospitalet de Llobregat	Cataluña
Spain	Novartis Investigative Site	Las Palmas de Gran Canaria
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Málaga	Andalucia
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valladolid	Castilla y Leon
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Binningen
Switzerland	Novartis Investigative Site	Zürich
United Kingdom	Novartis Investigative Site	Aberdeen
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	Frimley	Surrey
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne
United Kingdom	Novartis Investigative Site	Sheffield
United Kingdom	Novartis Investigative Site	Southampton
United Kingdom	Novartis Investigative Site	Sunderland
United Kingdom	Novartis Investigative Site	Wolverhampton

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Czech Republic,  France,  Greece,  Hungary,  Ireland,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through 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	No
Secondary	Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through 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	No
Secondary	Visual Acuity of the Study Eye: Change From Baseline at 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	No
Secondary	Visual Acuity of the Study Eye: Change From Baseline at 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	No
Secondary	Visual Acuity of the Study Eye: Categorized Change From Baseline at 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	No
Secondary	Visual Acuity of the Study Eye: Categorized Change From Baseline at 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, 24 month	No
Secondary	Central Subfield Thickness of the Study Eye: Percent Change From Baseline at 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	No
Secondary	Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 24	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	No
Secondary	Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at 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	No
Secondary	EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at 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	No