Khouri 2019 (ROCKET‐4).

Study characteristics
Methods	Study design: randomized controlled trial Study grouping: parallel group Unit of randomization: participant Total number of participants (eyes) randomized: 708 participants Number of participants (eyes) randomized per group: netarsudil: 351, timolol: 357 participants Total number of participants (eyes) lost to follow‐up: 86 participants Number of participants (eyes) lost to follow‐up per group: netarsudil: 45, timolol: 41 participants Power calculation and sample size consideration reported: yes Planned length of follow‐up: 6 months Actual length of follow‐up: 6 months How missing outcome data were handled: exclusion of participants  Was the trial single/double/triple‐masked: double‐masked (article), quadruple‐masked (NCT) Was the trial an equivalence/superiority/non‐inferiority study: non‐inferiority Extracted outcome results were based on ITT/mITT/CC/PP/PT analysis: PP Duration of washout for each drug class before interventions began: 4 weeks for participants using PAs or BBs prior to study entry, 2 weeks for those using adrenergic agonists, and 5 days for those using muscarinic agonists or topical carbonic anhydrase inhibitors
Participants	Baseline characteristics Netarsudil 0.02%, once per day (p.m.) Female, n (%): 208 (59.3%) Age, mean: 64.1 (SD 11.6) years Age ≥ 65 years, n (%): 186 (53%) POAG, n (%): 223 (63.5%) Time since diagnosis to study entry, mean: 364.1 (SD 367.3) weeks Receiving a glaucoma medication within 30 days of baseline screening, n (%): 221 (63.0%) Number of participants randomized: 351 Number of participants analyzed: 186 (IOP < 25 mmHg) Timolol 0.5%, twice per day Female, n (%): 237 (66.4%) Age, mean: 64.5 (SD 11) years Age ≥ 65 years, n (%): 193 (54.1%) POAG, n (%): 244 (68.3%) Time since diagnosis to study entry, mean: 344.2 (SD 341.1) weeks Receiving a glaucoma medication within 30 days of baseline screening, n (%): 222 (62.2%) Number of participants randomized: 357 Number of participants analyzed: 186 (IOP < 25 mmHg) Overall Female, n (%): 445 (62.9) Age, mean: 64.3 (SD 11.25) years Age ≥ 65 years, n (%): 379 (53.5%) POAG, n (%): 467 (66.0%) Receiving a glaucoma medication within 30 days of baseline screening, n (%): 443 (62.6%) Number of participants randomized: 708 Number of participants analyzed: 372 (IOP < 25 mmHg) Inclusion criteria: aged ≥ 18 years; diagnosis of OAG or OHT in both eyes; post‐washout IOP > 20 mmHg and < 30 mmHg in 1 or both eyes at 2 qualification visits; corrected visual acuity equivalent to 20/200; able to give informed consent and follow study instructions Exclusion criteria: clinically significant ocular disease; pseudoexfoliation or pigment dispersion component glaucoma, history of angle closure or narrow angles; unmedicated IOP ≥ 30 mmHg; 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; ocular trauma within 6 months prior to screening; any ocular surgery or non‐refractive laser treatment within 3 months prior to screening; recent or current ocular infection or inflammation in either eye; used ocular medication in either eye of any type within 30 days of screening; mean central corneal thickness > 620 µm at screening; any abnormality preventing reliable applanation tonometry of either eye; clinically significant abnormalities in laboratory tests at screening; known hypersensitivity or contraindication to BBs; clinically significant systemic disease; participation in any investigational study within 60 days prior to screening; used any systemic medication that could have a substantial effect in IOP within 30 days prior to screening; women who are pregnant, breast‐feeding, planning a pregnancy or not using a medically acceptable form of birth control Pretreatment differences between groups: baseline demographics of randomized participants were similar between the 2 treatment groups Other description of the overall study population at baseline: not reported
Interventions	Netarsudil 0.02%, once per day (p.m.) Timolol 0.5%, twice per day
Outcomes	Primary outcome reported (time points assessed and reported) Mean IOP at 8 a.m., 10 a.m., and 4 p.m. at week 2, week 6 and month 3 in participants with baseline IOP < 25 mmHg Other outcomes reported (time points assessed and reported) Mean IOP at 8 a.m., 10 a.m., and 4 p.m. at week 2, week 6 and month 3 was also examined in participants with baseline IOP < 27 mmHg and in the overall study population (baseline IOP < 30 mmHg) Systemic and ocular safety
Identification	Sponsorship source: Aerie Pharmaceuticals Country: USA Setting: 52 activity sites Online trial registration site: ClinicalTrials.gov Trial registration #: NCT02558374 Phase of the trial (phase 2/phase 3/unclear): phase 3 Current publication reported findings from > 1 trial: no Year of publication accepted: 2019 Year of study initiation (participants screening, enrollment and treatment): 2015
Notes	ROCKET‐4; the citation links to a prior conference abstract whereas the full text was published in Khouri 2019 with a different title.