Efficacy and Safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening

Retinopathy of Prematurity Clinical Trial

— MyMiROPS  

Official title:

Efficacy and Safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening: a Non-inferiority Crossover Randomized Controlled Trial (MyMiROPS Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05043077
• Other study ID #: 23265/14-07-2021
• Status: Completed
• Phase: Phase 4
• Start date: September 7, 2021
• Est. completion date: January 23, 2023

Study information

• Verified date: February 2023
• Source: Aristotle University Of Thessaloniki
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: January 23, 2023
• Est. primary completion date: January 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Weeks to 36 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

Drug:
• Microdrop administration of phenylephrine 1.67% and tropicamide 0.33%
1 drop (6.5 µL) for 3 doses with 5-minute intervals
• Standard drop administration of phenylephrine 1.67% and tropicamide 0.33%
1 drop (28-34 µL) for 3 doses with 5-minute intervals

Locations

Country	Name	City	State
Greece	Papageorgiou General Hospital	Thessaloníki

Sponsors (2)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki	National and Kapodistrian University of Athens

Country where clinical trial is conducted

Greece, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mydriatic efficacy: millimeters of horizontal pupil diameter.		45 minutes after the first drop instillation.
Secondary	Mydriasis sustainability: millimeters of horizontal pupil diameter.		90 minutes after the first drop instillation.
Secondary	Mydriasis sustainability: millimeters of horizontal pupil diameter.		120 minutes after the first drop instillation.
Secondary	Pharmacokinetic profile of phenylephrine: area under the whole blood concentration versus time curve (AUC).	Each participant will be sampled once (random allocation to one time-point). Blood sampling will be combined with peripheral blood collection for routine examinations.	Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation.
Secondary	Pharmacokinetic profile of phenylephrine: maximum (peak) whole blood concentration (Cmax).	Each participant will be sampled once (random allocation to one time-point). Blood sampling will be combined with peripheral blood collection for routine examinations.	Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation.
Secondary	Pharmacokinetic profile of phenylephrine: time to reach maximum (peak) whole blood concentration (Tmax).	Each participant will be sampled once (random allocation to one time-point). Blood sampling will be combined with peripheral blood collection for routine examinations.	Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation.
Secondary	Pharmacokinetic profile of phenylephrine: elimination half-life (T1/2).	Each participant will be sampled once (random allocation to one time-point). Blood sampling will be combined with peripheral blood collection for routine examinations.	Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation.
Secondary	Heart rate values (beats per minute).		45, 90 and 120 minutes after the first drop instillation.
Secondary	Oxygen saturation (SpO2) values (%).		45, 90 and 120 minutes after the first drop instillation.
Secondary	Systolic, diastolic, and mean blood pressure values (mmHg).		45, 90 and 120 minutes after the first drop instillation. Hourly blood pressure measurements for the first 24 hours after mydriasis.
Secondary	Number of participants with systemic adverse events.	Apnea, increased gastric residuals, inhibited duodenal motor activity, delayed gastric emptying, feeding intolerance, abdominal distension, vomiting, paralytic ileus, acute gastric dilatation, necrotizing enterocolitis (NEC).	During the 48 hours after mydriasis.
Secondary	Number of participants with local adverse events.	Periorbital pallor, eyelid swelling, flushing.	45 minutes after the first drop instillation.
Secondary	Adequacy of judging the presence or absence of treatment-requiring ROP.		At the end of the eye examination (fundoscopy).