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 de setembro de 2014 atualizado por: 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.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
373
Estágio
- Fase 3
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Gent, Bélgica, 9000
- Novartis Investigative Site
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Kortrijk, Bélgica, 8500
- Novartis Investigative Site
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Leuven, Bélgica, 3000
- Novartis Investigative Site
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Las Palmas de Gran Canaria, Espanha, 35016
- Novartis Investigative Site
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Madrid, Espanha, 28040
- Novartis Investigative Site
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Andalucia
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Málaga, Andalucia, Espanha, 29010
- Novartis Investigative Site
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Castilla y Leon
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Valladolid, Castilla y Leon, Espanha, 47011
- Novartis Investigative Site
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Cataluña
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L'Hospitalet de Llobregat, Cataluña, Espanha, 08907
- Novartis Investigative Site
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Comunidad Valenciana
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Alicante, Comunidad Valenciana, Espanha, 03016
- Novartis Investigative Site
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Valencia, Comunidad Valenciana, Espanha, 46015
- Novartis Investigative Site
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Galicia
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Santiago de Compostela, Galicia, Espanha, 15705
- Novartis Investigative Site
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Bordeaux, França, 33 000
- Novartis Investigative Site
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Dijon, França, 21034
- Novartis Investigative Site
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Lille, França, 59 037
- Novartis Investigative Site
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Limoges Cedex, França, 87042
- Novartis Investigative Site
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Lyon, França, 69003
- Novartis Investigative Site
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Nantes Cedex 1, França, 44093
- Novartis Investigative Site
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Nice, França, 6 000
- Novartis Investigative Site
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Paris, França, 75015
- Novartis Investigative Site
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Paris cedex 10, França, 75475
- Novartis Investigative Site
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Athens, Grécia, 152 31
- Novartis Investigative Site
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Thessaloniki, Grécia, 546 36
- Novartis Investigative Site
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Crete
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Heraklion Crete, Crete, Grécia, GR-71110
- Novartis Investigative Site
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Amsterdam, Holanda, 1081 HV
- Novartis Investigative Site
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Amsterdam, Holanda, 1105 AZ
- Novartis Investigative Site
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Leiden 2333 ZA, Holanda, 2333
- Novartis Investigative Site
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Nijmegen, Holanda, 6525 EX
- Novartis Investigative Site
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Rotterdam, Holanda, 3011 BH
- Novartis Investigative Site
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Budapest, Hungria, 1083
- Novartis Investigative Site
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Budapest, Hungria, 1133
- Novartis Investigative Site
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Debrecen, Hungria, 4012
- Novartis Investigative Site
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Gyor, Hungria, 9024
- 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
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FI
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Firenze, FI, Itália, 50134
- Novartis Investigative Site
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MI
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Milano, MI, Itália, 20132
- Novartis Investigative Site
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Milano, MI, Itália, 20122
- Novartis Investigative Site
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Milano, MI, Itália, 20157
- Novartis Investigative Site
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Roma, RM, Itália, 00133
- Novartis Investigative Site
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Roma, RM, Itália, 00198
- Novartis Investigative Site
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Bielsko-Biala, Polônia, 43-300
- Novartis Investigative Site
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Lublin, Polônia, 20-954
- Novartis Investigative Site
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Warszawa, Polônia, 00-416
- Novartis Investigative Site
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Wroclaw, Polônia, 50-367
- Novartis Investigative Site
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Coimbra, Portugal, 3000-354
- Novartis Investigative Site
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Lisboa, Portugal, 1150-199
- Novartis Investigative Site
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Porto, Portugal, 4099-001
- Novartis Investigative Site
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Aberdeen, Reino Unido, AB25 2ZN
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Bristol, Reino Unido, BS1 2LX
- Novartis Investigative Site
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Leeds, Reino Unido, LS9 7TF
- Novartis Investigative Site
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Manchester, Reino Unido, M13 9WL
- Novartis Investigative Site
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Newcastle Upon Tyne, Reino Unido, NE1 4LP
- Novartis Investigative Site
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Sheffield, Reino Unido, S10 2JF
- Novartis Investigative Site
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Southampton, Reino Unido, SO16 6YD
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Sunderland, Reino Unido, SR2 9HP
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Wolverhampton, Reino Unido, WV10 0QP
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Surrey
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Frimley, Surrey, Reino Unido, GU16 7UJ
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Hradec Kralove, República Checa, 505 05
- Novartis Investigative Site
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Olomouc, República Checa, 775 20
- Novartis Investigative Site
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Plzen, República Checa, 301 00
- Novartis Investigative Site
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Prague 2, República Checa, 128 08
- Novartis Investigative Site
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Praha 6, República Checa, 169 02
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Bern, Suíça, 3010
- Novartis Investigative Site
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Bern, Suíça, 3012
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Binningen, Suíça, 4102
- Novartis Investigative Site
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Zürich, Suíça, 8063
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Solteiro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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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.
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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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Experimental: 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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Comparador Ativo: 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de setembro de 2010
Conclusão Primária (Real)
1 de abril de 2013
Conclusão do estudo (Real)
1 de abril de 2013
Datas de inscrição no estudo
Enviado pela primeira vez
27 de julho de 2010
Enviado pela primeira vez que atendeu aos critérios de CQ
27 de julho de 2010
Primeira postagem (Estimativa)
29 de julho de 2010
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
15 de setembro de 2014
Última atualização enviada que atendeu aos critérios de controle de qualidade
10 de setembro de 2014
Última verificação
1 de setembro de 2014
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Distúrbios do Metabolismo da Glicose
- Doenças Metabólicas
- Doenças do Sistema Nervoso
- Doenças oculares
- Manifestações Neurológicas
- Doenças do Sistema Endócrino
- Degeneração Retiniana
- Doenças Retinianas
- Degeneração macular
- Distúrbios da Sensação
- Diabetes Mellitus
- Edema Macular
- Edema
- Visão, Baixa
- Distúrbios da Visão
- Efeitos Fisiológicos das Drogas
- Agentes Antineoplásicos
- Inibidores de angiogênese
- Agentes Moduladores da Angiogênese
- Substâncias de crescimento
- Inibidores de crescimento
- Ranibizumabe
Outros números de identificação do estudo
- CRFB002D2304
- 2010-019795-74 (Número EudraCT)
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .