Clinical trial NCT05043077: Efficacy and Safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening
Official title: Efficacy and Safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening: a Non-inferiority Crossover Randomized Controlled Trial (MyMiROPS Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Retinopathy of Prematurity
Keywords: microdrops
mydriasis
dilating drops
phenylephrine
tropicamide
retinopathy of prematurity
ROP
screening
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
Collaborators: name: National and Kapodistrian University of Athens
First posted: 2021-09-13
Enrollment: 83
Sex: ALL
Minimum age (years): 30
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SCREENING

Brief summary: The purpose is to test the hypothesis that microdrop instillation of combined phenylephrine 1.67% and tropicamide 0.33% eyedrops causes at least equal mydriasis compared with standard drop instillation of the same mydriatic regimen, which constitutes routine care for pupil dilation during retinopathy of prematurity (ROP) screening in our neonatal intensive care unit. Comparison, also, will be made to the subsequent adverse events and the drug concentration in peripheral blood samples.

Detailed description: A non-inferiority, crossover, randomized controlled trial will be conducted for this purpose. Participants will be randomly assigned to receive either a) microdrops on their first and standard drops on their second screening examination a week later (M/S group), or b) standard drops first and microdrops a week later (S/M group). Microdrops (6.5 μL) will be instilled using a calibrated micropipette, while standard drops (28-34 μL) will be instilled directly through the commercially available plastic multi-dose mydriatic dropper bottle.

Eligibility criteria: Inclusion Criteria:

Preterm infants undergoing screening for ROP, i.e.

* infants with GA \< 32 weeks and/or BW \< 1501 grams
* infants of greater GA and BW with comorbidities, e.g. sepsis, prolonged need for oxygen supplementation etc., as recommended by the attending neonatologist

Exclusion Criteria:

* Unstable clinical condition
* Severe cardiovascular disease
* Congenital anomalies
* Clinical syndromes
* Inotropes' intake during the week prior to enrollment
* Traumatic apoptosis of the corneal epithelium
* Corneal ulcer
* Anatomical variations of the anterior segment
* Infants that are outpatients at the commencement of ROP screening

Primary outcomes:
measure: Mydriatic efficacy: millimeters of horizontal pupil diameter.
timeFrame: 45 minutes after the first drop instillation.
Secondary outcomes:
measure: Mydriasis sustainability: millimeters of horizontal pupil diameter.
timeFrame: 90 minutes after the first drop instillation.
measure: Mydriasis sustainability: millimeters of horizontal pupil diameter.
timeFrame: 120 minutes after the first drop instillation.
measure: Pharmacokinetic profile of phenylephrine: area under the whole blood concentration versus time curve (AUC).
timeFrame: Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation.
measure: Pharmacokinetic profile of phenylephrine: maximum (peak) whole blood concentration (Cmax).
timeFrame: Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation.
measure: Pharmacokinetic profile of phenylephrine: time to reach maximum (peak) whole blood concentration (Tmax).
timeFrame: Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation.
measure: Pharmacokinetic profile of phenylephrine: elimination half-life (T1/2).
timeFrame: Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation.
measure: Heart rate values (beats per minute).
timeFrame: 45, 90 and 120 minutes after the first drop instillation.
measure: Oxygen saturation (SpO2) values (%).
timeFrame: 45, 90 and 120 minutes after the first drop instillation.
measure: Systolic, diastolic, and mean blood pressure values (mmHg).
timeFrame: 45, 90 and 120 minutes after the first drop instillation. Hourly blood pressure measurements for the first 24 hours after mydriasis.
measure: Number of participants with systemic adverse events.
timeFrame: During the 48 hours after mydriasis.
measure: Number of participants with local adverse events.
timeFrame: 45 minutes after the first drop instillation.
measure: Adequacy of judging the presence or absence of treatment-requiring ROP.
timeFrame: At the end of the eye examination (fundoscopy).
Other outcomes:
Locations:
city: Thessaloníki
country: Greece
facility: Papageorgiou General Hospital
Study officials:
References:
citation: Lynch MG, Brown RH, Goode SM, Schoenwald RD, Chien DS. Reduction of phenylephrine drop size in infants achieves equal dilation with decreased systemic absorption. Arch Ophthalmol. 1987 Oct;105(10):1364-5. doi: 10.1001/archopht.1987.01060100066027.
citation: Elibol O, Alcelik T, Yuksel N, Caglar Y. The influence of drop size of cyclopentolate, phenylephrine and tropicamide on pupil dilatation and systemic side effects in infants. Acta Ophthalmol Scand. 1997 Apr;75(2):178-80. doi: 10.1111/j.1600-0420.1997.tb00119.x.
citation: Seliniotaki AK, Prousali E, Lithoxopoulou M, Kokkali S, Ziakas N, Soubasi V, Mataftsi A. Alternative mydriasis techniques for retinopathy of prematurity screening. Int Ophthalmol. 2020 Dec;40(12):3613-3619. doi: 10.1007/s10792-020-01542-x. Epub 2020 Aug 9.
citation: Seliniotaki AK, Lithoxopoulou M, Virgiliou C, Gika H, Dokoumetzidis A, Bougioukas KI, Raikos N, Diamanti E, Ziakas N, Haidich AB, Mataftsi A. Efficacy and Safety of Mydriatic Microdrops for Retinopathy of Prematurity Screening: The MyMiROPS Randomized Clinical Trial. JAMA Ophthalmol. 2025 Feb 1;143(2):110-116. doi: 10.1001/jamaophthalmol.2024.5462.
citation: Seliniotaki AK, Haidich AB, Lithoxopoulou M, Gika H, Boutou E, Virgiliou C, Nikolaidou M, Dokoumetzidis A, Raikos N, Diamanti E, Ziakas N, Mataftsi A. Efficacy and safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening (MyMiROPS): study protocol for a non-inferiority crossover randomized controlled trial. Trials. 2022 Apr 15;23(1):322. doi: 10.1186/s13063-022-06243-7.