An oral vitamin A analogue missed its primary endpoint in geographic atrophy

Design

Randomised, double-masked, multicentre, placebo-controlled trial, 24 months (2:1)

Population

198 people aged 60 or older with geographic atrophy

Primary outcome

Geographic atrophy lesion growth rate over 24 months

Effect

1.62 vs 1.87 mm² per year; difference -0.25 (95% CI -0.53 to 0.03; P = 0.075)

This trial was published in June, so it is not new, and is included because geographic atrophy has few options. It randomised 198 people aged 60 or older with geographic atrophy 2:1 to oral gildeuretinol acetate 14 mg a day or placebo for 24 months. About 69% completed.

The primary endpoint, lesion growth, was not met: 1.62 against 1.87 mm² a year (difference -0.25 mm², 95% CI -0.53 to 0.03; P = 0.075), a 13.4% relative reduction. A prespecified analysis allowing for a six-month delay in onset gave a 15.3% reduction (nominal P = 0.047). Low-luminance acuity declined by 3.9 against 8.3 letters (difference 4.4 letters, 95% CI 0.40 to 8.41, nominal P = 0.031). Best-corrected acuity did not differ significantly.

Because the primary endpoint was missed, the secondary and patient-reported findings are exploratory. The authors themselves say they support further trials, not treatment.

• Do not prescribe this agent for geographic atrophy on this evidence.
• Keep counselling on smoking cessation, diet and regular Amsler grid or visual checks.
• Refer to a retina service when the patient asks about trials or approved therapies.
• Treat nominal P values from secondary outcomes as hypotheses.

Why it matters

An oral treatment would change care for a condition where options are limited to injections with modest effect.

Don't overread it

The primary endpoint was not met; secondary and delayed-onset analyses are exploratory.

The statistics, in plain English

When the main test misses, positive secondary results are nominal: they were not adjusted for multiple testing, so some may arise by chance. The 13.4% reduction had an interval that crossed zero.

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