Multicentre, randomised clinical trial comparing intravitreal aflibercept monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) for the treatment of polypoidal choroidal vasculopathy

Abstract

Purpose: To compare the efficacy and safety of intravitreal aflibercept (IVA) monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) (IVA+RF-PDT) for the treatment of polypoidal choroidal vasculopathy (PCV).

Methods and analysis: Multicentred, double-masked, randomised controlled trial to compare the two treatment modalities. The primary outcome of the study is to compare the 52-week visual outcome of IVA versus IVA+RF PDT. One hundred and sixty treatment-naïve patients with macular PCV confirmed on indocyanine green angiography will be recruited from three centres in Singapore. Eligible patients will be randomised (1:1 ratio) into one of the following groups: IVA monotherapy group-aflibercept monotherapy with sham photodynamic therapy (n=80); combination group-aflibercept with RF-PDT (n=80). Following baseline visit, all patients will be monitored at 4 weekly intervals during which disease activity will be assessed based on best-corrected visual acuity (BCVA), ophthalmic examination findings, optical coherence tomography (OCT) and angiography where indicated. Eyes that meet protocol-specified retreatment criteria will receive IVA and sham/RF-PDT according to their randomisation group. Primary endpoint will be assessed as change in BCVA at week 52 from baseline. Secondary endpoints will include anatomical changes based on OCT and dye angiography as well as safety assessment. Additionally, we will be collecting optical coherence tomography angiography data prospectively for exploratory analysis.

Ethics and dissemination: This study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the ICH E6 guidelines of Good Clinical Practice and the applicable regulatory requirements. Approval from the SingHealth Centralised Institutional Review Board has been sought prior to commencement of the study.

Trial registration number: NCT03941587.

Keywords: clinical trials; medical ophthalmology; medical retina.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Randomisation of the patients in the monotherapy or combination therapy groups. Once enrolled, study participants will be randomised to two treatment groups using a ratio of 1:1: (1) combination group: aflibercept combined with RF-PDT, IVA; (2) monotherapy group: aflibercept monotherapy with sham RF-PDT. ICGA, indocyanine green angiography; IVA, intravitreal aflibercept; PCV, polypoidal choroidal vasculopathy; RF-PDT, reduced-fluence photodynamic therapy.

Figure 2

Visit schedules for each randomisation group. RF-PDT/Sham PDT will be administered PRN as per protocol-specific retreatment criteria based on the presence of active polyps on ICGA. Minimum interval between two PDT treatment will be at least 12 weeks. Aflibercept administered PRN as per protocol-specific retreatment criteria. The minimum interval between two aflibercept treatments will be at least 28 days. BCVA, best-corrected visual acuity; ICGA, indocyanine green angiography; OCT, optical coherence tomography; PDT, photodynamic therapy; PRN, pro re nata; RF-PDT, reduced-fluence photodynamic therapy.

Figure 3

Retreatment criteria after baseline treatment. At each study visit, disease activity will be assessed by a masked investigator. Presence or worsening of the disease activity is considered if one or more of the following criteria are present: (1) loss of BCVA≥5 letters from best achieved BCVA since baseline, (2) presence of any amount of intraretinal fluid or any subretinal fluid, and (3) presence of new retinal haemorrhage. Depending on the duration since last the RF-PDT treatment, the patient will be treated either with monotherapy aflibercept (12 weeks since the last RF-PDT). if angiographic analysis suggests polypoidal lesion involving macula with GLD