Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration

NCT02557451 | STAR Study | Gabrielle et al. (2023)

Gabrielle PH, Delyfer MN, Glacet-Bernard A, et al. Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration. Ophthalmology, 2023; 130:947-957.

Locations

13 hospitals in France

Study Period

April 28, 2016 – May 5, 2020

Study Design

Randomized, open-label, multicenter superiority study

Study Population

Characteristic:

Type of AMD:

2 (Wet AMD)

AMD Stage:

3 (Late)

Total Sample Size:

Age:

Randomized, open-label, multicenter superiority study

Sex (Male) n%:

30 (33.7%)

Experimental Group

Intervention Therapy:

Surgical pars plana vitrectomy (PPV) with subretinal tPA and 20% SF6 tamponade

Control Group

Intervention Therapy:

Pneumatic displacement (PD) with intravitreal tPA and SF6 gas injection

Follow-up Time: 6 months

Outcomes

Durability

The Number of Anti-VEGF Injections
• Additional anti-VEGF injections between month 3 and month 6 were administered to 73.3% of patients in the surgery group and 84.1% in the PD group, with no statistically significant differences between treatment groups
• The median number of injections over 6 months was similar between treatment groups (4.0 [IQR, 3.0-4.0] in the surgery group vs. 3.0 [IQR, 2.0-4.0] in the PD group; adjusted β, 0.1 [95% CI, -0.1 to 0.4]; P= 0.334).

Vision

Best-Corrected Visual Acuity (BCVA)
The mean change in BCVA over 3 months (Primary Outcome):
• Surgery: +16.8 letters (95% CI 8.7–24.9)
• PD: +16.4 letters (95% CI 7.1–25.7)
• Difference: 1.9 (95% CI -11.0 to 14.9); p-value: 0.767
The mean change in BCVA over 6 months:
• Surgery: +17.2 letters (95% CI 9.1–25.4)
• PD: +15.4 letters (95% CI 5.7–25.1)
• Difference: 3.3 (95% CI -10.5 to 17.0); p-value: 0.776.

Vision Maintaining
• The percentage of eyes with VA gain or worsening by 10 letters or more or by 15 letters or more remained similar between groups throughout the study

Other

Quality of Life (QoL) NEI-VFQ-25 Composite Score
Vision-related quality of life (NEI-VFQ-25) at 3 months
• Surgery: 54.3 ± 21.4
• PD: 63.6 ± 23.6
• Difference: -0.5 (95% CI -8.3 to 7.2); p-value: 0.888
Vision-related quality of life (NEI-VFQ-25) at 6 months:
• Surgery: 57.5 ± 22.1
• PD: 60.4 ± 24.0
• Difference: 5.7 (95% CI -2.2 to 13.6); p-value: 0.152

Immunognicity

Not reported

Pharmokinetics

Not reported

Anatomic

Not reported

Safety

Ocular AEs
Patients with ≥1 ocular AEs:
• Surgery: 12 (26.7%)
• PD: 12 (27.3%).
Event number of ocular-related AEs:
• Surgery: 18 events (i.e., retinal detachment 4, vitreous hemorrhage 5, cataract 2)
• PD: 15 events (i.e., vitreous hemorrhage 5, cataract 2).
Serious Ocular-Related AEs
Three ocular adverse events were reported as serious, of which none were related to the treatment.
Withdraw
Two patients withdrew from the study because of adverse events: 1 patient because of retinal detachment and 1 patient because of submacular hemorrhage recurrence.
Death
One patient died during the study for a reason unrelated to the treatment.

Outcomes

Conclusion

Surgery for SMH secondary to nAMD did not result in superior visual gain compared to PD over 3 or 6 months. Both treatments led to clinical VA improvement without unexpected safety concerns. This study does not establish equivalence between surgery and PD.

Risk of Bias Assessment for Primary Outcome

Randomization Process

Low risk

Note: “The allocation algorithm was determined by the statistician of the coordination center before the start of the trial (Clinical Investigation CentredClinical Epidemiology/Clinical Trials, Dijon, France).”

Missing Outcome Data

Low risk

Note: the evidence of the results was not biased by the missingness (sensitivity analysis): “Similar results were observed in the per-protocol analysis …”

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 deviations arose because of the trial context. “The main analysis was performed according to the intention-to-treat principle”

Measurement of the Outcome

Low risk Note: “Visual acuity was assessed by a masked experienced orthoptist at each site with certified equipment. Multimodal imaging was acquired and graded by an independent centralized masked trial investigator.”

Overall

Some concerns