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. září 2014 aktualizováno: 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.
Přehled studie
Typ studie
Intervenční
Zápis (Aktuální)
373
Fáze
- Fáze 3
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Gent, Belgie, 9000
- Novartis Investigative Site
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Kortrijk, Belgie, 8500
- Novartis Investigative Site
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Leuven, Belgie, 3000
- Novartis Investigative Site
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Bordeaux, Francie, 33 000
- Novartis Investigative Site
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Dijon, Francie, 21034
- Novartis Investigative Site
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Lille, Francie, 59 037
- Novartis Investigative Site
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Limoges Cedex, Francie, 87042
- Novartis Investigative Site
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Lyon, Francie, 69003
- Novartis Investigative Site
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Nantes Cedex 1, Francie, 44093
- Novartis Investigative Site
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Nice, Francie, 6 000
- Novartis Investigative Site
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Paris, Francie, 75015
- Novartis Investigative Site
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Paris cedex 10, Francie, 75475
- Novartis Investigative Site
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Amsterdam, Holandsko, 1081 HV
- Novartis Investigative Site
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Amsterdam, Holandsko, 1105 AZ
- Novartis Investigative Site
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Leiden 2333 ZA, Holandsko, 2333
- Novartis Investigative Site
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Nijmegen, Holandsko, 6525 EX
- Novartis Investigative Site
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Rotterdam, Holandsko, 3011 BH
- Novartis Investigative Site
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Dublin, Irsko
- Novartis Investigative Site
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Dublin 7, Irsko
- Novartis Investigative Site
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Kilkenny, Irsko
- Novartis Investigative Site
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Limerick, Irsko
- Novartis Investigative Site
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FI
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Firenze, FI, Itálie, 50134
- Novartis Investigative Site
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MI
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Milano, MI, Itálie, 20132
- Novartis Investigative Site
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Milano, MI, Itálie, 20122
- Novartis Investigative Site
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Milano, MI, Itálie, 20157
- Novartis Investigative Site
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RM
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Roma, RM, Itálie, 00133
- Novartis Investigative Site
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Roma, RM, Itálie, 00198
- Novartis Investigative Site
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Budapest, Maďarsko, 1083
- Novartis Investigative Site
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Budapest, Maďarsko, 1133
- Novartis Investigative Site
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Debrecen, Maďarsko, 4012
- Novartis Investigative Site
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Gyor, Maďarsko, 9024
- Novartis Investigative Site
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Bielsko-Biala, Polsko, 43-300
- Novartis Investigative Site
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Lublin, Polsko, 20-954
- Novartis Investigative Site
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Warszawa, Polsko, 00-416
- Novartis Investigative Site
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Wroclaw, Polsko, 50-367
- Novartis Investigative Site
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Coimbra, Portugalsko, 3000-354
- Novartis Investigative Site
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Lisboa, Portugalsko, 1150-199
- Novartis Investigative Site
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Porto, Portugalsko, 4099-001
- Novartis Investigative Site
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Aberdeen, Spojené království, AB25 2ZN
- Novartis Investigative Site
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Bristol, Spojené království, BS1 2LX
- Novartis Investigative Site
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Leeds, Spojené království, LS9 7TF
- Novartis Investigative Site
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Manchester, Spojené království, M13 9WL
- Novartis Investigative Site
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Newcastle Upon Tyne, Spojené království, NE1 4LP
- Novartis Investigative Site
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Sheffield, Spojené království, S10 2JF
- Novartis Investigative Site
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Southampton, Spojené království, SO16 6YD
- Novartis Investigative Site
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Sunderland, Spojené království, SR2 9HP
- Novartis Investigative Site
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Wolverhampton, Spojené království, WV10 0QP
- Novartis Investigative Site
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Surrey
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Frimley, Surrey, Spojené království, GU16 7UJ
- Novartis Investigative Site
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Hradec Kralove, Česká republika, 505 05
- Novartis Investigative Site
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Olomouc, Česká republika, 775 20
- Novartis Investigative Site
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Plzen, Česká republika, 301 00
- Novartis Investigative Site
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Prague 2, Česká republika, 128 08
- Novartis Investigative Site
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Praha 6, Česká republika, 169 02
- Novartis Investigative Site
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Athens, Řecko, 152 31
- Novartis Investigative Site
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Thessaloniki, Řecko, 546 36
- Novartis Investigative Site
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Crete
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Heraklion Crete, Crete, Řecko, GR-71110
- Novartis Investigative Site
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Las Palmas de Gran Canaria, Španělsko, 35016
- Novartis Investigative Site
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Madrid, Španělsko, 28040
- Novartis Investigative Site
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Andalucia
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Málaga, Andalucia, Španělsko, 29010
- Novartis Investigative Site
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Castilla y Leon
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Valladolid, Castilla y Leon, Španělsko, 47011
- Novartis Investigative Site
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Cataluña
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L'Hospitalet de Llobregat, Cataluña, Španělsko, 08907
- Novartis Investigative Site
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Comunidad Valenciana
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Alicante, Comunidad Valenciana, Španělsko, 03016
- Novartis Investigative Site
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Valencia, Comunidad Valenciana, Španělsko, 46015
- Novartis Investigative Site
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Galicia
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Santiago de Compostela, Galicia, Španělsko, 15705
- Novartis Investigative Site
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Bern, Švýcarsko, 3010
- Novartis Investigative Site
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Bern, Švýcarsko, 3012
- Novartis Investigative Site
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Binningen, Švýcarsko, 4102
- Novartis Investigative Site
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Zürich, Švýcarsko, 8063
- Novartis Investigative Site
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Singl
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 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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Experimentální: 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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Aktivní komparátor: 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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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: Baseline and 24 month
|
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
Časové okno: 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
Časové okno: Baseline, 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
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Baseline, Month 12 and Month 24
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. září 2010
Primární dokončení (Aktuální)
1. dubna 2013
Dokončení studie (Aktuální)
1. dubna 2013
Termíny zápisu do studia
První předloženo
27. července 2010
První předloženo, které splnilo kritéria kontroly kvality
27. července 2010
První zveřejněno (Odhad)
29. července 2010
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
15. září 2014
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
10. září 2014
Naposledy ověřeno
1. září 2014
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Poruchy metabolismu glukózy
- Metabolické choroby
- Nemoci nervového systému
- Oční nemoci
- Neurologické projevy
- Onemocnění endokrinního systému
- Degenerace sítnice
- Onemocnění sítnice
- Makulární degenerace
- Poruchy vnímání
- Diabetes Mellitus
- Makulární edém
- Otok
- Vize, Nízká
- Poruchy zraku
- Fyziologické účinky léků
- Antineoplastická činidla
- Inhibitory angiogeneze
- Činidla modulující angiogenezi
- Růstové látky
- Inhibitory růstu
- Ranibizumab
Další identifikační čísla studie
- CRFB002D2304
- 2010-019795-74 (Číslo EudraCT)
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .