Clonidine as Pain Relief During ROP Eye Examinations (cloROP)

Preterm infants are at risk of developing ROP (retinopathy of prematurity), an eye condition that can cause blindness. Preterm infants born before gestation week (GA) 30 are therefor screened regularly with eye examinations. These eye examinations are painful and despite a lot of research no clear method of pain relief have been found. Since pain in the preterm infant can lead to both short- and longterm negative consequences an effective pain relief during these examinations are of importance. In this study we will investigate if Clonidine can be effective as pain-relief during ROP eye examinations.

Study Overview

• Status: Recruiting
• Conditions: Retinopathy of Prematurity; Pain, Procedural; Premature Infant Disease
• Intervention / Treatment: Drug: Clonidine Oral Liquid Product; Drug: Sterile water

Detailed Description

Infants born before gestational week (GA) 30 who are cared for in neonatal units at the university hospitals in Örebro and Uppsala, Sweden can be included in the study.

According to power calculations 18 infants are needed for a power of 80% and significance level of 0.05 in order to cover for potential dropouts we plan to include 25 infants. Since the eye examinations are performed without eye speculum in Örebro and with eye speculum in Uppsala we plan to include 25 infants at each unit. The patient will be its own control and examined according to the units´ guidelines. Data will be collected during the patients´ first two eye examinations. In order to exclude potential effects of previous pain experience the order of treatment (clonidine/sterile water) will be randomized.

Sixty minutes before the first eye examination the infant will receive Clonidine or sterile water in corresponding volumes in the GI-tube by a nurse. During the examination the infant will be placed on a heated examination table and connected to an oxygen saturation probe (measuring oxygen saturation and heart rate) on one foot and electrodes for Galvanic skin response (GSR) on the other. The ophthalmologist will examine the infants eyes without eye speculum or with eye speculum on the respective unit. The infants face, oxygen saturation and heart rate will be videotaped before, during and after the examination making it possible to perform av PIPP-R pain assessment at a later time.

After the eye examination the ophtalmologist will be asked to estimate hos easy the infant was to examine by putting an "x" somewhere on a 10 centimeter long line where one end signifies "very easy to examine" and the other end signifies "very difficult to examine". The ophtalmologist can also write any other comments regarding the examination on the same form. The same procedure will be repeated during the infants´ second examination, but with the treatment he/she did not receive during the first examination.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Miriam Pettersson, MD, PhD; Phone Number: +46196023491; Email: miriam.pettersson@regionorebrolan.se
• Study Contact Backup: Name: Emma Olsson, RN, PhD; Phone Number: +4619303616; Email: emma.olsson@oru.se

Study Locations

• Sweden
  • Örebro, Sweden
    • Recruiting
    • Barn- och Ungdomskliniken, Universitetssjukhuset
    • Contact: Miriam Pettersson, PhD
    • Contact: Emma Olsson, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 3 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants born before 30 weeks gestation, informed consent from parents

Exclusion Criteria:

• Infants that have received other pain relieving or sedating drugs within 24 hours before the procedure, infants without GI-tube, infants with neurological deficit, infants with known heart arrhythmia, infants with circulatory instability (MAP below GA in weeks)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clonidine with eye speculum; 4 mcg/kg Clonidine given orally in GI-tube.	Drug: Clonidine Oral Liquid Product; Clonidine prepared from pharmacy with 20 mcg/ml concentration.
Placebo Comparator: Placebo with eye speculum; Sterile water corresponding to the same volume as 4 mcg/kg of Clonidine given orally in GI-tube.	Drug: Sterile water; Sterile water used as placebo
Experimental: Clonidine without eye speculum; 4 mcg/kg Clonidine given orally in GI-tube.	Drug: Clonidine Oral Liquid Product; Clonidine prepared from pharmacy with 20 mcg/ml concentration.
Placebo Comparator: Placebo without eye speculum; Sterile water corresponding to the same volume as 4 mcg/kg of Clonidine given orally in GI-tube.	Drug: Sterile water; Sterile water used as placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PIPP-R	Pain assessment scale	Within 30 sec after procedure started

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GSR	Galvanic skin response	Within 30 sec after procedure started

Collaborators and Investigators

• Sponsor: Region Örebro County
• Collaborators: Uppsala County Council, Sweden

Publications and helpful links

General Publications

• Carlsen Misic M, Eriksson M, Normann E, Pettersson M, Blomqvist Y, Olsson E. Clonidine as analgesia during retinopathy of prematurity screening in preterm infants (cloROP): protocol for a randomised controlled trial. BMJ Open. 2022 Sep 22;12(9):e064251. doi: 10.1136/bmjopen-2022-064251.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: May 21, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: retinopathy of prematurity; neonatal; procedural pain
• Additional Relevant MeSH Terms: Eye Diseases; Pain; Neurologic Manifestations; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Retinal Diseases; Premature Birth; Retinopathy of Prematurity; Pain, Procedural; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: 273547

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No