Protocol for a randomised, double-masked, sham-controlled phase 4 study on the efficacy, safety and tolerability of intravitreal aflibercept monotherapy compared with aflibercept with adjunctive photodynamic therapy in polypoidal choroidal vasculopathy: the ATLANTIC study.
PURPOSE
The purpose of this study is to compare the efficacy and safety of intravitreal aflibercept (IVA) with sham photodynamic therapy (sPDT) versus IVA with verteporfin PDT (vPDT) in a Caucasian population with treatment-naive polypoidal choroidal vasculopathy (PCV), enrolling into a treat and extend (T&E) regimen.


METHODS AND ANALYSIS
Randomised, double-masked, sham-controlled, multicentre phase 4 investigator-driven clinical trial. The primary outcomes are (1) change in best-corrected visual acuity (BCVA) from baseline and (2) polyp regression at week 52, assessed by indocyanine green angiography (ICGA). Fifty patients with treatment-naive PCV will be recruited from Portuguese and Spanish clinical sites. Eligible patients will receive monthly IVA for 3 months (week 0, week 4 and week 8). At week 16, all patients will repeat ICGA and undergo central randomisation (1:1 ratio) into one of the following groups: Group 1-IVA T&E + vPDT; Group 2-IVA T&E + sPDT. PDT will be performed at week 16, week 28 and week 40 in the presence of active polyps. After week 16, the presence of macular fluid on optical coherence tomography will determine the schedule of observations. When present, the interval between visits/injections will decrease 2 weeks (minimum 6 weeks). When not, the interval between visits/injections will increase 2 weeks (maximum 12 weeks). Efficacy will be evaluated based on BCVA, central retinal thickness and polyp regression. Safety parameters will include assessment of intraocular pressure, adverse events and serious adverse events.


ETHICS AND DISSEMINATION
This study was designed and shall be implemented and reported in accordance with the International Conference on Harmonisation (ICH) Harmonised Tripartite Guidelines for Good Clinical Practice, with applicable local regulations and with the ethical principles laid down in the Declaration of Helsinki. The study received approval from Comissão de Ética para a Investigação Clínica and Comité Ético de investigación Clínica del Hospital Universitari de Bellvitge.


TRIAL REGISTRATION NUMBER
This study is registered under the EudraCT number: 2015-001368-20 and the ClinicalTrials.gov Identifier: NCT02495181.
['Marques|João Pedro|JP|http://orcid.org/0000-0002-1014-0483', 'Farinha|Cláudia|C|', 'Costa|Miguel Ângelo|MÂ|', 'Ferrão|Ângela|Â|', 'Nunes|Sandrina|S|', 'Silva|Rufino|R|']
D000368:Aged D002829:Choroid D020256:Choroidal Neovascularization D005260:Female D006801:Humans D058449:Intravitreal Injections D008297:Male D008875:Middle Aged D010778:Photochemotherapy D017319:Photosensitizing Agents D011127:Polyps D011166:Porphyrins D040262:Receptors, Vascular Endothelial Growth Factor D011993:Recombinant Fusion Proteins D012107:Research Design D016896:Treatment Outcome D000077362:Verteporfin D014792:Visual Acuity
clinical trials adverse events clinical pharmacology medical retina ophthalmology protocols & guidelines