Retinopathy of Prematurity
Conditions
Keywords
microdrops, mydriasis, dilating drops, phenylephrine, tropicamide, retinopathy of prematurity, ROP, 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.
Interventions
DRUGMicrodrop administration of phenylephrine 1.67% and tropicamide 0.33%
1 drop (6.5 μL) for 3 doses with 5-minute intervals
DRUGStandard drop administration of phenylephrine 1.67% and tropicamide 0.33%
1 drop (28-34 μL) for 3 doses with 5-minute intervals
Sponsors
National and Kapodistrian University of Athens
Aristotle University Of Thessaloniki
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SCREENING
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Weeks to 36 Weeks
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mydriatic efficacy: millimeters of horizontal pupil diameter. | 45 minutes after the first drop instillation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profile of phenylephrine: area under the whole blood concentration versus time curve (AUC). | Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation. | Each participant will be sampled once (random allocation to one time-point). Blood sampling will be combined with peripheral blood collection for routine examinations. |
| Pharmacokinetic profile of phenylephrine: maximum (peak) whole blood concentration (Cmax). | Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation. | Each participant will be sampled once (random allocation to one time-point). Blood sampling will be combined with peripheral blood collection for routine examinations. |
| Pharmacokinetic profile of phenylephrine: time to reach maximum (peak) whole blood concentration (Tmax). | Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation. | Each participant will be sampled once (random allocation to one time-point). Blood sampling will be combined with peripheral blood collection for routine examinations. |
| Pharmacokinetic profile of phenylephrine: elimination half-life (T1/2). | Blood sampling at 15, 20, 25, 30, 40, 50, 60, 120, and 180 minutes after the first drop instillation. | Each participant will be sampled once (random allocation to one time-point). Blood sampling will be combined with peripheral blood collection for routine examinations. |
| Heart rate values (beats per minute). | 45, 90 and 120 minutes after the first drop instillation. | — |
| Mydriasis sustainability: millimeters of horizontal pupil diameter. | 90 minutes after the first drop instillation. | — |
| 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. | — |
| Number of participants with systemic adverse events. | During the 48 hours after mydriasis. | Apnea, increased gastric residuals, inhibited duodenal motor activity, delayed gastric emptying, feeding intolerance, abdominal distension, vomiting, paralytic ileus, acute gastric dilatation, necrotizing enterocolitis (NEC). |
| Number of participants with local adverse events. | 45 minutes after the first drop instillation. | Periorbital pallor, eyelid swelling, flushing. |
| Adequacy of judging the presence or absence of treatment-requiring ROP. | At the end of the eye examination (fundoscopy). | — |
| Oxygen saturation (SpO2) values (%). | 45, 90 and 120 minutes after the first drop instillation. | — |
Countries
Greece
Outcome results
None listed