Functional versus functional and anatomical criteria-guided ranibizumab treatment in patients with neovascular age-related macular degeneration – results from the randomized, phase IIIb OCTAVE study

NCT01780935 | OCTAVE Trial | Staurenghi (2020)

Staurenghi G, Garweg JG, Gerendas BS, et al. Functional versus functional and anatomical criteria-guided ranibizumab treatment in patients with neovascular age-related macular degeneration – results from the randomized, phase IIIb OCTAVE study. BMC Ophthalmology, 2020; 20:18.

Locations

92 sites across 24 countries

Study Period

June 2013 – July 2015 (terminated early)

Study Design

Phase IIIb, randomized, double-masked (retreatment criteria only), multicenter comparative trial

Study Population

Characteristic:

Type of AMD:

Wet

AMD Stage:

3 (Late)

Total Sample Size:

671 randomized patients (335 in the VA-guided group, 336 in the VA + OCT-guided group)

Age:

Phase IIIb, randomized, double-masked (retreatment criteria only), multicenter comparative trial

Sex (Male) n%:

264 (39.3%) (derived from group distributions)

Experimental Group

Intervention Therapy:

Ranibizumab 0.5 mg PRN based on BCVA loss and/or OCT-guided disease activity

Dose & Frequency:

Three monthly loading doses, then PRN retreatment based on BCVA loss and/or OCT findings

Age (Years):

75.3 ± 7.9

Number of Patients:

336 randomized and treated

Male N %:

142 (42.3%)

Patients Followed Up:

154 (45.8%)

Control Group

Intervention Therapy:

Ranibizumab 0.5 mg PRN based on BCVA loss alone

Dose & Frequency:

Three monthly loading doses, then PRN retreatment based on BCVA loss criteria only

Age (Years):

73.9 ± 7.9

Number of Patients:

335 randomized and treated

Male N %:

122 (36.4%)

Patients Followed Up:

151 (45.1%)

Follow-up Time: 24 months

Outcomes

Durability

Number of Injections The mean number of injections over 12 months:
• VA + OCT group: 8.4 injections
• VA-only group: 8.2 injections.

Vision

Best-Corrected Visual Acuity (BCVA) Mean change in BCVA (ETDRS letters) at 12 months (primary outcome):
• VA-only group: +8.3 letters (SD 13.53)
• VA+ OCT group: +6.7 letters (SD 13.48). Vision Maintaining The proportion of patients gaining ≥10 ETDRS letters:
• VA + OCT group: 64.9%
• VA-only group: 62.9% The proportion of patients gaining ≥10 ETDRS letters:
• VA + OCT group: 48.1%
• VA-only group: 37.1% The proportion of patients gaining ≥15 ETDRS letters:
• VA + OCT group: 30.5%
• VA-only group: 22.5% The proportion of patients with BCVA ≥73 ETDRS letters at 12 months:
• VA + OCT group: 54.0%
• VA-only group: 49.0%

Other

N/A

Immunognicity

Not reported

Pharmokinetics

Not reported

Anatomic

Central Subfield Thickness (CSFT) The mean reduction in CSFT (µm) at 12 months:
• VA + OCT group: -175.3 (170.45) µm
• VA-only group: -161.3 (163.48) µm

Safety

Ocular AEs Patients with any ocular AEs:
• VA + OCT group: 106 (31.5%)
• VA-only group: 105 (31.4%)
• Common ocular AEs: Conjunctival hemorrhage; IOP increased; Eye pain; Dry eye; VA reduced; Vitreous floaters Non-ocular AEs Patients with any non-ocular AEs:
• VA + OCT group: 143 (42.6%)
• VA-only group: 156 (31.4%)
• Common ocular AEs: Nasopharyngitis; Hypertension; Influenza; Cough; Bronchitis; Osteoarthritis; Arthralgia; Back pain; Urinary tract infection Serious AEs (SAEs) Patients with any ocular SAEs:
• VA + OCT group: 4 (1.2%)
• VA-only group: 2 (0.6%)
• Common ocular AEs: visual acuity (VA) reduced; VA tests abnormal; Choroidal hemorrhage; Encephalitis post varicella; Retinal artery embolism Patients with any non-ocular SAEs:
• VA + OCT group: 43(12.8%)
• VA-only group: 27 (8.1%)
• Common ocular AEs: Osteoarthritis; Syncope; Femoral neck fracture; Lower respiratory tract infection; Atrial fibrillation; Hypertension; Ovarian cyst; Pneumonia Study Discontinuation Patients with study discontinuation due to adverse events:
• VA + OCT group: 4 (1.2%)
• VA-only group: 2 (0.6%) Death
• VA + OCT group: 1
• VA-only group: 1

Outcomes

Conclusion

Both ranibizumab treatment strategies resulted in BCVA and anatomical improvements. VA + OCT-guided retreatment showed a numerical trend toward better outcomes than VA-only retreatment, supporting OCT use in guiding therapy. No new safety concerns were identified.

Risk of Bias Assessment for Primary Outcome

Randomization Process

Low risk
Note: “Eligible patients were randomized (1:1) via Interactive Response Technology…” “Baseline demographic and ocular characteristics were comparable between the treatment groups…”

Missing Outcome Data

Low risk
Note: For the primary outcomes, the data were used for those completed >=12 months. More than half of the patients were not included in the analysis. However, the missingness is due to the early determination, which does not depend on true value.

Selection of the Reported Results

Low risk Note: Registration with protocol

Deviations from Intended Observations

Some concerns Note: This is an open-labeled study. There is no information on whether the deviation arose because of the trial context. The study terminated early. For the 12-month data set analysis, the ITT principle was applied.

Measurement of the Outcome

Low risk Note: “The VA assessor was masked to the retreatment strategy assignment and performed only the BCVA assessment.”

Overall

Some concerns