Virtual reality (VR) has increasingly been explored in medical settings as a non-pharmacological intervention for the management of pain and anxiety associated with invasive procedures. By providing immersive and interactive environments, VR is thought to modulate both sensory and emotional components of pain through mechanisms involving focused attention, cognitive engagement, and altered perception, which share similarities with hypnosis-based approaches. Evidence from previous studies, initially conducted mainly in paediatric populations and more recently extended to adults, suggests that VR may effectively reduce procedural anxiety and pain without increasing procedural duration or clinical workload.

Oncology patients undergoing the placement of vascular access devices, such as peripherally inserted central catheters (PICC) and PICC-PORTs, frequently experience procedural distress, including anxiety and discomfort, related to the invasive nature of the intervention. Procedural anxiety may negatively influence patient experience, cooperation, and overall tolerance of the procedure, potentially increasing the need for pharmacological anxiolytic or analgesic support. Identifying effective, safe, and easily applicable non-pharmacological strategies to reduce distress during these procedures represents a relevant clinical goal in oncology care.

The present study aims to evaluate the effectiveness of virtual reality delivered via a head-mounted display in reducing patient-reported anxiety and pain in adult oncology patients undergoing PICC or PICC-PORT insertion.

This study is designed as a prospective, interventional, randomised controlled trial with a 1:1 allocation ratio using an independent, certified web-based randomisation service. Approximately 120 patients will be enrolled at a single centre, the Istituto Oncologico Veneto (IRCCS), and randomly assigned to one of two study arms. Participants allocated to the intervention arm will receive VR in addition to the standard of care (VR + SOC) throughout the vascular access placement procedure, while participants in the control arm will undergo the standard procedure alone (SOC).

The VR intervention will be delivered using HypnoVR, a software-based medical device classified as Class I, non-sterile, and compliant with Regulation (EU) 2017/745 on Medical Devices. The intervention will be administered via a head-mounted display with audiovisual content designed to promote relaxation, focused attention, and emotional regulation during the procedure.

The primary outcome of this study is a composite patient-reported procedural experience endpoint, assessed immediately after the procedure. The primary analytical component of this composite endpoint is procedural anxiety, measured using a 10-point Visual Analogue Scale for Anxiety (VAS-A). The main statistical analysis will compare changes in VAS-A scores between the intervention group and the control group.

The additional dimensions of the composite endpoint, patient-reported comfort, satisfaction and procedural tolerability, are collected concurrently and are not aggregated into a single score. These dimensions are analysed separately and interpreted jointly with procedural anxiety in order to provide an overall assessment of the patient's procedural experience.

Secondary outcomes include: 1) procedural pain, assessed using a 10-point Visual Analogue Scale (VAS); 2) physiological parameters, including heart rate and arterial blood pressure; 3) procedural characteristics, such as procedure duration and number of device insertion attempts; 4) qualitative assessment of patients' perceptions and lived experiences of the procedure, analysed using Van Kaam's phenomenological method18.

Data collection will include both quantitative and qualitative measures within a mixed-methods framework. Quantitative data will be analysed using descriptive and inferential statistical methods to assess differences between study groups, while qualitative data derived from semi-structured interviews will be analysed using the Van Kaam phenomenological method to explore patients' lived experiences. The aim of this study is to evaluate the effect of an immersive virtual reality intervention on the overall procedural experience of adult oncology patients undergoing PICC and PICC-PORT placement, with patient experience conceived as a primary dimension of quality of care.

BACKGROUND

In recent years, virtual reality (VR) has found increasingly widespread and innovative applications in the field of medicine, particularly within rehabilitation pathways, medical education, and the management of mental health conditions as well as chronic and acute pain. Numerous studies have demonstrated that the immersive experience created by VR restricts individuals' cognitive capacity to process acute pain and anxiety, and that this approach is more effective than simpler distraction-based methods.

The modulation of anxiety and pain through the use of VR is enabled by mechanisms associated with hypnosis, attentional shifting, and skills acquisition. Hypnosis aims to divert patients' attention away from painful and anxiety-provoking stimuli by immersing them in a virtual environment. The sensory and cognitive hypnotic mechanisms offered by VR lead to diversion of pain signals and interference with their processing at the level of the neuromatrix. Distraction represents a dispersion of attention towards multiple, uncontrolled stimuli, reducing voluntary attentional capacity; in contrast, hypnosis is characterised by a state of focused attention and heightened suggestibility, in which individuals remain conscious while intentionally directing their internal focus. Relaxing virtual environments are capable of modulating emotional responses, reducing both pain and anxiety, while active engagement enhances perceived control and further decreases pain perception. VR is able to influence brain activity by modulating neuromatrix responses to pain and by providing an integrated experience capable of acting across multiple dimensions.

Anxiety and pain are among the most frequently reported sensations before and during vascular access placement, in both paediatric and adult populations. However, the majority of existing literature focuses on the use of VR as a non-pharmacological distraction technique primarily in paediatric patients, largely neglecting its application in adult patients undergoing similar procedures.

The use of VR delivered through a head-mounted display during vascular access placement, specifically PICC and PICC-PORT insertion, in adult populations is only marginally reported in the literature. A prospective, multicentre, randomised controlled study demonstrated reductions in anxiety and pain among patients exposed to VR compared with standard care, without prolonging procedural time and with a reduction in the use of anaesthetic and analgesic agents. However, this study also highlighted that several factors influence patients' responses and the applicability of VR. Individual characteristics such as mood, personality, expectations, and previous experiences may affect responsiveness to VR. Nevertheless, VR represents a valid and promising non-pharmacological alternative for procedural sedation.

RESEARCH QUESTION Is the use of virtual reality delivered through a head-mounted display, worn by oncology patients during vascular access placement, specifically PICC and PICC-PORT, effective in improving the lived procedural experience in terms of anxiety, pain, confort and satisfaction compared with patients undergoing the standard device implantation procedure? PRIMARY OBJECTIVE The primary objective of the study is to evaluate the effectiveness of virtual reality delivered through a head-mounted display in oncology patients undergoing vascular access placement, specifically PICC and PICC-PORT insertion.

The secondary objectives are as follows:

To evaluate the effectiveness of immersive virtual reality (VR) delivered through a head-mounted display in reducing patient-reported procedural pain levels compared with standard care alone.

To evaluate the effect of VR on physiological parameters (heart rate and arterial blood pressure) during the procedure.

To evaluate the effect of VR on procedural characteristics, including procedure duration and number of insertion attempts.

To explore patients' lived experiences and perceptions of the procedure through qualitative analysis using Van Kaam's phenomenological method.

Primary Endpoint The primary endpoint is a composite patient-reported procedural experience endpoint, assessed immediately after the procedure (T1). The composite integrates multiple dimensions of procedural experience, with change in procedural anxiety (measured using a 10-point Visual Analogue Scale for Anxiety, VAS-A) serving as the prespecified principal quantitative driver. The remaining component dimensions, patient-reported comfort, satisfaction, and procedural tolerability, are analysed as individual, non-aggregated measures and interpreted jointly with anxiety. No numerical aggregation of component scores is applied.

Secondary Endpoints

Secondary endpoints include the following, assessed in the VR group relative to the control group:

Procedural pain, measured using a 10-point Visual Analogue Scale (VAS). Physiological parameters (heart rate, systolic, diastolic, and mean arterial pressure).

Procedural characteristics (procedure duration and number of insertion attempts).

Qualitative assessment of patients' perceptions and lived experiences related to the procedure, analysed using Van Kaam's phenomenological method.

STUDY DESIGN Prospective, interventional, randomised controlled study. The randomisation sequence is generated using an independent, certified web-based randomisation service with a 1:1 allocation ratio.

SAMPLE

Approximately a total of 120 patients will be enrolled and allocated to two treatment arms:

Arm A (60 patients): VR delivered via head-mounted display plus standard of care in oncology patients undergoing PICC or PICC-PORT insertion.

Arm B (60 patients): Standard care alone for oncology patients undergoing PICC or PICC-PORT placement.

INCLUSION CRITERIA Age ≥ 18 years Ability to understand the Italian language Oncological diagnosis Patients undergoing PICC or PICC-PORT insertion EXCLUSION CRITERIA Refusal to participate Inability to provide informed consent Visual or auditory impairments Sensory deficits affecting the procedural area Cognitive or psychiatric disorders that could compromise data reliability STUDY DURATION Start of recruitment: 01/07/2025 End of recruitment: 30/05/2026 Data analysis period: 01/06/2026 - 31/07/2026 End of study: 31/07/2026 Total study duration: 12 months STUDY CENTRE The study will be conducted at a single centre: Istituto Oncologico Veneto, within the facilities dedicated to vascular access placement in the Department of Oncological Surgery.

INTERVENTION Arm A: Virtual Reality + Standard of Care (VR + SOC) Patients will receive standard care for PICC or PICC-PORT placement, combined with VR delivered via a head-mounted display throughout the procedure.

The VR system used is HypnoVR, developed by Medival s.r.l. It is a Class I non-sterile software-based medical device compliant with Regulation (EU) 2017/745 on Medical Devices. Accessories compliant with Directive 2014/53/EU include a VR headset, Lenovo tablet, and Bluetooth headphones. The full system is contained in a dedicated transport case. HypnoVR has been marketed in Italy since 2023 and does not contain latex or phthalates.

HypnoVR integrates clinical hypnosis with immersive virtual environments, guided breathing, music therapy-based compositions, and cardiac coherence techniques, providing multisensory therapeutic immersion. Continuous communication with patients will be maintained throughout the session, and patients may select preferred visual and musical environments. HypnoVR can be used in individuals aged seven years and above and is applied across multiple clinical settings, including oncology procedures and vascular access placement.

Arm B: Standard of Care (SOC) Patients will undergo standard care for PICC or PICC-PORT placement without VR. Sample size calculation The sample size calculation was based on procedural anxiety (VAS-A, 0-10), which serves as the principal quantitative driver of the composite primary outcome. Based on literature evidence and clinical considerations, a minimal clinically relevant difference of 1.5 points on the 10-point VAS-A was assumed, with an expected standard deviation of 2.5 (Cohen's d = 0.6). A two-sided significance level of 0.05 and a statistical power of 90% were applied. Using the standard formula for comparison of independent means, a sample size of 59 participants per group (118 total) was obtained. Accounting for an anticipated dropout rate of 10%, the final target sample size was set at 120 participants.

DATA COLLECTION Data collection will follow a mixed-methods research design, incorporating both quantitative and qualitative variables. Data will be collected at two time points: before device placement (T0) and after placement (T1).

DATA ANALYSIS Quantitative data will be analysed using descriptive statistics, regression models, and tests of independence to assess associations between independent and outcome variables. Qualitative data derived from semi-structured interviews will be analysed using the Van Kaam method.

Inclusion Criteria

• Adults aged 18 years or older
• Diagnosis of neoplastic disease (solid or haematological malignancy)
• Patients scheduled for peripherally inserted central catheter (PICC) or PICC-PORT placement
• Ability to understand the Italian language
• Ability and willingness to provide written informed consent

Exclusion Criteria

• Refusal to participate in the study
• Inability to provide informed consent
• Visual or auditory impairments that may interfere with the use of a virtual reality head-mounted display
• Sensory deficits involving the anatomical area affected by the procedure
• Cognitive, neurological, or psychiatric disorders that may compromise comprehension, cooperation, or reliability of patient-reported outcomes
• Any condition judged by the investigator to make participation unsafe or inappropriate

Individual participant data collected during this study will not be shared publicly. Only aggregated and anonymised data will be reported in scientific publications and presentations. Any data sharing beyond these outputs would require additional ethical approval and amendments to the informed consent.