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)
10 settembre 2014 aggiornato da: 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.
Panoramica dello studio
Tipo di studio
Interventistico
Iscrizione (Effettivo)
373
Fase
- Fase 3
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Gent, Belgio, 9000
- Novartis Investigative Site
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Kortrijk, Belgio, 8500
- Novartis Investigative Site
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Leuven, Belgio, 3000
- Novartis Investigative Site
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Bordeaux, Francia, 33 000
- Novartis Investigative Site
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Dijon, Francia, 21034
- Novartis Investigative Site
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Lille, Francia, 59 037
- Novartis Investigative Site
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Limoges Cedex, Francia, 87042
- Novartis Investigative Site
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Lyon, Francia, 69003
- Novartis Investigative Site
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Nantes Cedex 1, Francia, 44093
- Novartis Investigative Site
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Nice, Francia, 6 000
- Novartis Investigative Site
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Paris, Francia, 75015
- Novartis Investigative Site
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Paris cedex 10, Francia, 75475
- Novartis Investigative Site
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Athens, Grecia, 152 31
- Novartis Investigative Site
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Thessaloniki, Grecia, 546 36
- Novartis Investigative Site
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Crete
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Heraklion Crete, Crete, Grecia, GR-71110
- Novartis Investigative Site
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Dublin, Irlanda
- Novartis Investigative Site
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Dublin 7, Irlanda
- Novartis Investigative Site
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Kilkenny, Irlanda
- Novartis Investigative Site
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Limerick, Irlanda
- Novartis Investigative Site
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FI
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Firenze, FI, Italia, 50134
- Novartis Investigative Site
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MI
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Milano, MI, Italia, 20132
- Novartis Investigative Site
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Milano, MI, Italia, 20122
- Novartis Investigative Site
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Milano, MI, Italia, 20157
- Novartis Investigative Site
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RM
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Roma, RM, Italia, 00133
- Novartis Investigative Site
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Roma, RM, Italia, 00198
- Novartis Investigative Site
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Amsterdam, Olanda, 1081 HV
- Novartis Investigative Site
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Amsterdam, Olanda, 1105 AZ
- Novartis Investigative Site
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Leiden 2333 ZA, Olanda, 2333
- Novartis Investigative Site
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Nijmegen, Olanda, 6525 EX
- Novartis Investigative Site
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Rotterdam, Olanda, 3011 BH
- Novartis Investigative Site
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Bielsko-Biala, Polonia, 43-300
- Novartis Investigative Site
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Lublin, Polonia, 20-954
- Novartis Investigative Site
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Warszawa, Polonia, 00-416
- Novartis Investigative Site
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Wroclaw, Polonia, 50-367
- Novartis Investigative Site
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Coimbra, Portogallo, 3000-354
- Novartis Investigative Site
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Lisboa, Portogallo, 1150-199
- Novartis Investigative Site
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Porto, Portogallo, 4099-001
- Novartis Investigative Site
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Aberdeen, Regno Unito, AB25 2ZN
- Novartis Investigative Site
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Bristol, Regno Unito, BS1 2LX
- Novartis Investigative Site
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Leeds, Regno Unito, LS9 7TF
- Novartis Investigative Site
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Manchester, Regno Unito, M13 9WL
- Novartis Investigative Site
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Newcastle Upon Tyne, Regno Unito, NE1 4LP
- Novartis Investigative Site
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Sheffield, Regno Unito, S10 2JF
- Novartis Investigative Site
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Southampton, Regno Unito, SO16 6YD
- Novartis Investigative Site
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Sunderland, Regno Unito, SR2 9HP
- Novartis Investigative Site
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Wolverhampton, Regno Unito, WV10 0QP
- Novartis Investigative Site
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Surrey
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Frimley, Surrey, Regno Unito, GU16 7UJ
- Novartis Investigative Site
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Hradec Kralove, Repubblica Ceca, 505 05
- Novartis Investigative Site
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Olomouc, Repubblica Ceca, 775 20
- Novartis Investigative Site
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Plzen, Repubblica Ceca, 301 00
- Novartis Investigative Site
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Prague 2, Repubblica Ceca, 128 08
- Novartis Investigative Site
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Praha 6, Repubblica Ceca, 169 02
- Novartis Investigative Site
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Las Palmas de Gran Canaria, Spagna, 35016
- Novartis Investigative Site
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Madrid, Spagna, 28040
- Novartis Investigative Site
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Andalucia
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Málaga, Andalucia, Spagna, 29010
- Novartis Investigative Site
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Castilla y Leon
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Valladolid, Castilla y Leon, Spagna, 47011
- Novartis Investigative Site
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Cataluña
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L'Hospitalet de Llobregat, Cataluña, Spagna, 08907
- Novartis Investigative Site
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Comunidad Valenciana
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Alicante, Comunidad Valenciana, Spagna, 03016
- Novartis Investigative Site
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Valencia, Comunidad Valenciana, Spagna, 46015
- Novartis Investigative Site
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Galicia
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Santiago de Compostela, Galicia, Spagna, 15705
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Bern, Svizzera, 3010
- Novartis Investigative Site
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Bern, Svizzera, 3012
- Novartis Investigative Site
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Binningen, Svizzera, 4102
- Novartis Investigative Site
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Zürich, Svizzera, 8063
- Novartis Investigative Site
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Budapest, Ungheria, 1083
- Novartis Investigative Site
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Budapest, Ungheria, 1133
- Novartis Investigative Site
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Debrecen, Ungheria, 4012
- Novartis Investigative Site
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Gyor, Ungheria, 9024
- Novartis Investigative Site
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Separare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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.
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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.
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Sperimentale: TE Ranibizumab 0.5 mg alone
Patients received ranibizumab intravitreal injection therapy only.
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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.
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Comparatore attivo: PRN Ranibizumab 0.5 mg
Patients received ranibizumab intravitreal injection therapy as needed according to signs and symptoms of disease.
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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.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12
Lasso di tempo: Baseline to Month 12
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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.
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Baseline to Month 12
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24
Lasso di tempo: Baseline to Month 24
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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.
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Baseline to Month 24
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Visual Acuity of the Study Eye: Change From Baseline at Month 12
Lasso di tempo: Baseline and Month 12
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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.
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Baseline and Month 12
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Visual Acuity of the Study Eye: Change From Baseline at Month 24
Lasso di tempo: Baseline and Month 24
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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.
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Baseline and Month 24
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Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12
Lasso di tempo: Baseline, Month 12
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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.
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Baseline, Month 12
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Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24
Lasso di tempo: Baseline, 24 month
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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.
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Baseline, 24 month
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Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 12
Lasso di tempo: Baseline, Month 12
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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.
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Baseline, Month 12
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Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 24
Lasso di tempo: Baseline and 24 month
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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.
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Baseline and 24 month
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Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24
Lasso di tempo: Baseline, Month 12 and Month 24
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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
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Baseline, Month 12 and Month 24
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EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24
Lasso di tempo: Baseline, Month 12 and Month 24
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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
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Baseline, Month 12 and Month 24
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 settembre 2010
Completamento primario (Effettivo)
1 aprile 2013
Completamento dello studio (Effettivo)
1 aprile 2013
Date di iscrizione allo studio
Primo inviato
27 luglio 2010
Primo inviato che soddisfa i criteri di controllo qualità
27 luglio 2010
Primo Inserito (Stima)
29 luglio 2010
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
15 settembre 2014
Ultimo aggiornamento inviato che soddisfa i criteri QC
10 settembre 2014
Ultimo verificato
1 settembre 2014
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Disturbi del metabolismo del glucosio
- Malattie metaboliche
- Malattie del sistema nervoso
- Malattie degli occhi
- Manifestazioni neurologiche
- Malattie del sistema endocrino
- Degenerazione retinica
- Malattie retiniche
- Degenerazione maculare
- Disturbi della sensibilità
- Diabete mellito
- Edema maculare
- Edema
- Visione, Bassa
- Disturbi della vista
- Effetti fisiologici delle droghe
- Agenti antineoplastici
- Inibitori dell'angiogenesi
- Agenti di modulazione dell'angiogenesi
- Sostanze per la crescita
- Inibitori della crescita
- Ranibizumab
Altri numeri di identificazione dello studio
- CRFB002D2304
- 2010-019795-74 (Numero EudraCT)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .