A Prospective Randomized Controlled Monocentric Study Evaluating the Impact of Virtual Reality Hypnosis During Labor
Phase: NA
Conditions: Labor Pain, Virtual Reality, Hypnosis
Sponsor: Clinique Saint-Jean, Bruxelles

VRH4L, Protocol, Version 2 dated 23/02/2021 
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A prospective randomized controlled monocentric study evaluating the impact of  
Virtual Reality Hypnosis during labor  
 
VRH4L  
 
 
 
Principal Investigator: 
Bosteels Arnaud MD 
Department of anesthesia 
Clinique Saint-Jean Bruxelles (SJ) 
32, Boulevard du jardin botanique, 
1000 Bruxelles 
 
Principal Co-Investigators: 
Piccart Louise MD 
Schaub Isabelle MD 
Clinique Saint-Jean Bruxelles (SJ) 
 
 
Sponsor: 
Department of Anesthesia, Clinique Saint-Jean Bruxelles (SJ) 
Boulevard du jardin Botanique 32 
1000 Bruxelles 
 
 
Protocol version: 2 
Release date: 23/02/ 2021 
 
 
 
 
 
 
 
 
 
 
 
 

VRH4L, Protocol, Version 2 dated 23/02/2021 
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1. 
PROTOCOL APPROVAL- Signature Page .................................................................... 3 
2. 
DOCUMENT HISTORY .................................................................................................... 3 
3. 
SYNOPSIS ....................................................................................................................... 4 
4. 
RATIONALE ..................................................................................................................... 6 
4.1. CONTEXT AND JUSTIFICATION OF THE STUDY ...................................................... 6 
4.1.1. Standard of care ......................................................................................................... 6 
4.1.2. Alternatives to standard of care .................................................................................. 6 
4.1.3. Hypothesis .................................................................................................................. 7 
5. 
STUDY OBJECTIVES ...................................................................................................... 7 
5.1 PRIMARY OUTCOME .................................................................................................... 7 
5.2 SECONDARY OUTCOMES ........................................................................................... 7 
6. 
STUDY DESIGN ............................................................................................................... 7 
7. 
STUDY POPULATION ..................................................................................................... 8 
7.1. INCLUSION CRITERIA ................................................................................................. 8 
7.2. EXCLUSION CRITERIA ................................................................................................ 8 
7.3. INCLUSION CRITERIA FOR INVESTIGATORS .......................................................... 8 
8. 
CONCOMITTANT MEDICATION AND TREATMENT ..................................................... 8 
9. 
SCHEDULE OF ASSESMENTS AND PROCEDURES ................................................... 9 
10. 
SELECTION AND WITHDRAWAL OF SUBJECTS .................................................. 10 
11. 
STATISTICAL CONSIDERATIONS AND ANALYTIC PLAN .................................... 10 
11.1 SAMPLE SIZE ............................................................................................................ 10 
11.2 SEQUENCE GENERERATION .................................................................................. 10 
11.3 CONCEALMENT MECHANISM AND IMPLEMENTATION ....................................... 10 
11.4 ANALYSIS .................................................................................................................. 11 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE ................................................ 11 
13. 
ETHICAL ASPECTS .................................................................................................. 11 
13.1 HARMS ....................................................................................................................... 11 
13.2 RESEARCH ETHICS APPROVALS ........................................................................... 12 
13.3 CONSENT OR ASSENT ............................................................................................ 12 
13.4 CONFIDENTIALITY AND ACCESS TO DATA ........................................................... 12 
13.4 DECLARATION OF INTERESTS ............................................................................... 12 
14. 
DATA HANDLING AND RECORD KEEPING ........................................................... 13 
14.1 DATA COLLECTION METHODS AND RETENTION ................................................. 13 
14.2 DATA MANAGEMENT ............................................................................................... 13 
15. 
PUBLICATION POLICY ............................................................................................. 13 
15.1 TRIAL RESULTS AN REPRODUCIBLE RESEARCH ............................................... 13 
15.2 AUTHORSHIP ............................................................................................................ 13 
16. 
FINANCE AND INSURANCE ..................................................................................... 13 
16.1 SPONSOR .................................................................................................................. 13 
16.2 INSURANCE .............................................................................................................. 13 
17. 
ABBREVIATIONS ...................................................................................................... 14 
18.REFERENCES .................................................................................................................. 15 
 
 
 

VRH4L, Protocol, Version 2 dated 23/02/2021 
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1. PROTOCOL APPROVAL- Signature Page 
 
The signature below constitutes the approval of this protocol and the attachments, and provides the 
necessary assurances that this trial will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and regulatory 
requirements and applicable European regulations and ICH guidelines. 
 
 
 
Study coordinators/Principal investigators 
 
Name and Title 
Approval date 
Signature 
Dr Bosteels Arnaud (AB) 
06/08/2020 
 
Dr Piccart Louise (LP) 
06/08/2020 
 
Dr Schaub Isabelle (IS) 
06/08/2020 
 
Ms Peeters Fleur (FP) 
06/08/2020 
 
 
Sponsor 
Name and Title 
Approval date 
Signature 
Department 
of 
Anesthesia, 
Clinique Saint-Jean Bruxelles 
(SJ)  
06/08/2020 
 
 
 
2. DOCUMENT HISTORY 
 
Version 
Protocol version 
issue date 
Short description of modifications 
1 
04/08/2020 
Original Protocol (Version 1) 
2 
23/02/2021 
Adapted protocol (Version 2) 
 
 
 
 
 

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3. SYNOPSIS 
 
STUDY TITLE 
A randomized controlled, single centre, study evaluating the impact of Virtual Reality 
Hypnosis during labor 
SHORT TITLE 
VRH4L (Hypnotic Virtual Reality for Labor pain relief) 
PROTOCOL 
NUMBER 
2 
SPONSOR 
Department of Anesthesia, Clinique Saint-Jean Bruxelles (SJ) 
STUDY 
POPULATION 
Women during labor 
 
PHASE 
Prospective interventional Randomized Controlled Trial (RCT) 
STUDY  
DESIGN 
This prospective interventional RCT will evaluate efficacy of Virtual Reality Hypnosis 
(VRH) in reducing pain during labor. Hypnosis is delivered as a standardized 
therapeutic intervention through virtual reality, using a digital sedation software. This 
VRH module is called AQUA© (Oncomfort SA) and is specifically designed  for the 
management of pain and anxiety during labor. 
 
Women who are planning to give birth at the St-Jean Hospital are recruited at prenatal 
consultation some weeks before the calculated delivery date. Only patients with a 
planned induced labor can be included.Patients who agree to participate sign an 
informed consent form. 
38 patients will be randomized in two arms (19 patients in each cohort): 
• 
Patients in the intervention groups will receive a session of the  AQUA© Digital 
Sedation module when in active labor (cervical dilatation ≥4 cm, contractions 
every 5 minutes, NRS pain score ≥4/10) on top of the standard of care 
• 
Patients in the control group will receive standard of care only. 
 
Patients are allowed to discontinue the VRH session at any time. A study staff member 
is present during the session to explain the intervention and fill in the questionnaires. 
Furthermore, she/he ensures the patient is receiving appropriate clinical care 
throughout the duration of the intervention. 
Information from patient’s report will be collected before the intervention, after the 
intervention and up to the patient’s discharge from the maternity on day after childbirth. 
A log will be kept of patients who refuse to participate in the study.  
 
OBJECTIVES 
AND 
ENDPOINTS 
Primary objective 
Primary endpoints 
To evaluate efficacy of VRH  
AQUA© module on labor-related 
pain  
Difference in NRS (Numerial Rating Scale 0 to 10) 
pain scores before and after the intervention  
Secondary objectives 
Secondary endpoints 
To compare patient experience in 
both arms 
Measure of NRS pain after 30 minutes 
Measure of satisfaction by Likert Scale (0 to 5) 
Measure of nausea by Nausea and Vomiting 
Score (0 to 3) 
Evaluation of comfort during intervention with the 
CPOT scale (Critical care Patient Observation 
Tool 0 to 8) and heart rate 
Willingness to undergo a potential next labor with 
VRH 
Willingness to recommend VRH to acquaintances 
 
To assess selected safety and 
efficacy outcomes in both arms 
Progression of labor 
Need for epidural 

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Need for medication: type and dosages during 
stay 
Frequency and type of (severe) adverse events 
(SAEs) (mother and baby) 
If the patient removes the headset during the 
session, motivation is documented. 
To 
assess 
gynecologist 
and 
nurse satisfaction   
Measure of satisfaction of the midwife and 
obstetrician by the Likert scale (0 to 5)  
Quality of the therapeutic relationship between the 
midwife and patient (reported by the midwife in a 
NRS from 0 to 10) 
Evaluation of vital signs 
Oxygen saturation 
Systolic and diastolic blood pressure 
Heart rate (during and in between contractions) 
NUMBERS OF 
PARTICIPANTS 
38 
INCLUSION 
CRITERIA 
1. Age: ≥ 18 and ≤ 45 years 
2. Pregnant with term gestation 
3. Willing to adhere to the rules linked to the use of the VRH headset: turning off mobile 
phone, visit bathroom in advance, no new visitors and no interference of the partner 
other than when the woman would ask him so 
4. Provision of written informed consent  
5. Induced labor 
EXCLUSION 
CRITERIA 
1. Complicated pregnancy ( HELLP,…) 
2. Scheduled caesarian delivery 
3. Receipt of epidural analgesia or opioid painkillers before start active labor phase 
4. Low auditory acuity that precludes use of the device 
5. Low visual acuity that precludes use of the device 
6. Head or face wounds precluding use of the device 
7. Schizophrenia 
8. Epilepsy 
9. Dizziness 
10. Non-proficiency in French and/or Dutch (research language) 
 
MEDICAL 
DEVICE 
The Digital Sedation session used is the AQUA© (module 3.2) delivered through the 
Sedakit™, both developed by Oncomfort®. 
 
According to Annex IX of Directive 93/42 / EEC, the SedakitTM is classified as a Class I 
Medical Device, it is a non-invasive device that is in contact only with the skin. 
The Sedakit™ consists of an audio headset, virtual reality goggles, a mobile phone,  
AQUA© software and the user’s manual. 
 
Digital Sedation allows an immersive experience of virtual reality focused on the 
induction of relaxation. As a solution for non-pharmacological sedation and self-
management of pain and anxiety, AQUA© takes the subject into a deep sensory 
experience and allows her to dive into a soothing environment. The subject will be 
required to perform simple stress management exercises; helping her to better manage 
her pain and anxiety. 
The techniques used is a virtual reality headset combined with an audio recording of 
psychological interventions, mainly clinical hypnosis.  
STATISTICAL 
ASPECTS 
Inclusion of 38 patients is necessary to ensure statistical significance. Participants are 
randomized and the investigators are not blinded. 
STUDY 
MILESTONES  
First patient, first visit: March 1, 2021 
Last patient, last visit: May 30, 2021 

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4. RATIONALE  
4.1.CONTEXT AND JUSTIFICATION OF THE STUDY 
Labor pain is feared by many women. However some women recall positive feelings about their 
coping ability with this intense pain. The way they dealt with pain seems more important than the 
severity of the labor pain. The feeling of being in control, respected and nurtured by caregivers and 
loved ones is what these women recall mostly.i 
On the other hand, many women recall feelings of suffering, loneliness and helplessness. These 
negative feelings make the whole childbirth experience unpleasant. Even a posttraumatic stress 
disorder can develop after childbirth. The ability to cope with this pain is influenced by experiences that 
took place before childbirth. It is probably more likely to have dysfunctional coping skills when earlier 
traumas were never resolved.i We believe that Virtual Reality Hypnois (VRH) can improve the way 
women cope with pain during labor. Through self-hypnosis, the focus is moved from pain to positive 
feelings, thereby women feel less tensed and have a greater sense of self-control.  
 
Secondly women are increasingly striving for a more natural birth, minimizing medical interventions 
such as cervical examination, pharmacological analgesia, etc. As such they are looking for 
nonpharmacological approaches to decrease labor pain. 
There are different nonpharmacological (see section 4.1.2 alternatives for standard of care) 
techniques that can reduce side-effects, increase rates of breast feeding, and eventually increase 
satisfaction.ii,iii   
Immersive virtual reality (VR) has been shown to decrease pain in a non-pharmacological way and in 
a number of different situations.iv,v Studies are positive about the use of immersive VR therapy as 
analgesia during experimental pain in healthy subjects, changing dressings of burn patients and as an 
analgesic adjunct during physiotherapy.vi vii viii  
 
The pain accompanied with childbirth is nor acute nor chronic and thereby a complex unique 
experience for every woman. Some studies suggest that VR can help controlling the pain during the 
active stage of labor.  Outcomes like anxiety, use of pharmacological analgesia and satisfaction have 
also been studied.ix,x,xi  
  
Could the association of hypnosis with immersive VR have additive positive effects? Based on our 
internal experience, the use of Virtual Reality Hypnose (VRH) can increase the comfort for women in 
labor. We decided therefore to organize a trial to measure the benefits and side effects of this new 
technique. VRH has never been studied before as an analgesic for labor pain. 
 
The hypnotic virtual reality environments are designed by Oncomfort SA, a Belgian company who’s 
solution has already been extensively researched and published.xii The VRH session is a module 
called AQUA©, a relaxing experience based on clinical hypnosis, respiratory techniques and 
autogenic muscle relaxation. This hypnotic script will bring the patient in a state of auto-hypnosis. The 
Head Mounted Display (HMD) is a VR Gear from Samsung-Oculus and the mobile phone used is a 
Samsung Galaxy S7. 
 
4.1.1.Standard of care  
The standard treatment (ST) for labor pain as used in our hospital contains massage, aquatherapy 
and postural exercises. This is always available for any woman in labor. The VR group receives digital 
sedation and when asked the ST. In comparison to the control group who receives only the ST when 
asked.  
If ST is not sufficient, a patient can receive a pharmacological treatment or an epidural analgesia. 
However, in this study we will examine the efficacy of VRH before the use of epidural analgesia or 
pharmacological treatment.  
 
4.1.2.Alternatives to standard of care 
Audio-analgesia, aromatherapy, biofeedback, acupressure, TENS (Transcutaneous Electric 
Neurologic Stimulation) and massage are popular methods but are not proven to have a significant 
effect on labor pain. These are not available in our institution. On the other hand hydrotherapy, 
acupuncture and hypnosis have a proven significance as a tool for pain management during labor.xiii 
More specifically hypnosis may reduce the overall use of analgesia during labor. xiv 

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4.1.3.Hypothesis 
Our primary goal is to evaluate the analgesic benefits of Virtual Reality Hypnosis (VRH) compared to 
the standard of care (ST) solely.  
 
 
5. STUDY OBJECTIVES 
5.1 PRIMARY OUTCOME 
The primary endpoint is to compare the differences in NRS pain measured before and after the 
intervention during labor. (T3 minus T1) The Pain Numerical rating Scale (NRS) is a scale from 0 to 10 
well known by the medical staff. xv xvi 
5.2 SECONDARY OUTCOMES 
30 min after the end of the intervention the NRS pain is assessed once more. (T4) 
During the intervention the comfort of the patient is evaluated. (T2) To do this we use the CPOT 
(Critical care Pain Observation Tool). CPOT is a comfort scale for (non)-ventilated patients in the 
intensive care unit. We decided to use this score, because during the VR experience we cannot 
communicate with the patient, which is similar as in sedated patients. And in our own experience we 
see that the parameters that we look at to evaluate the comfort of the patient during a VR sedation are 
very similar to this scale. (Facial expression, body movements, muscle tension and vocalization 
together make a score of 0 to 8)xvii Vital signs like heart rate and blood pressure are parameters that 
are easily measured during the intervention and considered as objective for evaluating pain during 
labor. (T1,2,3,4) xviii 
Nausea is also actively evaluated. Thereforewe use the PONV rating scale from 0 to 3. (T1, T3, T4) 
Anxiety is evaluated with the NRS at the same time. (T1, T2, T3) We use the Likert satisfaction scale 
(from 0 to 5) to explore the satisfaction directly after their experience and the day after delivery. (T3, 
T6) 
Willingness to repeat the intervention and to recommend the intervention can correlate with 
satisfaction of the overall experience. (T6) 
Progression of labor is followed with the degree of the cervix dilatation, therefore we will not perform 
more cervical examinations than needed but interpret the measurement of the midwives/obstetricians. 
(T5) 
 
The midwives are asked to evaluate the therapeutic link between themselves and the patient (NRS) 
after the women return to the maternity ward. (T5)  
All the medication received during the stay on the delivery ward, adverse events and interruptions from 
the intervention is noted. (T3, T5) 
 
6. STUDY DESIGN 
The VRH4L trial is an interventional, randomized, controlled, single-center, parallel group trial. 
Randomization will be done as a block randomization with a 1:1 allocationxix 
Clinique Saint-Jean Brussels (SJ), where the study takes place, is an academic hospital in the 
center of Brussels with around  than 2000 deliveries per year. 
We create two groups: the VRH group and the control group. During the intervention (T1-3) the VRH-
group receives a digital sedation in contrary to the control group who will not use the VRH headset.  
  
 
 
 
 
 

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7. STUDY POPULATION 
7.1. INCLUSION CRITERIA 
Patients must meet all of the following criteria in order to be eligible for this study: 
1. Age: ≥ 18 and ≤ 45 years 
2. Pregnant with term gestation 
3. Willing to adhere to the rules linked to the use of the VRH headset: turning off mobile phone, visit 
bathroom in advance, no new visitors and no interference of the partner other than when the woman 
would ask him so. 
4. Provision of written informed consent  
5. Induced labor 
 
7.2.EXCLUSION CRITERIA 
Patients meeting any ONE of the following criteria are not eligible for this study: 
1. Complicated pregnancy (HELLP,… 
2. Scheduled caesarian delivery 
3. Receipt of epidural analgesia or opioid painkillers before start active labor phase 
4. Low auditory acuity that precludes use of the device 
5. Low visual acuity that precludes use of the device 
6. Head or face wounds precluding use of the device 
7. Schizophrenia8. Epilepsy 
9. Dizziness 
10. Non-proficiency in French and/or Dutch (research language) 
 
 
7.3.INCLUSION CRITERIA FOR INVESTIGATORS 
Every investigator will have to obtain the Oncomfort Academy certificatexx and a certificate of Good 
Clinical Pratice (GCP)xxi.  
 
8. CONCOMITTANT MEDICATION AND TREATMENT 
The standard labor pain management contains massage, aqua therapy and postural exercises. In our 
institution, opioid patient controlled intravenous infusion (Remifentanil) or N2O inhalation as analgesia 
in the first stages of active labor is not standard of care. Every women can ask for and receive (if no 
contra-indications) an epidural. In this study, however, we will only include patients without an 
epidural. After childbirth we use paracetamol and anti-inflammatory drugs as first line painkillers. When 
necessary opioids can be added.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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9. SCHEDULE OF ASSESMENTS AND PROCEDURES 
 
RCT T 
TO 
T1 
T2 
T3 
T4 
T5 
T6 
Delivery Phase 
Prenat 
consult 
Active Labor 
(study 
threshold) 
Day 0 
Labor 
Labor 
Labor 
End 
of 
Delive
ry 
Day 
1 
  
  
Before 
the 
Start AQUA 
During 
AQUA 
End 
AQUA 
T3+30 
min 
  
  
Screening/ ICF 
X 
  
  
  
  
  
  
Refusal questionnaire 
X 
  
  
  
  
  
  
Patient 
Quastionaires 
& 
Observation 
  
  
  
  
  
  
  
NRS pain 
  
X 
  
X 
X 
  
  
Nausea 
  
X 
  
X 
X 
  
  
Likert satisfaction  
  
  
  
 
  
  
X 
CPOT (VR comfort scale) 
  
  
X 
  
  
  
  
Willingness 
to 
repeat 
(intervention) 
  
  
  
  
  
  
X 
Recommend (intervention) 
  
  
  
  
  
  
X 
Practitioner questionnaire 
  
  
  
  
  
  
  
Monitored contractions (on 
the CTG during intervention) 
  
  
  
X 
  
  
  
Satisfaction midwife 
  
  
  
  
  
X 
  
Quality of the therapeutic 
relationship 
  
  
  
  
  
X 
  
Objective criteria 
  
  
  
  
  
  
  
Vital signs (Saturation) 
  
X 
X 
X 
X 
  
  
Medication received 
  
  
  
  
  
 
 X 
Epidural  
 
 
 
X 
X 
 
 
Progression of labor 
  
  
  
  
  
X 
  
(Serious) adverse events 
  
 X 
 X 
 X 
 X 
X 
  
Stop 
of 
digital 
sedation 
session 
  
  
  
X 
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 

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10. SELECTION AND WITHDRAWAL OF SUBJECTS 
During the prenatal visit (PNV = T0; some weeks before the due date) the pregnant women receive 
information about the the study and the use of VRH from the midwife. Each patient will be asked for 
participation in the study, after verifying the presence of the inclusion criteria and absence of any 
exclusion criteria. The registration checklist is filled in (questionnaire 1). If patients refuse, their 
motivation will be noted on the refusal questionnaire(questionnaire 4). All the included patients receive 
sufficient information and time to decide if they want to participte or not. After signing the informed 
consent (Questionnaire 2 resp) they will be immediatly randomized using block randomization (with  
excel). This will assign the pregnant woman to either control group or the VRH group. 
 
On the day of delivery every included patient will receive standard of care. When the women selected 
in the VR group are in active labor (NRS pain ≥ 4, cervical dilatation ≥4 cm and regular contractions 
(every five minutes) we present the VRH treatment (T1).  
Patients who refuse the VRH treatment (T1) or remove the VRH headset during(T2) will be asked to fill 
in questionnaire 4 (refusal questionnaire). They will be considered as drop outs.  
 
11. STATISTICAL CONSIDERATIONS AND ANALYTIC PLAN 
11.1 SAMPLE SIZE 
The sample size of the study is computed on the basis of expectations for the the difference of the 
pain NRS means between the two arms at final analysis. Based on previous studies (Yildrim 2004 and 
Harmon 1990), we may expect a difference of the pain NRS means of 2 or more between the two 
arms, with a standard deviation of the pain NRS of 2 in both arms. For a statistical power of 80%, an 
alpha error of 5% and a two-sided test, 17 evaluable patients are needed in each group to reach 
statistical significance (calculation performed with Stata/MP 14.1).  
Assuming a potential drop out rate of 10% in each arm, a total of 19 patients need to be randomized to 
each arm. The total number of patients for the study is 38. 
11.2 SEQUENCE GENERERATION 
We created a block randomization in excel. This block randomization, has variable block sizes to 
decrease the chance of deducing the following allocation. The patients will be randomly allocated in 
either the either the control group or the VRH group in a 1:1 allocation.   
11.3 CONCEALMENT MECHANISM AND IMPLEMENTATION 
On the prenatal visit an investigator randomizes incuded patients (after they signed the IC) and gives 
them a study number as described in section ‘13.4 confidentiality and access to data’. A pop up in their 
electronic file and all the 4 questionnaires are kept together in one plastic sheet (one folder with 4 
questionnaires per patient: registration checklist, informed consent, data collection form and refusal 
questionnaire) in a closet of the prenatal visit. Every day all folders of incuded patients are moved from 
the prenatal visit to the maternity ward (by the study nurse) where there is also a predetermined 
closed closet to store all the forms. 
 
When the patient arrives on the labor ward to give birth (due day) the midwifes are aware of their 
participation in the study thanks to the pop up in their electronic file. On this day, we explain again the 
study to the patient and give them the possibility to drop out. The reason why is always noted on 
Questionnaire 4 (refusal questionnaire).  
 
The investigators (AB, LP, IS , FP) will not be blinded to the allocation because they can see if patients 
have the VRH experience or not during measurements.  
 
 
 
 

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11.4 ANALYSIS 
First descriptive analysis will be performed. Qualitative data will be described by frequency and 
percentage. Quantitative data will be described by mean, standard deviation, median, minimum, and 
maximum numbers.  
Regarding the primary outcome, NRS pain score before and after the intervention will be compared 
using paired t-test or Mann-Whitney test, depending of data distribution. 95% confidence intervals will 
be provided. 
Regarding secondary outcomes, chi-squared tests will be used to compare frequencies and rates 
between groups. In case of small cell sizes, we will alternatively use the Fisher’s exact test. T-Test or 
Mann-Whitney test will be used to determine if there is a significant difference between means of the 
two groups. T-Test or Mann-Whitney test will be also used for all continuous data normally distributed 
or not such as NRS, Likert scale and physiologic data. Repeated measurements such as Anxiety and 
Nausea will be handled with appropriate techniques such as paired tests. 
Safety variables include the incidence of Serious Adverse Events (SAEs), discomfort and the quality of 
immediate and distant labor pain analgesia. These data will be tabulated by treatment groups and 
overall, in contingency table for percentages or in descriptive univariate analyzes for continuous 
variables.  
  
The Intent-to-Treat (ITT) population will be used for all efficacy and safety analyzes unless otherwise 
specified. This ITT analysis will include all randomized patients, according to their allocation group.  
The Per-Protocol (PP) population will be used to validate the effectiveness of the studied intervention, 
as specified by the primary outcome. This PP analysis will include all patients in the ITT population 
who do not have a major violation of the protocol. The list of major violations includes at least:  
• Non-administered medication  
• Failure to meet an inclusion or exclusion criterion  
Patients identified as having major violations will be screened to determine their final exclusion from 
the PP population, prior to the freezing of the database. 
 
  
12. QUALITY CONTROL AND QUALITY ASSURANCE 
Increased adherence to the protocol is acquired by multiple information sessions about the study for 
the midwives. Furthermore, a reminder poster will be displayed in their office. Adherence to the 
protocol by the participants will be monitored daily by a non-blinded investigator (LP) by looking at the 
daily reports of the study. 
 
Patients will be well informed in advance about the study and the intervention on the prenatal visit. 
The informed consent must be signed to be included.  
 
We refer to the section data handling to remind that we have attention for the privacy of the patient 
and their data. They will remain anonym participants.  
 
Furthermore, we use standard forms with standard questions who are the same for every patient. 
(Questionnaire 1-4) Suggestive questions and subjective evaluations are not accepted. Also, the 
standard of care is a standardized protocol for every woman in active labor.  
 
Important protocol modifications wille be communicated to relevant parties. See appendix ‘Clinical 
study agreement’ Article 3 ‘Clinical study – Changes or modifications’.  
 
 
13. ETHICAL ASPECTS 
13.1 HARMS 
On every form used to collect data there is a possibility to report important information concerning 
possible harms during the study. This information will be analyzed and discussed by the investigators 
and reported in the study.  See appendix ‘Clinical study agreement’ Article 3 ‘Clinical study-Safety 
reports’.  

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13.2 RESEARCH ETHICS APPROVALS 
The central ethical committee (EC) is the Comité d’éthique Hospitalo-facultaire Saint-Luc-UCLouvain. 
They will evaluate the research proposition, check the scientific relevance and make sure the patient’s 
rights are respected. Approval granted on February 23, 2021 (study number: 2020/11AOU/403, Eudra-
CT nr: 2020-003935-95) 
  
The EC of Saint-Jean (OM 072) will check if the local investigator is able to and if the local conditions 
are met to participate in this study accord according to the law of May the 7th  2004. Approval granted 
on ### 
13.3 CONSENT OR ASSENT 
Every investigator will be taking part in the recruitment of the patients.  
Each includable patient will be approached on the prenatal visit and asked for participation in the 
study, after verifying the inclusion criteria and the absence of the exclusion criteria.  
The investigators will present the study to the patients, using a patient oriented explicatory form, after 
which they will look at the informed consent together with the patient. 
They will receive the following information: 
- 
The aim of this research 
- 
The duration of their participation in this research 
- 
Their participatrion has to be based solelyon their own free choice 
- 
Profits that may result from the research 
- 
Demonstrates how medical care will be continued at the end of the research, in case of 
premature termination of the research and in case of exclusion from the research, where 
applicable 
- 
Confidentiality of data and the possibility to withdraw from the research at any time. 
 
 
If necessary they will give the patient some time to reflect and come back to sign and collect, or not, 
the informed consent. After signing by the patient and the investigating physician, a copy of this 
document will be given to the individual research participant. The investigator must keep a second 
copy of the signed inormed consent in the archives for a minimum of 15 years. 
See appendix  17.1 ‘Informed consent’.  
 
13.4 CONFIDENTIALITY AND ACCESS TO DATA 
Every patient gets a code to anonymize her. The code will be a tree number code following VRH4L 
(VRH4L XXX) Information leading to their identity will be kept in the protected database file.  
This database is only accessible to the lead investigators. (requiring a password) 
The IC forms and data forms will be kept in a closet with very limited access.  
See appendix ‘Clinical study agreement’ Article 9 ‘Data privacy’ and Article 5 ‘Confidentialy’. 
13.4 DECLARATION OF INTERESTS 
There is no potential conflict of interest for any investigator. The Principal investigator (AB) is member 
of the clinical advisory board of Oncomfort SA. There is only a financial compensation for expences 
related to participacion of scientific meetings. 
 
 
 
 
 
 
 
 
 
 
 
 

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14. DATA HANDLING AND RECORD KEEPING 
14.1 DATA COLLECTION METHODS AND RETENTION 
There are four paper forms per patient that are used to collect the data that we put together in one 
plastic sheet (folder). Questionnaire 1 is the registration checklist where inclusion and exclusion 
criteria are checked, the study number and randomization group is noted. Questionnaire 2 is the 
informed consent signed by the patient and the investigator. Questionnaire 3 is the data collection 
form used by the investigators to note all the outcomes previously described. Questionnaire 4 is a 
refusal questionnaire where all reasons of refusal or interruption of the VRH can be assessed 
standardized. 
 
The investigators earned the Oncomfort Academy certificate and a Good Clinical Practice certificate.  
Midwives on the ward have already a year of experience with the VRH therapy for labor pain.  
 
 
14.2 DATA MANAGEMENT 
The investigators are responsible for the forms and for the database. They will collect all the forms on 
the first working day after the delivery (Day after delivery = D+1). They will put all the data 
anonymously in a protected database after every investigator verifies the entry of the data previously 
collected by him. 
 
 
 
15. PUBLICATION POLICY 
15.1 TRIAL RESULTS AN REPRODUCIBLE RESEARCH 
The investigators are intended to publish the results, even if not significant, so other investigators can 
be aware of this study.  
Information about publication of the results are mentioned in appendix ‘Clinical study agreement’ 
Article 11 ‘publication’.  
15.2 AUTHORSHIP 
Every investigator will be named as an author if he meets the criteria for authorship defined by the 
International Committee of Medical Journal Committee of Medical Journal Editorsxxii.   
 
 
16. FINANCE AND INSURANCE 
16.1 SPONSOR 
The primary sponsor is the Department of Anesthesia, Clinique Saint-Jean (SJ).  
Oncomfort SA provides the headsets that are needed to perform the study. 
16.2 INSURANCE 
The primary sponsor, the department of Anaesthesia, Clinique Saint-Jean,  provides an adapted 
contract. 
 
 
 
 
 
 
 

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17. ABBREVIATIONS  
DiS: Digital Sedation 
DD: Delivery Day 
HMD: Head Mounted Display (headset) 
IASP: International Association for the Study of Pain  
PNV: Prenatal Visit 
D+1: Post-Partum Day 1  
SJ: Clinique Saint-Jean Brussels 
ST: Standard Treatment 
NRS: Numerical Rating Scale 
VR: Virtual Reality 
VRH: Virtual Reality Hypnosis 
WHO: World Health Organisation 
TAP: Transversus Abdominal Plane Block 
PP: Per-Protocol (patient population) 
EC: Ethical committee 
VRCAS: VR comfort assessment scale 
GCP: Good Clinical Practice 
IC: Informed Consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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