Rhinocerebral Mucormycosis
Conditions
Keywords
Rhinocerebral Mucormycosis, Surgery, Fungal Infection, Survival
Brief summary
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
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
Interventions
PROCEDUREMultiple transnasal endoscopic surgeries
Transnasal endoscopic surgery extended to the skull base
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Endoscopic surgical treatment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local control rate and survival rate | 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival rates | 6 and 12 months | Survival rates at 6 and 12 months |
| Study of the response rate | 1 and 3 months | Study of the response rate at 1 and 3 months according to Segar criteria (Segal, Clin Infect Dis) using clinical, mycological and radiological evaluation. |
| Study of the local control | 3 months | Study of the local control obtained at day 7+/-5 days and survival rate and response rate at 3 months. |
| Study of the association between local control and survival rate and response rate | 3 months | Study of the association between local control obtained at 1 month and survival rate and response rate at 3 months. |
| Evaluation of the interest of CT PET scan | 3 months | Evaluation of the interest of CT PET scan in studying clinical response at 3 months. |
| Radiological staging | 3 months | 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. |
| Dosage of the amphotericin B concentration inside tissues | Day 7 | Dosage of the amphotericin B concentration inside tissues (infeusingcted and at the border of infected tissues) as obtained with biopsies at day 7. |
| Search for biofilms using confocal microscopy | Day 0 and Day 7 | Search for biofilms using confocal microscopy on infected tissues biopsies |
| Staging of sequellae | 3 months, 6 months and 1 year | Staging of sequellae using quality of life questionnaires |
| Bank of mucormycosis tissues | Day 0, Day 7, Day 14, D21 and Day 28 | Bank of mucormycosis tissues at -80°C |
Countries
France
Outcome results
None listed