Endoscopic Surgical Treatment of Rhino-Sinusal Mucormycosis

Study Overview
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Brief Summary
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Radical endoscopic transnasal surgery associated with medical treatment with liposomal amphotericine B may increase the local control of Rhino-Sinusal Mucormycosis and the survival rate. The objective of this study is to evaluate the local control rate and survival rate at 3 months after radical endoscopic transnasal surgery extended towards the skull base in association with antifungal therapy and early surgical reevaluation of the extent of the disease.

Detailed Description
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Introduction : Treatment of Rhino-Sinusal Mucormycosis remains a challenge because of the severity of the disease with high mortality rates. Mainly involving diabetic and immunodeficient patients, first clinical presentation is a common infection of the sinuses which can extend towards deep spaces of the face, orbits, the skull base and the brain. The mortality rates range from 20 to 50%, up to 80% in case of cerebral extension. through Transnasal Endoscopic Surgery extended to the Skull Base. Hypothesis : We hypothesize that infected tissues are devascularized and because of that antifungal therapies can hardly reach areas of infected tissues. Radical endoscopic transnasal surgery associated with medical treatment with liposomal amphotericine B may increase the local control of the disease and the survival rate. Clinical evaluation of the extent of the disease within the first 7 days following initial surgery may represent a prognosis factor. Methods : First national mutlicentric and multidisciplinary cohort on Rhino-Sinusal Mucormycosis Radiological staging for evaluation of the extent of the disease using CT scan, MRI and PET Scan at initial stage before surgery Radical surgery and/or endoscopic transnasal surgery extended towards the skull base associated with liposomal amphotericine B medical treatment. At day 7 new radiological evaluation and second surgical look to adapt surgical resection of infected tissues, perform biopsies to search for mycormycosis, biofilms and dosage of the concentration of liposomal amphotericin B inside tissues. New radiological and surgical looks in case of absence of local control obtained on the second look and further. Study of the response rate by an endoscopic & scan follow-up (with biopsies for anatomopathological et mycological studies) at 1 month, 3 months, 6 months & one year. PET scan initially & at 3 months. Number of subjects included : Phase II type trial (exclusion of a zero hypothesis of survival rate <50% ), N= 23 patients Total length of the study 4 years Inclusion period time : 3 years Time of participation per patient : 1 year Number of center and/or participating departments: 24 Mean number of patients included per year and per center : 0 to 3 patients

Official Title
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Treatment of Rhino-Sinusal Mucormycosis Through Transnasal Endoscopic Surgery Extended to the Skull Base.

Conditions
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Rhinocerebral Mucormycosis

Intervention / Treatment
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* Procedure: Multiple transnasal endoscopic surgeries


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man or woman, over 18 years old, presenting a mucormycosis on a sinus biopsy showing large filaments with non or little septae compatible with a mucoral or with a positive culture for a mucoral on a sinus sample associated to clinical head & neack anomalies (endoscopic) & scans compatible with a mucormycosis previous to the inclusion and this whatever the patient incumbent pathology. Patient treated by liposomal amphotericin B or just before being treated Signature of informed consent : by the patient if he is able to express their will by the family or close, if the patient is unable to consent Inclusion in emergency clause is possible ( CPP agreement ) if the patient is incapacitated , no close is present and that the surgery is urgent Person affiliated to a Health Security System (beneficiary) Exclusion Criteria: Pregnancy, breastfeeding Disseminated Mucormycosis (involvment of one site distant from the head and neck) Known hypersensitivity to a polyene Absence of documentation of mucormycosis (histological, mycological) Contraindication to the completion of the surgery as provided in this protocol Patient is the subject of a guardianship or tutelage measure

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Interventional Model Description: Endoscopic surgical treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multiple Surgeries<br>Patients undergoing transnasal endoscopic surgery | Procedure: Multiple transnasal endoscopic surgeries<br>* Transnasal endoscopic surgery extended to the skull base<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control rate and survival rate | To evaluate the local control rate and survival rate at 3 months after radical endoscopic transnasal surgery extended towards the skull base in association with antifungal therapy and early surgical reevaluation of the extent of the disease. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rates | Survival rates at 6 and 12 months | 6 and 12 months | 
| Study of the response rate | Study of the response rate at 1 and 3 months according to Segar criteria (Segal, Clin Infect Dis) using clinical, mycological and radiological evaluation. | 1 and 3 months | 
| Study of the local control | Study of the local control obtained at day 7+/-5 days and survival rate and response rate at 3 months. | 3 months | 
| Study of the association between local control and survival rate and response rate | Study of the association between local control obtained at 1 month and survival rate and response rate at 3 months. | 3 months | 
| Evaluation of the interest of CT PET scan | Evaluation of the interest of CT PET scan in studying clinical response at 3 months. | 3 months | 
| Radiological staging | Radiological staging: comparison of the initial extent of the mucormycosis at day 0 by CT scan and MRI and survival rate at 3 months and local control obtained at day 7. | 3 months | 
| Dosage of the amphotericin B concentration inside tissues | Dosage of the amphotericin B concentration inside tissues (infeusingcted and at the border of infected tissues) as obtained with biopsies at day 7. | Day 7 | 
| Search for biofilms using confocal microscopy | Search for biofilms using confocal microscopy on infected tissues biopsies | Day 0 and Day 7 | 
| Staging of sequellae | Staging of sequellae using quality of life questionnaires | 3 months, 6 months and 1 year | 
| Bank of mucormycosis tissues | Bank of mucormycosis tissues at -80°C | Day 0, Day 7, Day 14, D21 and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rhinocerebral Mucormycosis, Fungal Infection, Survival, Surgery