Abstract
Introduction
Peripheral intravenous cannulation (PIVC) is one of the most frequently performed procedures in paediatric emergency and hospital settings and is often associated with significant pain and anxiety in children. Non-pharmacological interventions may complement standard pain management strategies. This trial will evaluate the effectiveness of PARO, an interactive therapeutic robot, in reducing pain and anxiety during PIVC in children. The study aims to provide clinically relevant evidence to support the integration of socially assistive robots into paediatric pain management.
Methods and analysis
This will be an open-label, multicentre, randomised controlled superiority trial conducted in five paediatric centres in France. A total of 120 children aged 12 months to 7 years requiring PIVC will be randomly assigned (1:1) to receive either standard pain management alone or standard pain management plus the PARO robot during the procedure. Randomisation will be stratified by age and centre using a centralised electronic system. Due to the nature of the intervention, blinding of participants and outcome assessors will not be feasible.
The primary outcome will be the change in pain intensity assessed using the Face, Legs, Activity, Cry, Consolability scale between baseline (15 min before the procedure) and the time of cannulation. Secondary outcomes will include children’s distress assessed using the Procedural Restraint Intensity in Children scale, changes in heart rate, number of attempts required for successful cannulation, parental anxiety assessed using the State Trait Anxiety Inventory questionnaire, parental satisfaction and healthcare professional satisfaction. Statistical analysis will be performed on an intention-to-treat basis using analysis of covariance adjusted for stratification factors, with results reported as effect estimates with 95% CIs.
Ethics and dissemination
The study has received approval from the French National Agency for Medicines and Health Products Safety and the French Committee for the Protection of Personal Data (CPP Ouest I Tours) on 3 July 2025 (No. 25.02471.000436) and is registered at ClinicalTrials.gov (NCT07299006). Results will be disseminated through publication in peer-reviewed journals, presentation at national and international conferences, and communication to healthcare professionals, stakeholders and participants.
Trial registration number
Keywords: Pain management, Artificial Intelligence, Child
Strengths and limitations of this study.
Multicentre randomised controlled superiority design with stratified allocation with clearly defined eligibility and exclusion criteria ensuring population homogeneity.
Use of validated observational scales (Face, Legs, Activity, Cry, Consolability, Procedural Restraint Intensity in Children) for outcome assessment.
Potential variability in standard pain management practices across centres.
Open-label design with no blinding of participants or outcome assessors.
Higher cost of the PARO device compared with standard pain management.
Introduction
Peripheral intravenous cannulation (PIVC) is one of the most frequently performed procedures in paediatric medicine.1 Although common, it is often difficult to perform in children with failure rates reaching up to 53% on the first attempt, potentially leading to negative consequences for future procedures.1 It is also considered to be one of the most painful medical interventions in children2 and is associated with significant anxiety for the child, the parents, and the healthcare team. Pain and anxiety may have short- and long-term consequences on the child’s medical experience and care3 4 including negative cognitive conditioning related to pain memory formation.5 Therefore, reducing distress and anxiety during painful procedures such as needle insertion remains a major clinical challenge.6 Pharmacological approaches, including topical anaesthetics such as Eutectic Mixture of Local Anaesthetics (EMLA) and inhalation of an equimolar nitrous oxide–oxygen mixture (MEOPA), have demonstrated efficacy in reducing procedural pain.7 However, these treatments may have contraindications and side effects8 9 and are often insufficient to address anxiety and fear when used alone. As a result, current recommendations support a multimodal approach combining pharmacological and non-pharmacological interventions.
Non-pharmacological therapies have been shown to be effective in managing healthcare-related pain without causing iatrogenic side effects.10–12 The mechanisms and benefits of these interventions are supported by the ‘Gate Theory of Pain’ developed by Melzack and Wall.13 Moreover, studies have shown the no-superiority of pharmacological interventions over non-pharmacological techniques in pain control in children requiring needle insertion.14 15 Therefore, a multimodal strategy integrating both pharmacological and non-pharmacological modalities should be more effective than relying on pharmacological treatment alone. Non-pharmacological techniques include distraction methods such as screen-distraction16 or listening to music.17 Animal therapy has also been shown to reduce pain and stress based on the positive aspects of the relationship between humans and animals.18 19 In addition, other approaches such as vapocoolant sprays have also demonstrated efficacy in reducing pain associated with venipuncture in children.20 Despite these approaches, effective strategies to reduce both pain and anxiety remain limited. Recently, socially assistive robots have emerged as a novel non-pharmacological intervention, allowing interaction through play, movement and touch in children.21 Several recent reviews have described the use of these robots and suggest a promising role in reducing pain and anxiety in children,22 23 particularly during painful or stressful procedures.24 25
PARO is an interactive therapeutic robot designed to simulate animal-assisted therapy. It has been shown to improve emotional well-being, social engagement and interaction in various populations26–29 including children with neurodevelopmental disorders.30 However, to our knowledge, its effectiveness in reducing pain and anxiety during painful procedures in children has not yet been investigated.
Methods and analysis
Study aim
The aim of this study will be to assess whether a multimodal approach incorporating PARO improves pain management in children during PIVC compared with standard pain management combining pharmacological and non-pharmacological interventions. We hypothesise that children in the PARO group will have a significantly lower increase in Face, Legs, Activity, Cry, Consolability (FLACC) score compared with standard pain management.
Study design
This will be an open-label, prospective, multicentre, randomised controlled superiority trial with a control group, reported in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2025 statement.31 It will be conducted across five paediatric emergency departments and paediatric units in France, including the University Hospital Centres of Nice Lenval and Nice L'Archet, Grasse Hospital, Toulouse and the University Hospital of Brest. Participant recruitment started on 3 March 2026. Primary completion and study completion are both anticipated on 30 March 2027. The eligibility and exclusion criteria are presented in table 1.
Table 1. Eligibility and exclusion criteria.
Inclusion criteria
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Exclusion criteria
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Randomisation, allocation concealment and blinding
Eligible participants and their parents or legal guardians will be provided written information about the trial and asked to sign an informed consent form. An example of the participant consent form is provided in online supplemental material. After obtaining consent, the participants will be randomly assigned to one of two groups (figure 1):
Figure 1. Flow chart of the study. *Participant numbers (n = ***) are not yet available as this is a study protocol. IIT, intention-to-treat.
Group 1 (Control): Standard multimodal pain management as described above.
Group 2 (Intervention): Standard multimodal pain management plus the use of the PARO robot during the procedure.
Randomisation will be carried out by the investigator, a clinical research assistant (CRA) dedicated to the study, or by any physician on duty trained in the use of PARO and the inclusion software. The investigator responsible for inclusion will log into the electronic case report form (e-CRF) system developed using REDCap software and open a new patient file. The patient’s inclusion number and allocation group (via the integrated randomisation module in REDCap) will be automatically generated and sent by email. Investigators have no access to the randomisation sequence or block structure, and the system’s audit trail prevents any modification or anticipation of allocations. Balanced (1:1) randomisation (randomly mixed block sizes) will be carried out by the Delegation of Clinical Research and Innovation (DRCI) at Nice University Hospital using Nquery Advisor V.7.0 software. The randomisation will be stratified on the age (<2 years or ≥2 years) and on the centre (with or without emergency departments). Given the nature of our intervention, blinding of the child, parent or outcome assessor will not be possible.
Intervention and comparator
The intervention and comparator are described in sufficient detail to allow replication, in accordance with the Template for Intervention Description and Replication checklist.32 Standard multimodal pain management includes the use of pharmacological treatments such as topical anaesthetics (EMLA) and/or inhalation of an MEOPA, combined with non-pharmacological approaches according to local clinical practice (screen distraction or listening to music). If the child is randomised to the PARO group, PARO will be placed next to or on the child’s lap approximately 15 min before the procedure to allow the child to become familiar with it. In addition to PARO, the child will receive standard multimodal pain management, including EMLA cream and/or MEOPA, according to local clinical practice. The child may also receive screen distraction or listen to music, depending on the child’s preferences and local clinical practice. If the child is randomised to the standard multimodal pain management group, the child will receive the same standard multimodal pain management, including EMLA cream and/or MEOPA, according to local clinical practice. The child may also receive screen distraction or listen to music, depending on the child’s preferences and local clinical practice. No interaction with PARO will be provided.
PARO is an interactive therapeutic robot designed to simulate animal-assisted therapy. It is covered with synthetic, bactericidal fur containing embedded sensors that enable it to respond to the child’s interaction. The robot will be disinfected after each use using specific cleaning wipes. If necessary, the fur covering PARO can be removed and washed according to the manufacturer’s instructions. Healthcare professionals involved in the study will receive standardised training on the use of PARO to ensure consistency in its implementation across centres. The intervention will be discontinued at any time at the request of the child, parent or healthcare provider, or if considered clinically necessary.
Recruitment and data collection
As the REDCap software is accessible 24 hours a day, 7 days a week, the presence of the CRA will not be systematically required to include children, allowing a longer inclusion time and reflecting real-life conditions. Recruitment will be facilitated by the involvement of multiple centres and departments. Physicians working on the study will be trained to use the software to include eligible children as soon as they meet all the criteria and after obtaining informed consent from the legal representative or one of the two parents. The investigator responsible for inclusion will collect the child’s demographic characteristics (age and sex), history of chronic disease, the reason for consultation and history of emergency room/hospital admission, and whether the child has ever needed PIVC before. The children in the intervention group will be presented with PARO 15 min before the start of the procedure to allow the child to familiarise themselves with it. Skin disinfection and identification of a suitable venous access site will be performed before cannulation. For the purposes of the study, the start of the PIVC procedure is defined as the first attempt to puncture the skin. The procedure will conclude with needle removal and application of a bandage. Once the parents’ satisfaction is assessed, participation in the study ends and follow-up resumes. The patient will then receive standard clinical care. Although the intervention is considered low risk, any adverse events potentially related to the use of PARO (eg, distress, refusal or unexpected reactions) will be recorded and reported. Serious adverse events will be managed according to institutional procedures and reported to the sponsor and relevant authorities if required.
Given the open-label design, a risk of observer bias cannot be excluded, particularly due to the behavioural nature of the FLACC scale. To minimise this risk, outcome assessors will receive standardised training in the use of the FLACC scale.
Primary endpoint measure
The primary outcome is pain intensity during the PIVC. The effectiveness of PARO in reducing pain will be assessed using the evolution in FLACC score (online supplemental appendix 1) between the first attempt to puncture the skin and baseline.33 The FLACC is a validated observer-rated tool used to evaluate pain in children aged between 12 months and 7 years old, particularly for immediate postoperative pain and for brief pain associated with medical procedures.34 This scale assesses five behavioural parameters: facial expression, leg movement, activity, crying and consolability. Each parameter is scored from 0 to 2, resulting in a total score ranging from 0 to 10. A score of 0 indicates a relaxed and comfortable child, while scores between 7 and 10 reflect severe pain or significant distress. A score of 3 or above is considered to be the threshold for initiating pain treatment. Pain will be assessed using the FLACC scale 15 min before the procedure and at the time of cannulation. The 15-minute baseline assessment was chosen to capture the child’s resting state prior to procedural preparation and to minimise anticipatory anxiety effects. A reduction of 1.5 points in the FLACC score was considered clinically meaningful based on previous paediatric pain studies and internal data.
Secondary endpoint measures
The secondary outcomes are differences in the following criteria between the two groups:
Children’s distress during the procedure, assessed using the PRIC (Procedural Restraint Intensity in Children) scale (online supplemental appendix 2). This tool is designed to evaluate the level of physical restraint applied during paediatric procedures, serving as an indirect indicator of the child’s distress.35 36 The tool is stratified into five levels reflecting both the intensity of force used and the child’s behavioural responses. A score of ≥3 indicates a high level of restraint and suggests inadequate pain or anxiety management, prompting the need for reassessment and adaptation of the analgesic strategy. The PRIC score will be assessed during skin disinfection and identification of the venous access site, and at the time of skin puncture.
Change in heart rate during the procedure. Changes in heart rate may reflect physiological responses to pain and stress during painful procedures, reflecting changes in sympathetic and parasympathetic nervous system activity in response to nociceptive stimuli. Heart rate will be recorded 15 min before the procedure and at the time of cannulation. The primary analysis will focus on the change in heart rate between baseline and cannulation. Heart rate variability serves as a physiological indicator of pain, reflecting changes in sympathetic and parasympathetic nervous system activity in response to nociceptive stimuli.
Number of attempts before obtaining venous access and failure rate. The effectiveness of the procedure will also be evaluated by the number of attempts before a successful PIVC is achieved. An attempt is defined as the moment when the needle punctures the skin. For ethical reasons, a maximum of three attempts will be allowed after which the procedure will be considered a failure, and care will be transferred to the anaesthesia team. Failure is defined as the inability to establish peripheral intravenous access, as defined above, and the need to involve the anaesthesia team.
Parental anxiety during the procedure, assessed using the STAI (State Trait Anxiety Inventory) questionnaire at the end of the procedure. The STAI is a self-administered questionnaire containing 40 items,37 divided into two subscales: one assessing state anxiety (AS), which reflects the current emotional state (STAI-S) making it possible to assess the patient’s nervousness and anxiety; the other assessing trait anxiety (AT), which reflects the general or baseline level of anxiety (STAI-T). Parental anxiety will be assessed as it may influence the child’s emotional response and pain perception during medical procedures.
The parents’ satisfaction about the use of PARO will be evaluated using a questionnaire given to the parents 15 min after the end of the procedure. This questionnaire consists of four items with a Likert-type response scale (online supplemental appendix 3)
The healthcare team’s satisfaction about the integration of PARO into routine clinical practice will be assessed using a different questionnaire (online supplemental appendix 4). This questionnaire will be distributed to all the nursing staff involved in the study on its completion and will be completed only once by each participant. Additionally, one or more feedback meetings will be organised with the healthcare team at the end of the study to discuss their experiences and opinions regarding the intervention.
The trial flow chart is represented in figure 1. The flow diagram of the study procedures and timing of the outcome assessments is shown in figure 2. Figure 3 represents a child’s interaction with PARO during PIVC in the emergency department.
Figure 2. Flow diagram of the study procedures and timing of outcome assessments. Standard techniques include MEOPA and EMLA cream and may also include distraction techniques such as play therapy or watching cartoons, depending on the child’s preference. EMLA, Eutectic Mixture of Local Anaesthetics; FLACC, Face, Legs, Activity, Cry, Consolability; MEOPA, equimolar nitrous oxide–oxygen mixture; PRIC, Procedural Restraint Intensity in Children; STAI, State Trait Anxiety Inventory.
Figure 3. Interaction of a child with the PARO robot during peripheral intravenous cannulation. FLACC, Face, Legs, Activity, Cry, Consolability; PRIC, Procedural Restraint Intensity in Children; STAI-AE, STAI, State Trait Anxiety Inventory-State Anxiety; STAI-AT, STAI-Trait Anxiety.
Statistical methods
Statistical analyses will be performed by a biostatistician from the DRCI at Nice University Hospital using SAS Enterprise Guide V.7.1 (SAS).
The statistical analysis will first present a descriptive analysis of the study population and their measured parameters with absolute and relative frequencies (and their 95% CIs) for the categorical variables, and evaluation of means and SDs, medians and IQR for the quantitative variables. Model assumptions will be checked before the analyses are performed. All the models estimators will be presented along with their 95% CIs. All randomised patients will be included in the intention-to-treat (ITT) analysis, each patient will be analysed as a part of the group to which he or she was assigned at randomisation. For the primary objective, a per-protocol analysis will be conducted as a planned sensitivity analysis, including only patients without major protocol deviations (allocation error, technical problem or missing primary endpoint). However, these results will not be substituted for those of the ITT analysis. Given the short follow-up period (emergency room visit), minimal missing data are expected, therefore, no replacement of missing data is planned.
The primary outcome, defined as the FLACC score evolution between 15 min before and the time of PIVC, will be compared between groups using analysis of covariance (ANCOVA). The dependent variable will be the FLACC score evolution and the variable of interest, the treatment group. The model will be adjusted on the stratification factors (age (<2 or ≥2 years) and centre (with or without emergency room)), baseline FLACC value and the treatment received (MEOPA or EMLA cream) as covariates (online supplemental appendix 5).
Statistical significance will be set at a two-sided alpha level of 0.05.
Secondary endpoint analyses
Children’s distress during disinfection will be compared between the two groups using a linear regression model, with PRIC as the dependent variable and group as the main explanatory variable, adjusted for age and treatment.
This analysis will be repeated by replacing the PRIC score during disinfection with the PRIC score at the time of skin puncture.
The analysis of heart rate evolution will be performed in the same manner as for the primary objective.
The comparison of the number of attempts will be carried out using a Poisson regression model, with the number of attempts (maximum 3) as the dependent variable and the treatment group as the main explanatory variable, adjusted for age and treatment.
Parental anxiety will be compared using a linear regression model, with the STAI-Y-A score (state anxiety) as the dependent variable and group as the main explanatory variable, adjusted for the STAI-Y-B score (trait anxiety), age and treatment.
The comparison of failure rates will be performed using a logistic regression model, with placement failure as the dependent variable and group as the main explanatory variable, adjusted for age and treatment.
Parental and paramedical satisfaction will be described using absolute and relative frequencies for each question.
Sample size
The primary outcome of this study will be pain intensity, assessed using the FLACC scale. Based on internal data from the Emergency Department of Nice Lenval University Hospital, we estimate that the mean increase in pain between baseline (15 min before the procedure) and the time of cannulation is 2.5 points (SD 4.35) in patients receiving standard pain management. We hypothesise that the mean increase in FLACC score will be 1 point in the PARO group, corresponding to a 1.5-point lower increase compared with standard pain management. Assuming a two-sided alpha level of 0.05, an ANCOVA model with two covariates, an R² of 0.6 for the covariates, a power of 80%, and a type I error rate of 5%, the required sample size is 108 patients (nQuery Advisor, V.7.0). To account for potential technical issues or missing data, an additional 10% of participants will be included, leading to a total sample size of 120 patients, 60 patients in each group. The expected effect size was based on internal data and was consistent with previously reported differences in procedural pain in paediatric populations.38 A 1.5-point reduction in FLACC score was considered clinically relevant by the investigators based on prior paediatric procedural pain literature.
Data management
All study data will be collected using a study-specific e-CRF (REDCap), designed by the DRCI Data Manager at Nice University Hospital under the responsibility of the principal investigator. Data quality will be ensured through monitoring visits, during which CRAs will verify adherence to the protocol, eligibility criteria, informed consent, and accuracy of recorded data. The Data Manager will perform validation and consistency checks, issuing queries when necessary. All database modifications will be logged. On study completion, the database will be locked and validated and signed by the principal investigator, the Data Manager and a DRCI statistician or methodologist. The locked database, together with the data management report, will then be provided to the study statistician for analysis. Access to study data will be controlled via role-specific permissions to ensure confidentiality and regulatory compliance. The full study protocol and statistical analysis plan will be available from the corresponding author on reasonable request. No independent data monitoring committee will be established as the study involves a low-risk, non-invasive intervention and a short follow-up period.
Patient and public involvement
Patients and the public were not involved in the design, conduct, reporting or dissemination plans of this research. Informal feedback from parents and healthcare professionals during preliminary clinical use of PARO informed the feasibility aspects of the protocol.
Discussion
This study will aim to evaluate the effectiveness of a socially assistive robot (PARO) as part of a multimodal approach to pain management during PIVC in children. If effective, this intervention could provide clinically relevant evidence supporting the integration of non-pharmacological strategies into routine paediatric care.
This study has several strengths, including its multicentre randomised design, the use of validated outcome measures, and its pragmatic approach reflecting real-life clinical practice. However, some limitations should be acknowledged. The open-label design may introduce observer bias, particularly given the behavioural nature of the primary outcome measure. In addition, variability in standard pain management practices across centres, including the use of different pharmacological approaches such as EMLA cream or MEOPA, may influence the results. Furthermore, the absence of a single standardised gold standard comparator may introduce heterogeneity in the control condition. Finally, the use of an observer-rated scale such as FLACC may introduce assessment bias, particularly in an open-label context. The visible presence of the PARO robot may also influence both child and caregiver behaviour, potentially contributing to a contextual or placebo effect.
Ethics and dissemination
Protocol amendments
Any amendments to the protocol will be submitted for approval to the relevant ethics committee and then updated to ClinicalTrials.gov trial registration. The trial is registered in ClinicalTrials.gov under the identifier No. NCT07299006.
Legal framework
This study has received advice and approval from the French National Agency for Medicines and Health Products Safety and the French Committee for the Protection of Personal Data (CPP Ouest I Tours on 3 July 2025, No.25.02471.000436). The study sponsor has purchased civil liability insurance. The trial is registered in the French trial database under the ID/RCB No. 2025-A00197-42.
The data processing is declared in the Nice University Hospital’s register of processing activities. The study will be conducted in accordance with the Declaration of Helsinki on ethical principles and obligations in biomedical research.
Consent or assent
Written informed consent will be obtained from one of the parents or the legal representative by the physician performing the randomisation or the CRA. Parents will be given a parent/legal representative information sheet. The patient and their parents will have the opportunity to ask questions and will be informed of their right to refuse to participate in the research or to withdraw from the trial at any time without giving any reason and without prejudice. The parents will be assured that their care will not be affected if they do not wish their child to participate. Verbal consent obtained from the participating child (if able to provide it) will be documented by nursing and medical staff. Refusal of consent will be recorded. Written informed consent for publication of the images in figures 2 and 3 was obtained from the participants’ legal guardians. The parent information sheet and consent form (online supplemental file 1) and the child information sheet (online supplemental file 2) are available as supplementary material.
Confidentiality
Personal information about potential and enrolled participants will be stored in a password-protected database. The password will be known by the research team only.
Dissemination policy
Results will be disseminated through publication in peer-reviewed journals and presentation at national and international conferences. Findings will also be communicated to healthcare professionals and relevant stakeholders, and a summary of results will be made available to participants on request. Data sharing will be considered in accordance with regulatory and institutional requirements. De-identified individual participant data, along with the data dictionary and statistical code, will be made available on reasonable request to the corresponding author, subject to approval by the sponsor and in accordance with applicable regulations.
Trial status
Recruitment started on 3 March 2026 and is expected to be completed on 30 March 2027.
Supplementary material
Footnotes
Funding: Additional funding was provided by Nice Lenval University Hospital in response to a call for projects, which enabled the funding of clinical research associates, the help of Nice University Hospital DRCI, and the insurance required for the study. Nice Lenval University Hospital, like PARO France, had no role in study design, data collection, analysis, interpretation or manuscript preparation.
Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2026-118505).
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Consent obtained from parent(s)/guardian(s).
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
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