Evaluation of Clonidine Hydrochloride as an Analgesic in Retinopathy of Prematurity Eye Examinations in Premature Infants

The primary objective of this study is to evaluate the efficacy of **clonidine** as an analgesic during eye examinations for Retinopathy of Prematurity (ROP) in premature infants. This is clinically relevant as managing pain effectively during such procedures can improve the overall experience and outcomes for these vulnerable patients.

Secondary objectives include:

• Assessing changes in emotional sweating as measured by Galvanic Skin Response (GSR).
• Evaluating the safety profile of clonidine, focusing on adverse events (AEs), serious adverse events (SAEs), and suspected unexpected serious adverse reactions (SUSARs).
• Determining whether clonidine administration facilitates easier examination by the eye doctor.

The clinical trial focuses on evaluating the efficacy of **clonidine** as an analgesic during eye examinations for **Retinopathy of Prematurity** (ROP) in premature infants. The study population includes both male and female infants born before gestation week 30, admitted to the study clinic, with written consent provided by their guardians. The trial involves a vulnerable population, specifically targeting infants who are at risk of experiencing pain during eye examinations. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the efficacy of **clonidine hydrochloride** as an analgesic during eye examinations for **Retinopathy of Prematurity (ROP)** in premature infants. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias. The trial is expected to span from April 25, 2022, to December 31, 2026, with participant involvement lasting up to two weeks, corresponding to the maximum treatment period of the investigational product.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as admission to the study clinic, written consent from guardians, and birth before gestation week 30. Follow-up visits will be scheduled to monitor the primary endpoint, which involves assessing the Premature Infant Pain Profile-Revised (PIPP-R) scores within 30 seconds after the initiation of the eye examination. Secondary endpoints include galvanic skin response (GSR) metrics, the number of adverse events (AEs), serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), and a visual analog scale (VAS) for examination difficulty.

The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted. Participants may be withdrawn from the study early if they experience significant adverse effects or if the guardian withdraws consent. The trial's methodology and design are structured to ensure the collection of robust data while maintaining participant safety and adherence to ethical standards.

The clinical trial involves the use of **clonidine hydrochloride** as the experimental medication. Clonidine hydrochloride is administered in an oral pharmaceutical form, specifically identified as PHF00082MIG. The medication is provided in a pediatric formulation, suitable for the study population, which consists of premature infants undergoing eye examinations for Retinopathy of Prematurity (ROP). The maximum daily dose of clonidine hydrochloride is 4 mg/ml, with a total maximum dose of 4 mg/ml over the treatment period. The administration is conducted orally, and the treatment period is limited to a maximum of 2 days. Clonidine hydrochloride is classified under the ATC code C02AC01, indicating its role as an antihypertensive agent. The chemical name for clonidine hydrochloride is N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine hydrochloride.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the analgesic efficacy of clonidine hydrochloride during the specified medical procedure. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol, although specific compliance monitoring methods are not detailed in the provided data.

The efficacy of clonidine as an analgesic during eye examinations for **Retinopathy of Prematurity (ROP)** will be assessed using specific endpoints. The primary endpoint is the Premature Infant Pain Profile-Revised (PIPP-R) scores, measured within 30 seconds after the initiation of the eye examination. This assessment occurs when the hooks are in place in the first eye in Uppsala or when the first eye is held open in Örebro. Secondary endpoints include the Galvanic Skin Response (GSR) parameters such as area of small peaks, area of large peaks, peaks per second, and average rise time. Additionally, the number of reported Adverse Events (AEs), Serious Adverse Events (SAEs), and Suspected Unexpected Serious Adverse Reactions (SUSARs) will be recorded. A Visual Analog Scale (VAS) ranging from 0 to 10 cm will also be used, where 0 indicates very easy to examine and 10 indicates very difficult to examine. These efficacy parameters will be collected and analyzed to determine the analgesic effectiveness of clonidine in the specified clinical setting.