Clinical trial NCT01171976: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetic Macular Edema
Keywords: DME
Diabetic macula edema
RETAIN
ranibizumab
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-07-29
Enrollment: 373
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12
timeFrame: Baseline to Month 12
Secondary outcomes:
measure: Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24
timeFrame: Baseline to Month 24
measure: Visual Acuity of the Study Eye: Change From Baseline at Month 12
timeFrame: Baseline and Month 12
measure: Visual Acuity of the Study Eye: Change From Baseline at Month 24
timeFrame: Baseline and Month 24
measure: Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12
timeFrame: Baseline, Month 12
measure: Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24
timeFrame: Baseline, 24 month
measure: Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 12
timeFrame: Baseline, Month 12
measure: Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 24
timeFrame: Baseline and 24 month
measure: Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24
timeFrame: Baseline, Month 12 and Month 24
measure: EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24
timeFrame: Baseline, Month 12 and Month 24
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Kortrijk
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Hradec Kralove
country: Czech Republic
facility: Novartis Investigative Site
city: Olomouc
country: Czech Republic
facility: Novartis Investigative Site
city: Plzen
country: Czech Republic
facility: Novartis Investigative Site
city: Prague 2
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 6
country: Czech Republic
facility: Novartis Investigative Site
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Dijon
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Limoges Cedex
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Paris cedex 10
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
state: Crete
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Gyor
country: Hungary
facility: Novartis Investigative Site
city: Dublin 7
country: Ireland
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Kilkenny
country: Ireland
facility: Novartis Investigative Site
city: Limerick
country: Ireland
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Leiden 2333 ZA
country: Netherlands
facility: Novartis Investigative Site
city: Nijmegen
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Bielsko-Biala
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Málaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Valladolid
country: Spain
facility: Novartis Investigative Site
state: Castilla y Leon
city: L'Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Las Palmas de Gran Canaria
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Binningen
country: Switzerland
facility: Novartis Investigative Site
city: Zürich
country: Switzerland
facility: Novartis Investigative Site
city: Frimley
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Aberdeen
country: United Kingdom
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
city: Sunderland
country: United Kingdom
facility: Novartis Investigative Site
city: Wolverhampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Prunte C, Fajnkuchen F, Mahmood S, Ricci F, Hatz K, Studnicka J, Bezlyak V, Parikh S, Stubbings WJ, Wenzel A, Figueira J; RETAIN Study Group. Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. Br J Ophthalmol. 2016 Jun;100(6):787-95. doi: 10.1136/bjophthalmol-2015-307249. Epub 2015 Oct 9.