The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration - A phase IV randomised clinical trial with ranibizumab

The FLUID study

Jennifer J. Arnold, Caroline M. Markey, Nicol P Kurstjens, Robyn H. Guymer

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

Background: With increasing experience using anti-VEGF therapy for the treatment of neovascular age-related macular degeneration (nAMD), ophthalmologists have shifted away from a "one size fits all" to an "individualised" approach based on disease activity with the aim of achieving a fluid-free retina. The FLUID study investigates the non-inferiority of a Treat and Extend (T&E) protocol of 0.5 mg ranibizumab, which allows treatment extension in the presence of incomplete resolution of sub-retinal fluid (SRF) ≤200 μm at the foveal centre relative to a T&E protocol that requires complete resolution of all retinal fluid (i.e., both SRF and intra-retinal fluid [IRF]) in patients with nAMD. Methods/Design: This 24 month, randomised, phase IV trial has completed recruitment of treatment-naïve patients randomised 1:1 to ranibizumab "intensive" treatment (complete resolution of IRF and SRF) or ranibizumab "relaxed" treatment (resolution of IRF or >200 μm SRF only at foveal centre). Patients in both arms follow a T&E regimen where extension decisions are based upon assessment of lesion activity: loss of ≥5 letters of visual acuity, new haemorrhage, presence of IRF and SRF on an optical coherence tomography (OCT) scan. The determination of SRF is conducted at a reading centre while the assessment of IRF is physician-determined. The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months. Secondary endpoints include the mean change in central retinal thickness (CRT) from baseline to 12 and 24 months, the number of ranibizumab injections administered at 12 and 24 months, and the pharmacogenomic assessment of AMD Gene Consortium-identified single-nucleotide polymorphisms (SNPs) and their association with treatment response. Three hundred and forty seven (347) patients have been recruited by 16 Australian sites within approximately 16 months. A protocol to adjudicate on SRF has been established by the central reading centre and is demonstrating good concordance with investigator assessment. Discussion: This study will provide important insights into retreatment criteria for managing nAMD using a T&E regimen. The current paper describes the clinical rationale for using a less intensive treatment approach using ranibizumab and details of the treatment protocol. Trial registration: Trial registration number: NCT01972789. Date of registration: 24th October 2013.

Original languageEnglish
Article number31
JournalBMC Ophthalmology
Volume16
Issue number1
DOIs
Publication statusPublished - 24 Mar 2016
Externally publishedYes

Keywords

  • Intra-retinal fluid
  • Neovascular AMD
  • Ranibizumab
  • Sub-retinal fluid
  • Treat and extend regimen

Cite this

@article{874c0d18d7c84314a4b115842ceadeb5,
title = "The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration - A phase IV randomised clinical trial with ranibizumab: The FLUID study",
abstract = "Background: With increasing experience using anti-VEGF therapy for the treatment of neovascular age-related macular degeneration (nAMD), ophthalmologists have shifted away from a {"}one size fits all{"} to an {"}individualised{"} approach based on disease activity with the aim of achieving a fluid-free retina. The FLUID study investigates the non-inferiority of a Treat and Extend (T&E) protocol of 0.5 mg ranibizumab, which allows treatment extension in the presence of incomplete resolution of sub-retinal fluid (SRF) ≤200 μm at the foveal centre relative to a T&E protocol that requires complete resolution of all retinal fluid (i.e., both SRF and intra-retinal fluid [IRF]) in patients with nAMD. Methods/Design: This 24 month, randomised, phase IV trial has completed recruitment of treatment-na{\"i}ve patients randomised 1:1 to ranibizumab {"}intensive{"} treatment (complete resolution of IRF and SRF) or ranibizumab {"}relaxed{"} treatment (resolution of IRF or >200 μm SRF only at foveal centre). Patients in both arms follow a T&E regimen where extension decisions are based upon assessment of lesion activity: loss of ≥5 letters of visual acuity, new haemorrhage, presence of IRF and SRF on an optical coherence tomography (OCT) scan. The determination of SRF is conducted at a reading centre while the assessment of IRF is physician-determined. The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months. Secondary endpoints include the mean change in central retinal thickness (CRT) from baseline to 12 and 24 months, the number of ranibizumab injections administered at 12 and 24 months, and the pharmacogenomic assessment of AMD Gene Consortium-identified single-nucleotide polymorphisms (SNPs) and their association with treatment response. Three hundred and forty seven (347) patients have been recruited by 16 Australian sites within approximately 16 months. A protocol to adjudicate on SRF has been established by the central reading centre and is demonstrating good concordance with investigator assessment. Discussion: This study will provide important insights into retreatment criteria for managing nAMD using a T&E regimen. The current paper describes the clinical rationale for using a less intensive treatment approach using ranibizumab and details of the treatment protocol. Trial registration: Trial registration number: NCT01972789. Date of registration: 24th October 2013.",
keywords = "Intra-retinal fluid, Neovascular AMD, Ranibizumab, Sub-retinal fluid, Treat and extend regimen",
author = "Arnold, {Jennifer J.} and Markey, {Caroline M.} and Kurstjens, {Nicol P} and Guymer, {Robyn H.}",
year = "2016",
month = "3",
day = "24",
doi = "10.1186/s12886-016-0207-3",
language = "English",
volume = "16",
journal = "BMC Ophthalmology",
issn = "1471-2415",
publisher = "Springer-Verlag London Ltd.",
number = "1",

}

The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration - A phase IV randomised clinical trial with ranibizumab : The FLUID study. / Arnold, Jennifer J.; Markey, Caroline M.; Kurstjens, Nicol P; Guymer, Robyn H.

In: BMC Ophthalmology, Vol. 16, No. 1, 31, 24.03.2016.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration - A phase IV randomised clinical trial with ranibizumab

T2 - The FLUID study

AU - Arnold, Jennifer J.

AU - Markey, Caroline M.

AU - Kurstjens, Nicol P

AU - Guymer, Robyn H.

PY - 2016/3/24

Y1 - 2016/3/24

N2 - Background: With increasing experience using anti-VEGF therapy for the treatment of neovascular age-related macular degeneration (nAMD), ophthalmologists have shifted away from a "one size fits all" to an "individualised" approach based on disease activity with the aim of achieving a fluid-free retina. The FLUID study investigates the non-inferiority of a Treat and Extend (T&E) protocol of 0.5 mg ranibizumab, which allows treatment extension in the presence of incomplete resolution of sub-retinal fluid (SRF) ≤200 μm at the foveal centre relative to a T&E protocol that requires complete resolution of all retinal fluid (i.e., both SRF and intra-retinal fluid [IRF]) in patients with nAMD. Methods/Design: This 24 month, randomised, phase IV trial has completed recruitment of treatment-naïve patients randomised 1:1 to ranibizumab "intensive" treatment (complete resolution of IRF and SRF) or ranibizumab "relaxed" treatment (resolution of IRF or >200 μm SRF only at foveal centre). Patients in both arms follow a T&E regimen where extension decisions are based upon assessment of lesion activity: loss of ≥5 letters of visual acuity, new haemorrhage, presence of IRF and SRF on an optical coherence tomography (OCT) scan. The determination of SRF is conducted at a reading centre while the assessment of IRF is physician-determined. The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months. Secondary endpoints include the mean change in central retinal thickness (CRT) from baseline to 12 and 24 months, the number of ranibizumab injections administered at 12 and 24 months, and the pharmacogenomic assessment of AMD Gene Consortium-identified single-nucleotide polymorphisms (SNPs) and their association with treatment response. Three hundred and forty seven (347) patients have been recruited by 16 Australian sites within approximately 16 months. A protocol to adjudicate on SRF has been established by the central reading centre and is demonstrating good concordance with investigator assessment. Discussion: This study will provide important insights into retreatment criteria for managing nAMD using a T&E regimen. The current paper describes the clinical rationale for using a less intensive treatment approach using ranibizumab and details of the treatment protocol. Trial registration: Trial registration number: NCT01972789. Date of registration: 24th October 2013.

AB - Background: With increasing experience using anti-VEGF therapy for the treatment of neovascular age-related macular degeneration (nAMD), ophthalmologists have shifted away from a "one size fits all" to an "individualised" approach based on disease activity with the aim of achieving a fluid-free retina. The FLUID study investigates the non-inferiority of a Treat and Extend (T&E) protocol of 0.5 mg ranibizumab, which allows treatment extension in the presence of incomplete resolution of sub-retinal fluid (SRF) ≤200 μm at the foveal centre relative to a T&E protocol that requires complete resolution of all retinal fluid (i.e., both SRF and intra-retinal fluid [IRF]) in patients with nAMD. Methods/Design: This 24 month, randomised, phase IV trial has completed recruitment of treatment-naïve patients randomised 1:1 to ranibizumab "intensive" treatment (complete resolution of IRF and SRF) or ranibizumab "relaxed" treatment (resolution of IRF or >200 μm SRF only at foveal centre). Patients in both arms follow a T&E regimen where extension decisions are based upon assessment of lesion activity: loss of ≥5 letters of visual acuity, new haemorrhage, presence of IRF and SRF on an optical coherence tomography (OCT) scan. The determination of SRF is conducted at a reading centre while the assessment of IRF is physician-determined. The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months. Secondary endpoints include the mean change in central retinal thickness (CRT) from baseline to 12 and 24 months, the number of ranibizumab injections administered at 12 and 24 months, and the pharmacogenomic assessment of AMD Gene Consortium-identified single-nucleotide polymorphisms (SNPs) and their association with treatment response. Three hundred and forty seven (347) patients have been recruited by 16 Australian sites within approximately 16 months. A protocol to adjudicate on SRF has been established by the central reading centre and is demonstrating good concordance with investigator assessment. Discussion: This study will provide important insights into retreatment criteria for managing nAMD using a T&E regimen. The current paper describes the clinical rationale for using a less intensive treatment approach using ranibizumab and details of the treatment protocol. Trial registration: Trial registration number: NCT01972789. Date of registration: 24th October 2013.

KW - Intra-retinal fluid

KW - Neovascular AMD

KW - Ranibizumab

KW - Sub-retinal fluid

KW - Treat and extend regimen

UR - http://www.scopus.com/inward/record.url?scp=84962408693&partnerID=8YFLogxK

U2 - 10.1186/s12886-016-0207-3

DO - 10.1186/s12886-016-0207-3

M3 - Article

VL - 16

JO - BMC Ophthalmology

JF - BMC Ophthalmology

SN - 1471-2415

IS - 1

M1 - 31

ER -