Trial reportAdvances in therapy2023
Crossover Randomized Study of Pharmacologic Effects of Ripasudil-Brimonidine Fixed-Dose Combination Versus Ripasudil or Brimonidine.
Trial report in Advances in therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- The bidirectional enigma of glaucoma and anxiety: from neuroinflammatory mechanisms to mind-body integrated therapies.Frontiers in psychiatry · 2025Pooled it
- Long-term intraocular pressure-lowering efficacy and safety of ripasudil-brimonidine fixed-dose combination for glaucoma and ocular hypertension: a multicentre, open-label, phase 3 study.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Trial
- Real-world effectiveness and safety of a fixed-dose combination of 0.4% ripasudil and 0.1% brimonidine in the management of uveitic glaucoma.Japanese journal of ophthalmology · 2026Article
- Effects of Ripasudil Hydrochloride Hydrate-Brimonidine Tartrate Fixed-Dose Combination Using Rho Kinase Inhibitor and Alpha2 Adrenergic Receptor Agonist on Aqueous Column in the Episcleral Vein: A Randomized, Double-Masked, Crossover Clinical Trial (ROCK Alpha-Aqua Study).Journal of clinical medicine · 2026Article
- Review
- Rho Kinase (ROCK) Inhibitors in the Treatment of Glaucoma and Glaucoma Surgery: A Systematic Review of Early to Late Phase Clinical Trials.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Rho Kinase Inhibitors in Glaucoma Management: Current Perspectives and Future Directions.Drug design, development and therapy · 2025Review
- The Application of Rho Kinase Inhibitors in the Management of Glaucoma.International journal of molecular sciences · 2024Review
- Effect of a fixed combination of ripasudil and brimonidine on aqueous humor dynamics in mice.Scientific reports · 2024Article
- Review
- Switching to Brimonidine/Ripasudil Fixed Combination from Brimonidine + Ripasudil.Clinical ophthalmology (Auckland, N.Z.) · 2024Article
- Double-Masked, Vehicle-Controlled, Randomized, Phase II Study of the Ocular Hypotensive Activity and Safety of VVN539 Ophthalmic Solution.Ophthalmology scienceArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMultidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The ophthalmic solution of ripasudil-brimonidine fixed-dose combination (RBFC; K-232) is the first treatment combining a Rho kinase inhibitor and an α
methodsThis single-center, prospective, randomized, open-label, blinded endpoint study with 3 × 3 crossover design randomly assigned healthy adult men to three groups (1:1:1) to undergo consecutive 8-day administration phases (with drug-free intervals of at least 5 days). Subjects received twice-daily instillation of RBFC → ripasudil → brimonidine (group A), ripasudil → brimonidine → RBFC (group B), or brimonidine → RBFC → ripasudil (group C). Endpoints included change in IOP, severity of conjunctival hyperemia, corneal endothelial cell morphology, pupil diameter, and pharmacokinetics.
resultsEighteen subjects were assigned in total (six to each group). RBFC significantly reduced IOP from baseline at 1 h post-instillation on days 1 and 8 (12.7 vs. 9.1 and 9.0 mmHg, respectively; both P < 0.001), and provided significantly greater IOP reductions than ripasudil or brimonidine at several time points. The most common adverse drug reaction with all three treatments was mild conjunctival hyperemia, which transiently increased in severity with RBFC or ripasudil, peaking at 15 min post-instillation. In post hoc analyses, conjunctival hyperemia scores were lower with RBFC than with ripasudil at several time points. Transient morphologic changes in corneal endothelial cells occurred for up to several hours with RBFC or ripasudil, but not with brimonidine. Pupil diameter did not change with RBFC.
conclusionRBFC significantly reduced IOP compared with each agent alone. A combination of each agent's pharmacologic profile was observed in that of RBFC.
trial registrationJapan Registry of Clinical Trials; Registration No. jRCT2080225220.
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