Antalgic Efficacy of CycloMesh™ Soaked in Ropivacaine Hydrochloride in Uncomplicated Inguinal Hernia.

Study Overview
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Brief Summary
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CycloMesh is a polyester visceral implant functionalized by drug delivery systems directly on its surface, targeting a unique intervention, a slow anesthetic release and an in situ activity. Based on the fact that cyclodextrins are capable of forming inclusion complexes with amino-amide anaesthetic agents, ropivacaine and cyclodextrins were combined on a commercial visceral mesh.This enables CycloMesh to release ropivacaine for a sustained period in order to improve patient's comfort after inguinal hernia surgery. The underlying hypothesis of this work is that clinical gain is achieved by adding a drug delivery system to visceral mesh for the local and prolonged delivery of ropivacaine. This should results in an improvement in quality of life, a reduction in pain and a faster returning to work following treatment of inguinal hernia by lichtenstein technique.

Official Title
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Interventional Study of Antalgic Efficacy of the CycloMesh™ Implant Soaked in Ropivacaine Hydrochloride 10 mg/mL in the Treatment of Uncomplicated Inguinal Hernia. Randomized Comparative Study Versus CycloMesh™ Soaked in Physiological Saline Solution NaCl 9°/°°

Conditions
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Inguinal Hernia

Intervention / Treatment
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* Procedure: Inguinal hernia repair with CycloMesh™ soaked in ropivacaine hydrochloride 10mg/mL
* Procedure: Inguinal hernia repair with CycloMesh™ soaked in saline solution NaCl 9°/°°


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease-related criteria: Uncomplicated and non-recurrent unilateral symptomatic inguinal hernia with a surgical indication Bilateral inguinal hernia symptomatic on one side and requiring surgery on the symptomatic side Symptomatic, normal unilateral inguino-scrotal hernia (located above the middle of the inner thigh), uncomplicated and non-recurrent, with an indication for surgery by local inguinal approach without testicular redonation. Open surgery with Lichtenstein's technique; Programmed outpatient surgery; Surgery performed under general anesthesia. Population-related criteria: Male subjects over 18 years old; Subjects who have given their free informed signed consent to participate in the study; Subjects who are affiliated to a social security system or have rights from a social security system. Non inclusion Criteria: Disease-related criteria: Strangulated inguinal or inguino-scrotal hernia; Bilateral inguinal hernia symptomatic on both sides and requiring surgery on both sides Chronic pain state (> 3 months) and/or long term analgesics intake susceptible to hide or interfere with pain assessment; Hepatic or renal failure and any other pathology that could notably extend half-life of anaesthetics and analgesics products Signs of infection at the surgical site; Severe cardiopulmonary, hepatic or renal diseases Active ongoing malignant disease; Product or device-related criteria: Known allergy or hypersensitivity to any of the constituents of the CycloMesh (Polyethylene terephthalate + Cyclodextrin) and/or subjects allergic to ropivacaine; Allergy to any drugs of the anesthesia protocol; Population-related criteria: Drug or alcohol abuse (addiction: i.e. chronic alcoholism or active drug addiction) Daily intake of level I analgesics (Paracetamol, Aspirin, Ibuprofen...etc.), for > 6 weeks. Use of corticosteroids within 24 hours prior to the surgery. Chronic use of antidepressants, anxiolytics, neuroleptics since 1 month or more, In case of occasional use, taking antidepressants, anxiolytics, neuroleptics in the 72 h prior to the intervention Unavailability during the study Participation in a clinical trial within 3 months prior to the initial visit. Psychiatric pathology or depressive disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CycloMesh™ soaked in ropivacaine hydrochloride 10mg/mL<br>The surgical technique for the inguinal hernia repair is the surgeon's usual technique: open surgery (Lichtenstein technique). CycloMesh™ device (soaked in ropivacaine hydrochloride 10mg/mL) is positioned once the surgery for the inguinal hernia repair has been performed. | Procedure: Inguinal hernia repair with CycloMesh™ soaked in ropivacaine hydrochloride 10mg/mL<br>* The surgical technique for the inguinal hernia repair is the surgeon's usual technique: open surgery (Lichtenstein technique). CycloMesh™ device (soaked in ropivacaine hydrochloride 10mg/mL) is positioned once the surgery for the inguinal hernia repair has been performed.<br>|
| Active Comparator: CycloMesh™ soaked in saline solution 9°/°°<br>The surgical technique for the inguinal hernia repair is the surgeon's usual technique: open surgery (Lichtenstein technique). CycloMesh™ device (soaked in saline solution) is positioned once the surgery for the inguinal hernia repair has been performed. | Procedure: Inguinal hernia repair with CycloMesh™ soaked in saline solution NaCl 9°/°°<br>* The surgical technique for the inguinal hernia repair is the surgeon's usual technique: open surgery (Lichtenstein technique). CycloMesh™ device (soaked in saline solution) is positioned once the surgery for the inguinal hernia repair has been performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity after treatment of inguinal hernia by lichtenstein technique under general anesthetic will be assessed 6h post-operative using Visual Analogic Scale (VAS). | The visual analogue scale is a graduated ruler from 0 to 10 cm where 0 indicates that the subject has no pain and 10 cm represents the maximum pain the subject can tolerate. It is a self-assessment scale and is sensitive, reproducible, reliable and validated for both acute and chronic pain situations. Pain assessment will be performed 6 hours after implant placement and during cough effort. | 6 hours post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity back to home (Day 0) and Day 1 to 3 will be assessed using a Visual Analogic Scale (VAS) | Pain intensity will be reported by the patient on a log book using a Visual Analogic Scale . The visual analogue scale is a graduated ruler from 0 to 10 cm where 0 indicates that the subject has no pain and 10 cm represents the maximum pain the subject can tolerate | Back to home (Day 0) at 8pm and 10 pm, Twice a day (8 am and 8 pm) at Day 1, Day 2 and Day 3 | 
| Pain intensity at Day 1 and Day 7 post-surgery will be assessed using a Visual Analogic Scale (VAS) | Pain intensity at Day 1 and Day 7 post-surgery will be assessed using a visual analogic scale and during a telephone interview performed by an investigator's collaborator. The visual analogue scale is a graduated ruler from 0 to 10 cm where 0 indicates that the subject has no pain and 10 cm represents the maximum pain the subject can tolerate.It is a self-assessment scale and is sensitive, reproducible, reliable and validated both in acute pain and chronic pain situations. | Day 1 and Day 7 post-surgery | 
| Pain intensity at 1 month post-surgery will be assessed using a Visual Analogic Scale (VAS) | Pain intensity at 1 month post-surgery will be assessed, using a visual analogic scale, during a visit to the surgeon and in 3 different situations: at rest, walking and during cough effort.The visual analogue scale is a graduated ruler from 0 to 10 cm where 0 indicates that the subject has no pain and 10 cm represents the maximum pain the subject can tolerate.It is a self-assessment scale and is sensitive, reproducible, reliable and validated both in acute pain and chronic pain situations. | 1 month post-surgery | 
| Hospitalization lenght (in hours) | In case of delayed discharge (the day after the surgery or prolongation of hospitalization), the reasons of prolonged hospital treatment will be collected | 1 week post-surgery | 
| Duration of surgical time from the first incision until wound closure (in minutes) | Duration of surgical time from the first incision until wound closure will be calculated in minutes | At the moment of wound closure | 
| Evolution between inclusion and 24 months post-surgery with regard to quality of life | Quality of life will be assessed using the 36-item Short Form Health Survey (SF-36) score at inclusion and 1 month post-surgery: SF-36 is a standardized and validated questionnaire assessing quality of life. The SF-36 provides two scores: a mental and social quality of life score and a physical quality of life score | Inclusion and 1 month post-surgery 12 and 24 months post-surgery | 
| The amount of consumed analgesic will be assessed using post-operative data and data reported by the patient on a log book | The amount of consumed analgesic will be measured by calculating the number of patients who have consumed analgesic during the 7 post-operative and antalgic intake (in mg) during the 7 post-operative | 7 days post-surgery period | 
| Time to return to work or activity post-surgery | The Time to return to work or activity following surgery will be evaluated in terms of the number of days between hospitalisation and resumption of activity | Day 1, Day 7 and 1 month post-surgery | 
| The rate of early recurrence (at 1 month postoperative) and at long term (12 and 24 months) will be assessed | Rates of early reccurence during the study (up to one month after surgery). The long-term recurrence rate will also be assessed at 12 and 24 months post-operatively. Recurrence is defined as the reappearance of the hernia on the same side as the one initially operated on, whether the recurrence required surgical intervention. | All study period (24-months) | 
| Number of patients presenting at least one adverse event (AE) | The safety and tolerability end points will be will be as follows: number of patients presenting at least one adverse event (AE) | All study period (24-months) | 
| Number of patients presenting at least one AE related to the the device implantation | The safety and tolerability end points will be will be as follows: number of patients presenting at least one AE related to the the device implantation | All study period (24-months) | 
| Number of patients presenting at least one serious adverse event (SAE) | The safety and tolerability end points will be will be as follows: number of patients presenting at least one serious adverse event (SAE) | All study period (24-months) | 
| Total number of AE related to the device implantation, classified by type and organ | The safety and tolerability end points will be will be as follows: total number of AE related to the device implantation, classified by type and organ | All study period (24-months) | 
| Satisfaction of the surgeon and unit staff regarding the use of CycloMesh will be evaluated using a satisfaction questionnaire | Surgeon and unit staff will have to answer to a questionnaire concerning the packaging of CycloMesh, the technical characteristics of the implant (flexibility, porosity, etc.), its size, time imbibition of CycloMesh, etc. | Day 0 | 
| Pain intensity after treatment of inguinal hernia by lichtenstein technique under general anesthetic will be assessed 6h post-operative using Visual Analogic Scale (VAS). | The visual analogue scale is a graduated ruler from 0 to 10 cm where 0 indicates that the subject has no pain and 10 cm represents the maximum pain the subject can tolerate. It is a self-assessment scale and is sensitive, reproducible, reliable and validated for both acute and chronic pain situations. Pain assessment will be performed 6 hours after implant placement at rest and walking | 6 hours post-surgery | 
| The rate of patient with chronic pain at 12 and 24 months | Chronic pain is defined as pain that lasts for at least 6 months after surgery | 12-months after surgery and 24-months after surgery | 
| The rate of implant migration at 12 and 24 months | Migration is defined as the movement of the entire implant into an organ. | 12-months after surgery and 24-months after surgery | 
| The rate of foreign body sensation at 12 and 24 months postoperative | Foreign body sensation is assessed by answering yes or no to the question: do you feel a foreign body in the groin | 12-months after surgery and 24-months after surgery |