A 24-week, Randomized, Single-masked, Multicenter, Phase IV Study to Compare sysTemic VEGF Levels Following Monthly Intravitreal Injections of 0.5 mg Ranibizumab Versus 2 mg Aflibercept Until Week 24 in Patients With Visual Impairment DuE to Diabetic Macular Edema (TIDE DME).
Overview
- Phase
- Phase 4
- Intervention
- Ranibizumab
- Conditions
- Visual Impairment Due to Diabetic Macular Edema
- Sponsor
- Novartis Pharmaceuticals
- Primary Endpoint
- Area under the curve (AUC) of VEGF-A levels from baseline to week 24
- Status
- Withdrawn
- Last Updated
- 9 years ago
Overview
Brief Summary
The purpose of the study is to compare the effect of intravitreal injections of ranibizumab and aflibercept on systemic VEGF levels in DME patients in a detailed time course.
Detailed Description
The purpose of the study is to compare the effect of monthly intravitreal injections of 0.5 mg ranibizumab and 2.0 mg aflibercept on systemic VEGF levels in patients with visual impairment due to DME over a 24 week period. In addition, the study will also assess the effect on systemic VEGF-A levels when patients are switched from aflibercept to ranibizumab.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Type 1 or Type 2 diabetes mellitus
- •Visual impairment due to DME
- •BCVA of 78 to 24 (20/32-20/320) ETDRS letters
Exclusion Criteria
- •Stroke or myocardial infarction less than 3 months prior to screening.
- •Presence of uncontrolled systolic blood pressure or diastolic blood pressure
- •Renal failure requiring dialysis or renal transplant or renal insufficiency
- •Untreated diabetes mellitus
- •Use of any systemic anti-VEGF drugs within 6 months prior to screening.
- •Use of systemic or inhaled corticosteroids for at least 30 consecutive days within 3 months prior to screening.
- •Women who are pregnant or breast feeding or who are menstruating and capable of becoming pregnant\* and not practicing a medically approved method of contraception
- •For either eye:
- •Any active periocular or ocular infection or inflammation
- •Uncontrolled glaucoma
Arms & Interventions
Group 1
Monthly intravitreal injections of 0.5 mg ranibizumab for six months
Intervention: Ranibizumab
Group 2
Monthly intravitreal injections of 2 mg aflibercept for the initial three months followed by monthly intravitreal injections of 0.5 mg ranibizumab for the next three months.
Intervention: Ranibizumab
Group 2
Monthly intravitreal injections of 2 mg aflibercept for the initial three months followed by monthly intravitreal injections of 0.5 mg ranibizumab for the next three months.
Intervention: Aflibercept
Group 3
Monthly injections of 2 mg aflibercept for six months
Intervention: Aflibercept
Outcomes
Primary Outcomes
Area under the curve (AUC) of VEGF-A levels from baseline to week 24
Time Frame: baseline to week 24
Systemic VEGF-A levels following monthly intravitreal injections of 0.5 mg ranibizumab versus 2 mg aflibercept (Area under the curve) expressed in pg/ml\*days. The AUC will be standardized (=divided) by the individual follow-up time and will be calculated by the trapezoidal rule..
Secondary Outcomes
- Mean Systemic VEGF-A levels in serum for patients in treatment group 1 and treatment group 2 within specific time points(Day 7, Day 15, Week 4, week 8, week 12, week 14, week 16, week 18, week 20, week 24)
- Mean Systemic VEGF-A levels in serum for patients in treatment group 1 and treatment group 3 within specific time points(Day 7, Day 15, Week 4, week 8, week 12, week 14, week 16, week 18, week 20, week 24)
- Proportion of patients reporting ocular and/or systemic adverse events in all the three treatment groups.(From Baseline to Week 24)