Pharmacokinetics and Safety of Dexamethasone Eye Drops in Preterm Infants

NCT05387941 | Completed Phase 1

• 2 other identifiers: 2022-00536-012020-004933-19
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

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.

Conditions

Retinopathy of Prematurity

Keywords

pharmacokinetics; retinopathy of prematurity; dexamethasone

Outcome Measures

Primary Outcomes (14)

• Pharmacokinetics: half-life of plasma concentrations of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.

  Half-life of dexamethasone- t½, hours

  up to 14 weeks

• Pharmacokinetics: maximum plasma concentration of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.

  Maximum plasma concentration- Cmax, nmol/L

  up to 14 weeks

• Pharmacokinetics: saliva koncentrations of dexamethasone during treatment with dexamethasone eye drops.

  Half-life of dexamethasone- t½, hours

  up to 14 weeks

• Pharmacokinetics: saliva koncentrations of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.

  Maximum saliva concentration- Cmax, nmol/L

  up to 14 weeks

• Pharmacokinetics: time to reach maximum plasma concentration of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.

  tmax, hours

  up to 14 weeks

• Pharmacokinetics: time to reach maximum saliva concentrations of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.

  tmax, hours

  up to 14 weeks

• 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.

  AUC0-t, nmol.h/L

  up to 14 weeks

• 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.

  AUC0-t, nmol.h/L

  up to 14 weeks

• Pharmacokinetics: area under the concentration-time curve for plasma dexamethasone from time point 0 to infinity;

  AUC0-∞, nmol.h/L

  up to 14 weeks

• Pharmacokinetics: area under the concentration-time curve for saliva dexamethasone from time point 0 to infinity;

  AUC0-∞, nmol.h/L

  up to 14 weeks

• Pharmacokinetics: apparent total body clearance

  CL/F, L/h

  up to 14 weeks

• Pharmacokinetics: apparent volume of distribution

  Vz/F, L

  up to 14 weeks

• Safety: serum concentrations of endogenous corticosteroids before, during and after treatment with dexamethasone eye drops measured with mass spectrometry.

  Endogenous levels of corticosteroids, nmol/L

  up to 14 weeks

• Safety: saliva concentrations of endogenous corticosteroids before, during and after treatment with dexamethasone eye drops.

  Endogenous levels of corticosteroids, nmol/L

  up to 14 weeks

Secondary Outcomes (8)

• 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

  Up to 14 weeks

• To describe if dexamethasone eye drop treatment before intervention for type 1 ROP reduces the number of recurrences after the intervention.

  Up to 14 weeks

• To find out if retinal morphology measured with optical coherence tomography is affected by dexamethasone eye drops at 2.5 years of age.

  after 2.5 years

• To find out if retinal morphology measured with optical coherence tomography is affected by dexamethasone eye drops at 5 years of age.

  after 5 years

• To find out if dexamethasone eye drops affect visual acuity at 2.5 years of age

  after 2.5 years

Study Arms (1)

Dexamethasone treated infants

EXPERIMENTAL

15 infants that receive dexamethasone eye drops for treatment of retinopathy of prematurity will be included, and both serum and saliva samples will be collected in order to find out the pharmacokinetic properties of dexamethasone in eye drops according to a pre-specified sampling scheme specifically designed for this purpose by experts in pediatric pharmacokinetics.

Drug: Dexamethasone Ophthalmic

Interventions

Dexamethasone Ophthalmic DRUG

one drop daily in each eye with retinopathy of prematurity of a predefined stage.

Also known as: dexafree

Dexamethasone treated infants

Eligibility Criteria

• Age: Up to 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Region Skane: lead

Study Sites (2)

Skåne University Hospital

Lund, Skåne County, 22185, Sweden

Location

Sahlgrenska University Hospital

Gothenburg, Västra Götaland County, 41685, Sweden

Location

Related Publications (1)

• 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.

  PMID: 34517147 BACKGROUND

MeSH Terms

Conditions

Retinopathy of Prematurity

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Hanna Maria Öhnell, PhD

  Ophthalmology, dep. of clinical sciences Lund, Lund University, Skåne University Hospital, Sweden

  PRINCIPAL INVESTIGATOR

• Ann Hellström, prof

  Ophthalmology, inst. of neuroscience and physiology, University of Gothenburg, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: multicenter interventional phase 1 trial

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: May 24, 2022
• Study Start: June 14, 2022
• Primary Completion: March 4, 2026
• Study Completion: March 4, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)