Clinical trial NCT05387941: Pharmacokinetics and Safety of Dexamethasone Eye Drops in Preterm Infants
Official title: Pharmacokinetics and Safety of Dexamethasone Eye Drops in Preterm Infants With Retinopathy of Prematurity- a Feasibility Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Retinopathy of Prematurity
Keywords: pharmacokinetics
retinopathy of prematurity
dexamethasone
Lead sponsor: Region Skane
Sponsor class: OTHER
First posted: 2022-05-24
Enrollment: 15
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: multicenter interventional phase 1 trial
Primary purpose: TREATMENT

Brief summary: Background and study aims

When an infant is born premature, the blood vessels in the eyes have not developed fully on the retina, and can start to grow incorrectly and result in blindness. To prevent this from happening, premature infants are often screened, and treated with laser or injections into the eye to prevent retinal detachment. A new treatment strategy with steroid eye drops have been found to prevent serious blood vessel growth. The treatment is commonly used in older children and adults to treat different inflammatory conditions, but how the drop is absorbed in premature infants and if there is any risk of side-effects is poorly investigated. The aim of this study is to document how the steroid drop is absorbed and excreted in premature infants and to study if there is a risk of any side effects.

Who can participate?

Premature infants born before gestational age week 30, that undergo eye-screening at Sahlgrenska University Hospital in Gothenburg and Skånes University Hospital in Malmö and Lund or at Helsingborg Hospital, in the need for steroid eye-drop treatment against pathological vessels. It is not possible to participate if the infant has received systemic steroid treatment 2 weeks prior to the eye-drop treatment, or has an ongoing ocular infection.

What does the study involve?

The study involves blood and saliva samples according to a specific protocol designed to be able to learn about the uptake and breakdown of the steroid in premature infants. Measurements of blood pressure, growth and a few urine samples will also be collected during the treatment period usually lasting for some weeks.

At 2.5 and 5 years of age, visual acuity, refractive errors and retinal thickness measurements will be noted.

What are the possible benefits and risks of participating?

The infant will receive steroid eye-drops that have been noted to heavily reduce the number of infants that develop retinal changes that require injections or laser treatment.

The blood samples have been reduced to an absolute minimum in volume and numbers, but will entail some extra samplings from the infant.

The infant will be rigorously checked with regard to any possible side effects from the steroid treatment. Possible but unlikely side effects from the low dose in eye drops are; elevated blood pressure, retarded growth, lowered endogenous steroid production during the eye-drop treatment, increase in blood glucose, and an increase in intra-ocular pressure.


Eligibility criteria: Inclusion Criteria:

* Infants screened for retinopathy of prematurity (ROP) at Sahlgrenska University Hospital in Gothenburg, at Skåne University Hospital in Malmö and Lund and at Helsingborg Hospital.
* zone I stage 1 or 2 ROP without plus disease, posterior zone II stage 2 ROP without plus disease, or zone II stage 3 ROP without plus disease. ROP needs to be documented by digital widefield photography and classification confirmed by two ophthalmologist.

Exclusion Criteria:

* ocular infection
* systemic steroid treatment within two weeks before the start of drop treatment

Primary outcomes:
measure: Pharmacokinetics: half-life of plasma concentrations of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.
timeFrame: up to 14 weeks
measure: Pharmacokinetics: maximum plasma concentration of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.
timeFrame: up to 14 weeks
measure: Pharmacokinetics: saliva koncentrations of dexamethasone during treatment with dexamethasone eye drops.
timeFrame: up to 14 weeks
measure: Pharmacokinetics: saliva koncentrations of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.
timeFrame: up to 14 weeks
measure: Pharmacokinetics: time to reach maximum plasma concentration of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.
timeFrame: up to 14 weeks
measure: Pharmacokinetics: time to reach maximum saliva concentrations of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.
timeFrame: up to 14 weeks
measure: Pharmacokinetics: area under the concentration-time curve for plasma dexamethasone from time point 0 to time t of the last measured concentration above the limit of quantification time.
timeFrame: up to 14 weeks
measure: Pharmacokinetics: area under the concentration-time curve for saliva dexamethasone from time point 0 to time t of the last measured concentration above the limit of quantification time.
timeFrame: up to 14 weeks
measure: Pharmacokinetics: area under the concentration-time curve for plasma dexamethasone from time point 0 to infinity;
timeFrame: up to 14 weeks
measure: Pharmacokinetics: area under the concentration-time curve for saliva dexamethasone from time point 0 to infinity;
timeFrame: up to 14 weeks
measure: Pharmacokinetics: apparent total body clearance
timeFrame: up to 14 weeks
measure: Pharmacokinetics: apparent volume of distribution
timeFrame: up to 14 weeks
measure: Safety: serum concentrations of endogenous corticosteroids before, during and after treatment with dexamethasone eye drops measured with mass spectrometry.
timeFrame: up to 14 weeks
measure: Safety: saliva concentrations of endogenous corticosteroids before, during and after treatment with dexamethasone eye drops.
timeFrame: up to 14 weeks
Secondary outcomes:
measure: To describe if dexamethasone eye drops delay the intervention for type 1 ROP in cases without regression by calculating the time from detection of type 2 ROP to type 1 ROP
timeFrame: Up to 14 weeks
measure: To describe if dexamethasone eye drop treatment before intervention for type 1 ROP reduces the number of recurrences after the intervention.
timeFrame: Up to 14 weeks
measure: To find out if retinal morphology measured with optical coherence tomography is affected by dexamethasone eye drops at 2.5 years of age.
timeFrame: after 2.5 years
measure: To find out if retinal morphology measured with optical coherence tomography is affected by dexamethasone eye drops at 5 years of age.
timeFrame: after 5 years
measure: To find out if dexamethasone eye drops affect visual acuity at 2.5 years of age
timeFrame: after 2.5 years
measure: To find out if dexamethasone eye drops affect refractive errors at 2.5 years of age
timeFrame: after 2.5 years
measure: To find out if dexamethasone eye drops affect visual acuity at 5 years of age
timeFrame: after 5 years
measure: To find out if dexamethasone eye drops affect refractive errors at 5 years of age
timeFrame: after 5 years
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skåne University Hospital
state: Skåne
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
state: Västra Götaland
Study officials:
affiliation: Ophthalmology, dep. of clinical sciences Lund, Lund University, Skåne University Hospital, Sweden
name: Hanna Maria Öhnell, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ophthalmology, inst. of neuroscience and physiology, University of Gothenburg, Sweden
name: Ann Hellström, prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ohnell HM, Andreasson S, Granse L. Dexamethasone Eye Drops for the Treatment of Retinopathy of Prematurity. Ophthalmol Retina. 2022 Feb;6(2):181-182. doi: 10.1016/j.oret.2021.09.002. Epub 2021 Sep 10. No abstract available.