Sit 2021.

Study characteristics
Methods	Study design: randomized controlled trial Study grouping: parallel group Unit of randomization: eyes Total number of participants (eyes) randomized: 40 eyes Number of participants (eyes) randomized per group: placebo: 20, netarsudil: 20 eyes Total number of participants (eyes) lost to follow‐up: 4 eyes Number of participants (eyes) lost to follow‐up per group: placebo: 2, netarsudil: 2 eyes Power calculation and sample size consideration reported: yes (analysis plan and published study protocol) Planned length of follow‐up: 7 days Actual length of follow‐up: 7 days How missing outcome data were handled: missing data were not imputed Was the trial single/double/triple‐masked: double‐masked Was the trial an equivalence/superiority/non‐inferiority study: superiority Extracted outcome results were based on ITT/mITT/CC/PP/PT analysis: mITT Duration of washout for each drug class before interventions began: ≥ 4 weeks for prostaglandins and BBs, 2 weeks for alfa‐agonists and 5 days for muscarinic agonists and carbonic anhydrase inhibitors
Participants	Baseline characteristics Overall  Female, n (%): 14 (70%) Age, mean: 63 (SD 12.5) years Age ≥ 65 years, n (%): 11 (55%) POAG, n (%): 5 (25%) Number of eyes randomized: 40 Number of eyes analyzed: 36 Inclusion criteria: aged ≥ 18 years; diagnosis of POAG or OHT in both eyes; unmedicated IOP > 20 mmHg and < 30 mmHg in both eyes at first qualification visit; BCVA equivalent to 20/200 Snellen or better; able to give informed consent and follow study instructions Excluded criteria: clinically significant ocular disease; pseudoexfoliation or pigment dispersion component glaucoma, history of angle closure glaucoma, or narrow angles; IOP ≥ 30 mmHg in either eye; difference in IOP between eyes > 4 mmHg at qualification visit; use of > 2 ocular hypotensive medications within 30 days of screening; known hypersensitivity to any component of the formulation; previous glaucoma surgery or refractive surgery; keratorefractive surgery in either eye; report of ocular injury in either eye within the 6 months prior to screening or ocular or non‐refractive surgery within 3 months prior to screening; recent or current ocular infection or inflammation in either eye; use of ocular medication in either eye of any type within 30 days of screening; mean central corneal thickness > 620 μm in either eye; any abnormality preventing reliable applanation tonometry of either eye; lack of suitable episcleral vein prior to performing episcleral venus pressure measurement (applicable to 1 site only). Systemic: clinically significant abnormalities within 6 weeks prior to screening; clinically significant systemic disease; participation in any investigational study within 60 days prior to screening; use of systemic medication that could have an effect on IOP within 30 days prior to screening; women of child‐bearing potential who were pregnant, breast‐feeding, planning a pregnancy or not using a medically acceptable form of birth control Pretreatment differences between groups: irrelevant for within‐person study
Interventions	Placebo, once per day (8–10 a.m.) Netarsudil 0.02% once per day (8–10 a.m.)
Outcomes	Primary outcome reported (time points assessed and reported) Change in mean diurnal trabecular outflow facility on day 8 compared with baseline (day 1) defined as the mean of facility measurements at 1 p.m. and 4 p.m. Other outcomes reported (time points assessed and reported) Effect of study drug on IOP and episcleral venus pressure compared with vehicle Ocular and systemic safety
Identification	Sponsorship source: Aerie Pharmaceuticals Country: USA Setting: multicenter, 2 clinical sites Online trial registration site: ClinicalTrials.gov Trial registration #: NCT03233308 Phase of the trial (phase 2/phase 3/unclear): phase 2 Current publication reported findings from > 1 trial: no Year of publication accepted: 2021 Year of study initiation (participants screening, enrollment and treatment): 2017
Notes	Within‐person study