Does the Application of Cold Decreases the Pain Associated in the Pose of a Patch of Capsaicine at High Concentration on the Carrier Patients of Localized Neuropathic Pains ? - DIDOCAP
Phase: NA
Conditions: Localized Neuropathic Pain
Sponsor: Centre Hospitalier Departemental Vendee

DIDOCAP 
                     
Version 5.0 of 15.01.2020  
  
  
  
  
  
  
  
  
  
  
"Does the application of cold reduce the pain associated with   
the application of a high concentration capsaicin patch in 
patients with pain   
localized neuropathic pain?"  
DIDOCAP study   
  
  
  
  
PROTOCOL OF   
RESEARCH IN ROUTINE CARE  
Nursing project  
  
Internal reference: CHD 049-16  
  
  
  
Person responsible for the research :   
  
Dr. Yves-Marie PLUCHON   
  
  
CETD Service   
  
  
  
  
  
  
  
Vendée Departmental Hospital Centre  
Secretariat: 02.51.44.62.48  
  
Responsible for the implementation of the research: Natacha TAILLIEZ,  
  
  
CETD Service   
  
  
  
  
  
  
  
Vendée Departmental Hospital Centre  
Secretariat: 02.51.44.62.48  
  
  
Manager :  
  
  
Centre Hospitalier Départemental Vendée  
  
Bd Stéphane Moreau  
  
85925 La Roche sur Yon  
  
  
Clinical Research Unit   
Vendée Departmental Hospital Centre  
Bd Stéphane Moreau  
85925 La Roche sur Yon  
  
  
  

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Signing of a research protocol in routine care page  
  
  
Internal reference: CHD 049-16  
Title: "Does the application of cold reduce the pain associated with the application of a high 
concentration capsaicin patch in patients with localised neuropathic pain?" DIDOCAP study  
  
  
  
The research will be conducted in accordance with the protocol and the legislative and 
regulatory provisions in force.  
  
Head of Research :  
  
Dr. Yves-Marie PLUCHON  
CETD Service  
CHD Vendée  
85925 La Roche sur Yon  
  
 
Date: .............../........./...........  
Signature :  
 
 
The promoter :  
  
Mr Francis SAINT-HUBERT  
General Management  
Vendee Departmental Hospital La 
Roche sur Yon  
  
 
Date: .............../........./...........  
Signature :  
 
Referent :  
  
Centre: .....................................  
  
Name: ............................................  
  
 
Date: .............../........./...........  
Signature :  
 
  
  
The research received a favourable opinion from the CPP Ouest VI in Brest on 26/07/2016. 

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TABLE OF CONTENTS  
I. Scientific justification, general description  
1. Name and description of the condition under study  
2. General description of the research  
3. Summary of the benefits, if any, and the foreseeable and known risks to the individuals involved in 
the research.  
4. Statement that the research will be conducted in accordance with the protocol and good clinical 
practice  
 
II Objectives  
1. Main objective  
2. Secondary objectives  
  
III Design and conduct of the research  
1. Clear statement of primary and, where appropriate, secondary evaluation criteria  
2. Description of the research methodology   
3. Description of measures taken to reduce and avoid bias  
4. Duration of participation for a subject in the research and a description of the timing and duration of 
all trial periods, including follow-up where appropriate  
5. Descriptions of the rules for permanent or temporary cessation  
6. Data collected  
  
IV Selection of persons   
1. Inclusion criteria  
2. Non-inclusion criteria  
 
V Products administered to research subjects  
1. Intervention under study  
2. Permitted treatments  
  
VI Statistics   
1. Description of the planned statistical methods, including the timing of planned interim analyses  
2. Expected number of people to be included in the research, and expected number of people in each 
research location with its statistical justification  
3. Expected level of statistical significance  
4. Method of accounting for missing data  
 
VII Right of access to source data and documents  
 
VIII Quality assurance 
 
IX Ethical assessments of the specific monitoring arrangements in the protocol  
 
X Data processing and retention of documents and data  
 
XI Insurance  
 
XII Rules on publication  
 
XIII References to scientific literature and relevant data used as a reference for the 
research  
   
 

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SUMMARY  
  
Title  
 "Does cold application decrease pain associated with high 
concentration capsaicin patching in patients with localised 
neuropathic pain?" DIDOCAP study  
Manager  
 Departmental Hospital Centre (CHD) Vendée - La Roche Sur Yon  
  
Head of Research  
Dr. Yves-Marie PLUCHON, CHD Vendée - La Roche sur Yon  
Responsible for the 
implementation of the 
research  
Natacha TAILLIEZ, nurse, CHD Vendée - La Roche sur Yon  
  
Population concerned  
 Patients treated for neuropathic pain    
  
Nature of the care assessed  
 Treatment of neuropathic pain with high concentration capsaicin 
patch  
  
Number of centres  
 4 centres/ 5 sites  
- CHD Vendée, La Roche sur Yon / Montaigu  
- Brétéché Clinic, Nantes  
- CH of Challans  
- Côte de Lumière Hospital, Les Sables D'Olonne  
  
Expected number of patients  
 100 patients randomised  
  
Main objective  
 To evaluate the effectiveness of cold application on pain reduction 
(burning sensation) after one hour of high concentration capsaicin 
patch (Qutenza®) in patients with localised neuropathic pain.  
  
Secondary objectives  
 To evaluate the efficacy of Qutenza® patch treatment on 
neuropathic pain in patients receiving cold application during 
placement.   
 Assess pain kinetics during the hour of application.  
 To evaluate the effectiveness of short-term cold application on 
the burning sensation.  
 To evaluate the reduction of the pain area 2 months after the  
 Quentza® patch in patients with localized neuropathic pain   
Inclusion criteria  
- 
 Male, Female  
- 
Major  
- 
Not objecting to participation in the study  
- 
Follow-up for localized neuropathic pain  
- 
Diagnostic score DN4 ≥ 4  
- 
Neuropathic pain in failure of conventional first-line treatment  
- 
To benefit from the first Qutenza® patch - Able to understand 
the proposed study   

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Non-inclusion criteria  
- 
 Patch application on feet, face, mucous membranes  
- 
Premedication with EMLA  
-Having already received a Qutenza® patch  
- 
Allergy to Qutenza® components   
- 
Known and poorly stabilised hypertension  
- 
known cryoglobulinemia  
- 
pregnant or breastfeeding woman  
- 
Patient benefiting from a legal protection measure 
(guardianship, curatorship...)  
- 
Patient deprived of liberty  
- 
Non-membership in a social security scheme. - Refusal to 
participate in the study   
Evaluation criteria  
 Primary endpoint  
- 
Collection of VAS (burning sensation) after 1 hour of 
Qutenza® patch application.  
  
Secondary evaluation criteria  
- 
Collection of the EVA (burning sensation) at 30 minutes of 
exposure,   
- 
Collection of VAS (neuropathic pain) before and 2 months 
after insertion,   
- 
Collection of DN4 score before and at 2 months after 
placement - Collection of pain (burning and neuropathic pain) by EN 
within one week of insertion,  
- 
Duration of burning sensation after application   
- 
Cold application during the week following the installation,  
- 
Taking painkillers in the week following insertion  
- 
Taking painkillers while applying the Qutenza® patch  
- 
Measurement of the painful area before patching and 2 months 
after patching  
  
Statistical methodology  
Prospective, randomised, two-centre, open-label nursing study.  
  
Patients will be randomized into two groups at the time of their first 
Qutenza insertion® :  
- 
Patient receiving Qutenza® without cold pack  
- 
Patient receiving Qutenza® in combination with a cooling pad  
Duration of a patient's 
participation   
2 months after the first Qutenza® patch application (post-first 
application consultation) - in practice this consultation is sometimes 
carried out up to 3 months after the application depending on 
availability and the organisation of the service.  
Timetable of the study  
Inclusion period: 42 months  
Duration of patient follow-up: 2 months (maximum 3 months allowed)  
Total duration of the research: maximum 45 months  
  
  

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LIST OF ABBREVIATIONS  
 
CCTIRS  
Advisory Committee on Information Processing in Health 
Research  
CETD  
Pain Assessment and Treatment Centre  
CHD Vendée  
Vendée Departmental Hospital Centre  
CNIL  
Commission Nationale Informatique et Libertés  
EMLA  
Eutectic mixture of local anesthetics  
EVA  
Visual Analogue Scale  
TRPV1  
Transient Receptor Potential Vanilloide 1  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 

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I SCIENTIFIC JUSTIFICATION, GENERAL DESCRIPTION   
  
1. NAME AND DESCRIPTION OF THE CONDITION UNDER STUDY  
  
Since 1994, neuropathic pain has been defined by the International Association for the Study of 
Pain (IASP) as "pain initiated or caused by a primary injury or dysfunction of the nervous 
system". More recently, it has been proposed to define neuropathic pain as "pain associated 
with injury or disease affecting the somatosensory system", but this definition has not yet been 
officially accepted.  
Neuropathic pain is often misunderstood, underestimated and under-treated. However, this pain 
is not rare, since, according to a recent epidemiological study in the general population, chronic 
pain with neuropathic characteristics affects 7% of the French adult population.  
  
These pains are due to a lesion of the peripheral nervous system (lesion of a nerve, a plexus, a 
nerve root) or central (lesion of the spinal cord, the brain stem, the thalamus).   
The causes can be traumatic, toxic, viral, tumoral or metabolic.  
The factors that lead to chronic pain can be professional, medico-legal, socio-economic, 
psychological, functional, etc.  
  
The diagnosis is based on a thorough interview and a well conducted clinical examination. The 
DN4 questionnaire, neuropathic pain in 4 questions, validated in French (5), is currently the 
reference tool for the diagnosis of neuropathic pain. (Appendix C).  
The patient suffering from neuropathic pain may experience tingling, intense tingling, electric 
shocks, a burning pain background, a compression sensation with numbness in the affected 
area.  
The repercussions of these pains are important on the quality of life: fatigue, anxiety, sleep 
disorders, depression.  
  
Neuropathic pain is unresponsive or poorly responsive to Tier I analgesics such as paracetamol 
and non-steroidal anti-inflammatory drugs. Other therapeutic classes should be considered.  
The first and most common treatment approach is to prescribe antidepressants or antiepileptics 
in moderate doses.  
These drugs have different side effects for different people.  
  
   
  
2 GENERAL DESCRIPTION OF THE RESEARCH  
  
« Capsaicin », extracted from the red pepper plant, has long been used therapeutically in the 
form of a cream at a low concentration requiring repeated applications and most often in 
postherpetic neuropathic pain.   
  

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Since pain is transmitted by neurotransmitters, the application of a patch soaked in this 
substance releases the conductive nerve fibres inflamed by excessive histamine and serotonin 
secretions. As a result, the pain may be greatly reduced, but the application of the patch is 
associated with an initial, unsustainable burning sensation.  
In the late 1990s, the improved knowledge of the TRPV1 (Transient Receptor Potential 
Vanilloid 1) receptors of the nociceptors, of which capsaicin is an agonist, and the specific work 
on neuropathic pain allowed the use of capsaicin to be reviewed.  
The availability to the medical profession of a highly concentrated 8% "trans-dermal device" 
form has changed practice.  
  
The long-term (3 months) efficacy of single applications of a high concentration (8%) capsaicin 
patch to the painful area (for 60 or 90 minutes) has been reported for postherpetic pain and 
painful HIV neuropathy(6,7,8)  
  
The interest of this treatment lies in the low risk of systemic side effects and the prolonged 
duration of effectiveness. However, the initial application, which is often very painful, requires 
monitoring of the patient, preferably in hospital, during application and the use of analgesics.   
  
At the CHD Vendée, QUTENZA®, capsaicin at 8%, has been used since 2012 in the treatment 
of peripheral neuropathic pain.  
The application protocol is as follows:  
The painful area must be determined by the doctor and marked on the skin. The patch should 
be applied to intact, non-irritated, dry skin. The Qutenza® patch is left in place for 60 minutes, 
and applications may be repeated every 60 to 90 days if pain persists or recurs. If necessary, the 
hair covering the area to be treated is trimmed short to promote adhesion of the Qutenza® patch 
(do not shave). The areas to be treated should be washed gently with soap and water. The patch 
of Qutenza® can be cut to the size and shape of the area to be treated, in this case it must be cut 
before removing the protective film.  
  
The application of the Qutenza® patch may progressively cause a burning sensation which may 
become intense due to the local inflammatory action of capsaicin. Then, after a few hours to a 
few days, the desired analgesic effect usually appears through an inactivation of the Cfibres, 
which suppresses the transmission of the pain message.  
  
Initially, it was recommended to prepare the area to be treated by applying a local anaesthetic, 
but the work of a German team (1) showed that this approach was of no interest as it had no 
real effect on the initial iatrogenicity of capsaicin.  
  
To reduce the burning sensation, a cooling procedure can be applied immediately after the patch 
is applied.  
  
According to the recommendations of the ASTELLAS laboratory, patients suffering from pain 
during and after the application of the patch may receive supportive treatment such as local 
cooling.  
  
Furthermore, the application of cold during the application of the capsaicin device does not alter 
the pharmacokinetics of the product. (1)  

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At the Centre d'Evaluation et de Traitement de la Douleur (CETD) in La Roche sur Yon, we 
applied this procedure and found a reduction in the burning sensation felt by a group of 90 
patients, half of whom did not have this cold application.  
The application of cold during the application of the capsaicin patch is already done in current 
practice, but there is still no real consensus, nor any study on the reduction of pain (burning 
sensation) nor on the effectiveness.  
Our hypothesis is that the application of cold during the application of the Qutenza patch® could 
decrease the patient's Visual Analogue Scale (VAS) (pain sensation) by 2 points.  
  
  
3. SUMMARY OF BENEFITS, IF ANY, AND FORESEEABLE AND KNOWN RISKS TO 
INDIVIDUALS INVOLVED IN THE RESEARCH  
  
There are no foreseeable risks associated with participation in the study. Patients will be 
managed according to standard practice.  
For patients receiving cold application, it will be necessary to protect the areas not treated by 
the patch but in contact with the cold with compresses to avoid the risk of cold burns.  
  
There was no direct predictable benefit for patients randomised to the no-cooling arm.  
  
On the other hand, the patient having received cold during the application should be less painful, 
he will not keep in memory this unpleasant memory (knowing that it is an area already 
presenting multiple painful symptoms) and will be ready to come back for a 2nd application. 
The patient's experience will therefore be better.  
  
4. STATEMENT THAT THE RESEARCH WILL BE CONDUCTED IN ACCORDANCE WITH 
THE PROTOCOL AND GOOD CLINICAL PRACTICE   
  
The investigator also undertakes that this research will be conducted :  
- in accordance with the protocol,  
- in accordance with current French and international good clinical practice.  
  
 II OBJECTIVES   
1. MAIN OBJECTIVE:   
  
To evaluate the effectiveness of cold application on pain reduction (burning sensation) after one 
hour of Qutenza® patch application in patients with localized neuropathic pain.  
  
Our hypothesis is that the application of cold during the application of the Qutenza patch® could 
decrease the patient's VAS (pain sensation) by 2 points.  
  
  
  

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2. SECONDARY OBJECTIVES:   
 To evaluate the efficacy of Qutenza® patch treatment on neuropathic pain in patients 
receiving cold application during placement.  
 Assess pain kinetics during the hour of application.  
 To evaluate the effectiveness of short-term cold application on the burning sensation. 
 To evaluate the reduction in pain area 2 months after Quentza® patching in patients 
with localised neuropathic pain   
III DESIGN AND CONDUCT OF THE RESEARCH  
1. CLEAR STATEMENT OF PRIMARY AND, WHERE APPROPRIATE, SECONDARY 
EVALUATION CRITERIA   
 Primary endpoint:  
- 
Collection of VAS (burning sensation) after 1 hour of Qutenza patch application® .  
In retrospective observations made at the CETD of the La Roche sur Yon Hospital, 70% of 
patients receiving a first Qutenza® patch reported more pain at 1 hour than at 30 minutes. 
For this reason, it was decided to evaluate the primary endpoint at 1 hour of application. 
Nevertheless, the pain at 30 minutes of application will be evaluated as a secondary endpoint.  
  
  
Secondary evaluation criteria :   
- 
Collection of VAS (neuropathic pain) before insertion and VAS (neuropathic pain) at 2 
months after insertion,  
- 
Collection of the DN4 score before and at 2 months after implantation.  
The DN4 questionnaire is used to estimate the probability of neuropathic pain. It is a score out 
of 10, if the patient's score is equal to or higher than 4/10 the test is positive.  
Although the DN4 questionnaire is a questionnaire for the diagnosis of neuropathic pain, it is 
also used in the participating centres for patient follow-up as it is a simple, easy-to-use scale 
that has become standard in all CETD consultations.  
This scale does not assess the intensity of pain, but its type and characteristics; equally important 
for patients in improving their quality of life. The DN4 can be compared before insertion and 
at follow-up. Pain intensity will be assessed via VAS.  
  
- 
Collection of the EVA (burning sensation) at 30 minutes of exposure.  
- 
Taking painkillers while applying the Qutenza® patch  
- 
Collection of pain (burning and neuropathic pain) by EN within one week of insertion,  
- 
Duration of burning sensation after application   
- 
Cold application during the week following the installation,  
- 
Taking painkillers in the week following insertion  
- 
Measurement of the painful area before patching and 2 months after patching  
  
 
 

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2. DESCRIPTION OF THE RESEARCH METHODOLOGY   
Feasibility :  
On retrospective observations carried out at the CETD of the CHD of La Roche sur Yon and 
at the CETD of the Clinique Brétéché in Nantes, the data of 124 patients were collected over a 
period of 16 months (non-exhaustive collection). Among these patients, 74 received a first 
Qutenza® patch (59.7%).  
Extrapolating these results and adding the Challans and Sables d'Olonne centres, we expect to 
obtain a potential of 100 patients over a 42-month period.  
Conduct of the study :  
  
This is a multicentre study on 5 different geographical sites (La Roche sur Yon, Montaigu, 
Challans, Nantes, Les Sables D'Olonne). It is planned to randomise 100 patients in total. In 
order to compensate for possible patients who would be included (signed non-objection) but 
could not be randomised, a maximum of 110 patients will be included. Enrolment will be 
completed once the study has reached 100 randomised patients.  
  
Approximately two months before the first Qutenza® patch is applied, the patient is seen in 
an information consultation by a doctor as part of their treatment at the CETD. On this 
occasion, a nurse will complete the consultation by presenting the DIDOCAP study and by 
proposing to the patient to participate.   
  
The patient will go home with the information leaflet. The patient's non-objection can be 
collected on the day of this consultation or at the latest on the day of the first patch of Qutenza®. 
The non-objection will be collected and signed by the doctor and/or the nurse.  
If the patient refuses, he/she will receive the most appropriate treatment for his/her situation 
(Qutenza patch® with or without the application of cold, at the discretion of the medical team 
and according to the patient's choice in accordance with the standard practice of the centres).  
  
If the patient accepts, a randomisation will be performed on the day of the Qutenza patch®  (via 
the e-CRF). The two randomisation groups are :  
- 
Patient receiving Qutenza® without cold application or  
- 
Patient receiving Qutenza® combined with cold application  
  
At each consultation (2 months before inclusion, on the day of inclusion (patching), at 1 month 
and at 2 months after patching) the patient will be seen by both a doctor and a nurse.  
Doctor: The doctor prescribes the Qutenza® patch, and carries out the tracing with the nurse 
on the day of application in the day hospital. He also prescribes painkillers for the week 
following the application if necessary.  
The doctor sees the patient again at 1 and 2 months.  
Nurse: The nurse greets the patient, assesses the pain, performs a global evaluation, gives 
information about adverse events related to the procedure, applies the patch according to the 
doctor's instructions following the Qutenza® patch use procedure.  

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 Cold application :  
  
The patch is applied by a nurse.  
 
 For patients randomised to the Qutenza® patch with cold application, cold application will be 
in the form of Actipoche® pads (reusable) provided by the sponsor for all participating sites.  
The Actipoche® cushion (placed in its cover) will be placed as soon as the application of the 
patch of Qutenza®  directly on the patch. If necessary, two Actipoche® cushions will be used to 
cover the entire area treated by the Qutenza® patches.  
Depending on the area treated, the cushions will be held in place either by a band (e.g. if the 
area treated is the knee) or by pressure (e.g. patient lying on his back for treatment of the 
scapula)   
  
In order to ensure the optimal temperature of the Actipoche® cushion, the Actipoche® 
cushion(s) will be replaced after 30 minutes with a new Actipoche® cushion for all patients.  
  
The Actipoche® cushion(s) will be removed at the same time as the Qutenza® patch after 1 
hour of application.  
  
The Actipoche® cushion can be used for both thermotherapy and cryotherapy.  
  
In cryotherapy: According to the product leaflet, it is recommended to place the Actipoche® 
cushion, without its cover, in the freezer for at least 20 minutes or in the refrigerator for about 
2 hours for optimal use.  
In the participating centres, the cushions will be placed in the freezer before application (i.e. at 
a temperature of approximately -6°C).  
 
To use: Insert the pouch into its cover and apply to the painful area for 20-30 minutes. Check 
the temperature of the cushion with the back of your hand before application.  
  
Between uses, the cushion can be stored either in the refrigerator or at room temperature.  
  
The leaflet states that analgesic or painkiller products can alter the perception of heat and cold 
in patients and that it is therefore not recommended to use the Actipoche® cushion in addition 
to this type of product.  
This precaution is intended to prevent possible misuse of the Actipoche® cushion during 
personal use at home.  
In the study, the Actipoche® cushion will be used in addition to the Qutenza® patch, which 
has a long-term analgesic action but is also associated with a strong burning sensation when 
applied.  
The perception of heat and cold will certainly be modified in patients, but this application will 
be carried out under medical supervision during the entire period of application.  
  
  
 
 
 

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Criteria assessed :  
  
The protocol consists of assessing the intensity of the burning sensation by means of a VAS at 
30 minutes and 60 minutes of exposure.   
  
It should be noted that the VAS evaluated before the Qutenza® patch, at 1 month and at 2 
months after application concern the patient's neuropathic pain, whereas the VAS at 30 and 60 
minutes are the pain related to the burning sensation.  
Concomitant treatment(s) received by the patient prior to the application of Qutenza® and in 
particular those taken on the day of application of the Qutenza® patch will also be collected.  
 
Patients will be reviewed in a medical consultation at 1 month and 2 months after insertion, 
according to standard practice. This last visit may be carried out at 2 months or at the latest at 
3 months after insertion, depending on the organisation and availability of the department.  
  
3. DESCRIPTION OF MEASURES TAKEN TO REDUCE AND AVOID BIAS   
Randomisation will be performed in an open-label fashion, according to 2 groups of patients: 
one group with cold application and another group without cold application on the Qutenza 
patch® . The randomisation will be stratified on the centre. It will be carried out according to a 
1:1 ratio and will be performed in blocks. Patients will be randomised on the day of application.  
  
Randomisation will be carried out via the Capture System software by connecting to the 
website: https://nantes-lrsy.hugo-online.fr/CSOnline/. 
The connection will be carried out thanks to a login, a password and a study number, 
delivered by the data manager of the CHD Vendée of La Roche sur Yon.  
The following information should be filled in:  
- 
First initial of the name,  
- 
First initial of the first name,  
- 
Month and year of birth,  
- 
Compliance with inclusion and non-inclusion criteria (yes/no), -  
No opposition 
to the study collected (yes/no).  
  
  
Randomisation will be carried out by the investigator after confirmation of the possibility of 
inclusion in the study and the collection of no objection.  
The inclusion number will be assigned automatically during randomisation. An email 
confirmation will be sent to the person who performed the randomisation and to all the 
persons concerned at the centre.  
  
The randomisation list will be drawn up by the study methodologist, Aurélie Le Thuaut, CHD 
Vendée before the start of the study. An explanatory guide to randomisation will be available 
online under Capture System.  
The randomisation list will be protected by restricted access and accessible only by the study 
biostatistician.  
  

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4. DURATION OF PARTICIPATION FOR A SUBJECT IN THE RESEARCH AND A  
DESCRIPTION OF THE TIMING AND DURATION OF ALL TRIAL PERIODS, INCLUDING 
FOLLOW-UP WHERE APPLICABLE  
  
The duration of a patient's participation will be 2 months from the day of the installation with a 
delay of up to 3 months depending on the availability and organisation of the service.  
  
5. DESCRIPTION OF THE PERMANENT OR TEMPORARY CESSATION 
RULES   
Subjects may withdraw their agreement to participate and request to be removed from the study 
at any time and for any reason. The investigator may temporarily or permanently discontinue a 
subject's participation in the study for any reason that is in the best interest of the subject.   
6. DATA COLLECTED 
See Annex A  
  
  
IV SELECTION OF PEOPLE   
All patients consulting the anti-pain centre of the CHD de Vendée, the Brétéché clinic, the 
Challans hospital, or the Côte de Lumière hospital in Les Sables d'Olonne for neuropathic pain 
requiring Qutenza® and meeting the inclusion criteria will be included in this study.  
1. INCLUSION CRITERIA   
- Male, Female  
- Major  
- Not objecting to participation in the study  
- Follow-up for localized neuropathic pain  
- Diagnostic score DN4 ≥ 4  
Neuropathic pain in failure of conventional first-line treatment  
- Expected to benefit from a first patch of Qutenza ®  
- Able to understand the proposed study  
  
2. NON-INCLUSION CRITERIA   
- Application of Qutenza® patches on the feet, face, mucous membranes  
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- Premedication with EMLA  
- Having already received a Qutenza patch®  
- Allergy to the components of Qutenza®  
- Known and poorly stabilised hypertension  
- known cryoglobulinemia  
- pregnant or breastfeeding woman  
- Patient benefiting from a legal protection measure (guardianship, curatorship,...)  
- Patient deprived of liberty  
- Non-membership in a social security scheme.  
- Refusal to participate in the study  
  
  
  
V PRODUCTS ADMINISTERED TO RESEARCH SUBJECTS  
  1. INTERVENTION UNDER STUDY  
Randomisation: application of cold or not during the application of the Qutenza patch® 
(transdermal anaesthetic device, active ingredient: capsaicin)  
  
For patients randomly selected in the group receiving the Qutenza® patch with cold application:  
-  Actipoche® cushion (reusable) provided by the promoter for all participating sites  
Ref : Laboratoire Cooper - Actipoche® Hot/Cold Large Size 20 x 30cm  
This is the brand of cushion currently used by the various participating centres.  
  
Composition : Gel based on : Propylene glycol - Sodium polyacrylate - Dye - Water. Plastic 
casing.  
  
  2. PERMITTED TREATMENTS  
As this is a routine care study, the management of the patient remains similar to standard 
practice. There are no prohibited treatments. The analgesic treatments taken by the patient will 
be noted in his or her observation book so that they can be taken into account in the analysis of 
the study.  
  
  

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VI STATISTICS  
1. DESCRIPTION OF THE PLANNED STATISTICAL METHODS, INCLUDING THE TIMING 
OF PLANNED INTERIM ANALYSES  
A descriptive analysis will be performed for all patient data overall and by randomisation arm. 
Quantitative variables will be described by mean, standard deviation, median, quartiles, extreme 
values. Qualitative variables will be described by the number of patients and the proportions 
according to the defined modalities.  
  
Main criterion  
  
The primary endpoint was the VAS collected 1 hour after the start of the procedure.  
The mean VAS between the 2 groups (with or without cold application) will be estimated and compared 
using a linear mixed model taking into account the stratification criterion on the centre. The "cold 
application" criterion will be taken into account as a fixed effect and the centre as a random effect.  
  
The main analysis will be "intention to treat". It may be supplemented by a "per-protocol" analysis. No 
intermediate analysis is planned.   
  
Secondary criteria  
  
VAS (neuropathic pain) before and at 2 months after surgery  
- The mean difference between the 2 groups (with or without cold application) will be estimated 
and compared using a linear mixed model taking into account the VAS score measured at 
baseline and the stratification criterion on the centre.  
  
DN4 before installation and at 2 months  
- The mean difference between the 2 groups (with or without cold application) will be estimated 
and compared using a linear mixed model taking into account the DN4 score measured at 
baseline and the stratification criterion on the centre.  
  
EVA (burning sensation) after 30 minutes  
- The mean VAS between the 2 groups (with or without cold application) will be estimated and 
compared using a linear mixed model taking into account the stratification criterion on the 
centre.  
The evolution of the pain at 30 minutes and 1 hour will be represented graphically.  
  
Short-term follow-up (7 days)  
- The mean NE between the 2 groups (with or without cold application) will be estimated and 
compared using a linear mixed model taking into account the stratification criterion on the 
centre.  
-The use of cold application during the week following the application will be compared 
between the 2 groups by a Chi2 test.  
 

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2. EXPECTED NUMBER OF PEOPLE TO BE INCLUDED IN THE RESEARCH, AND  
EXPECTED NUMBER OF PEOPLE IN EACH RESEARCH LOCATION WITH ITS  
STATISTICAL JUSTIFICATION  
Based on retrospective observations carried out at the CETD of the La Roche sur Yon hospital, 
on average, patients present a VAS pain of 7/10 one hour after application. We would like to 
reduce this pain to 5/10 (a reduction of 2 clinically relevant points) by applying cold during the 
application of the Qutenza patch .®)   
  
Assuming a decrease of 2 points between the initial VAS of the burn and the VAS at 1H, with a standard 
deviation of 2.8, an alpha risk of 5% and a power of 90%, 42 patients per group will be required. In 
order to compensate for possible dropouts, 50 patients per arm, i.e. 100 patients in total, will be 
randomised.  
In addition, in order to also accommodate possible patients who would be included (signed non-objection) but 
could not be randomised, a maximum of 110 patients will be included.  
Enrolment will be completed once the study has reached 100 randomised patients.  
  
3. EXPECTED LEVEL OF STATISTICAL SIGNIFICANCE  
The significance level is set at 5%.  
  
4.METHOD OF ACCOUNTING FOR MISSING DATA  
The number of missing data and the reason for the missing data will be described in each of the treatment 
groups.  
As the endpoint is collected one hour after patching, there will be no missing data on this endpoint.  
  
VII RIGHT OF ACCESS TO SOURCE DATA AND DOCUMENTS   
1. Access to data  
The medical data of each patient will only be transmitted to the organisation of the person 
responsible for the research or any person duly authorised by the latter under conditions that 
guarantee their confidentiality.   
  
2. Source documents  
Where appropriate, the responsible person's home organization may request direct access to the 
medical file for verification of research procedures and/or data, without breaching 
confidentiality and within the limits permitted by laws and regulations.  
  
  
 
3. Data privacy  

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Persons with direct access shall take all necessary precautions to ensure the confidentiality of 
information relating to the persons who have access, in particular as regards their identity and 
the results obtained.  
These persons, as well as the investigators themselves, are subject to professional secrecy 
(according to the conditions defined by articles 226-13 and 226-14 of the penal code). During 
or after the research, the data collected on the subjects and transmitted by the participants will 
be made anonymous.  
Under no circumstances should the names of the persons concerned or their addresses appear 
in clear text.   
Only the first letter of the subject's name and the first letter of the subject's first name will be 
recorded, along with the month and year of birth and a coded study number indicating the order 
of inclusion of subjects.   
  
VIII QUALITY ASSURANCE   
The research will be conducted according to the standard operating procedures of the 
management centre. The care of individuals in the participating centres will be carried out in 
accordance with medical ethics and recommendations.  
  
 IX ETHICAL ASSESSMENTS OF THE SPECIFIC MONITORING  
ARRANGEMENTS IN THE PROTOCOL  
As this is a routine care study, no therapeutic modifications will be made within the framework 
of the protocol. The occurrence of an adverse effect during the present protocol will give rise 
to a declaration in the appropriate vigilance system (pharmacovigilance, biovigilance, 
hemovigilance, materiovigilance, etc.).  
1. Committee for the Protection of Individuals  
The protocol and the information and no objection form for the study will be submitted to the 
CPP for advice.  
2. Substantial changes  
Any substantial modification to the study protocol must be notified to the Committee for the 
Protection of Individuals in order to verify that the proposed modifications do not alter at any 
time the guarantees provided to the persons who are to undergo the research. Information 
letter and no objection   
Patients will be informed fully and fairly, in understandable terms, of the objectives of the study, 
their rights to refuse to participate in the study or to withdraw at any time. All this information 
will be included on an information and opt-out form given to the patient.   

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X DATA PROCESSING AND RETENTION OF DOCUMENTS AND 
DATA  
1. Data entry   
One case report form (CRF) will be created per patient. All information required by the protocol 
must be provided in the CRF. The CRF will include the different steps of the patient's 
management in the protocol. It should include the data necessary to confirm compliance with 
the protocol, identify major deviations from the protocol and all data necessary for analysis.  
The anonymity of the subjects will be ensured according to the rules defined by the protocol.  
The data will be entered on a secure database and will only contain the patient's inclusion 
number as identity. The computer processing of the data is completely anonymous once the 
clinical collection has been completed.  
  
Patients are informed and informed that the results are available to them at the end of the 
analysis of this study if they request them.   
2.  CNIL  
This study falls within the scope of the "Reference Methodology" (MR-003) in application of 
the provisions of Article 54 paragraph 5 of Law No. 78-17 of 6 January 1978 on information 
technology, files and freedoms (updated and published in the official journal on 14 August 2016).    
  
3. Archiving  
Archiving of study documents will be done in accordance with Good Clinical Practice and 
the regulations in force.  
  
  
XI INSURANCE  
Insofar as the research is indeed qualified as Research in routine care by the CPP requested, 
which means that there is no additional risk linked to the study, the insurance will be that of the 
establishment responsible for the care (Article L. 1142-2).  
  
  
  
XII RULES ON PUBLICATION  
Scientific papers and reports related to this study will be produced under the responsibility of 
the principal investigator coordinating the study with the agreement of the responsible 
investigators. The co-authors of the report and publications will be the investigators and 
clinicians involved, in proportion to their contribution to the study, as well as the biostatistician 
and associated researchers.  

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The rules for publication will follow international recommendations (N Engl J Med, 1997; 
336:309-315).  
  
XIII REFERENCES TO THE SCIENTIFIC LITERATURE AND  
RELEVANT DATA USED AS A REFERENCE FOR THE RESEARCH   
1. 
Comparison of cooling and EMLA to reduce the burning pain during capsaicin 8% patch 
application: a randomized, double-blind, placebo-controlled study. KnolleE, Zadrazil 
M,Kovacs GG, Medwed S, Scharbert G, Schemper M. Pain. 2013 Aug 7  
  
2. 
Topical capsaicin for pain management: therapeutic potential and mechanisms of action 
of the new-high-concentrate capsaicin 8% patch. Anand P1, Bley K. Br J Anaesth. 2011 
Oct;107(4):490-502  
  
3. 
High-Concentration Capsaicin Patch (Qutenza® ) - A New Step in Treatment of 
Neuropathic Pain. Ana COBZARU, MD. Maedica (Buchar). Jan 2012; 7(1): 88-89.  
  
4. 
Tolerability of NGX-4010, a capsaicin 8% patch for peripheral neuropathic pain. John F 
Peppin,1 Kristine Majors,2 Lynn R Webster,3 David M Simpson,4 Jeffrey K Tobias,5 and 
Geertrui F Vanhove5 J Pain Res. 2011; 4: 385-392.  
  
5. 
Development and validation of the neuropathic pain symptom inventory. Bouhassira D 
et al. Pain 2004.  
  
6. 
Controlled trial of high-concentration capsaicin patch for treatment of painful HIV 
neuropathy. Simpson DM et al, NGX-4010 C107 Study Group. Neurology 2008;70:2305-13.  
  
7. 
A high concentration capsaicin dermal patch for lasting relief of peripheral neuropathic 
pain. Noto C et al. NGX-4010. Curr Opin Investig Drugs 2009;10:702-10.  
  
8. 
A High concentration capsaicin patch, for the treatment of postherpetic neuralgia: a 
randomised double-blind study. NGX-4010. Backonja M et al. Lancet Neurol 
2009;7,11061102.