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Endoscopic Surgical Treatment of Rhino-Sinusal Mucormycosis

Not Applicable
Terminated
Conditions
Rhinocerebral Mucormycosis
Interventions
Procedure: Multiple transnasal endoscopic surgeries
Registration Number
NCT02226705
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
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

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
11
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Multiple SurgeriesMultiple transnasal endoscopic surgeriesPatients undergoing transnasal endoscopic surgery
Primary Outcome Measures
NameTimeMethod
Local control rate and survival rate3 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 Outcome Measures
NameTimeMethod
Study of the response rate1 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.

Dosage of the amphotericin B concentration inside tissuesDay 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 microscopyDay 0 and Day 7

Search for biofilms using confocal microscopy on infected tissues biopsies

Survival rates6 and 12 months

Survival rates at 6 and 12 months

Study of the local control3 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 rate3 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 scan3 months

Evaluation of the interest of CT PET scan in studying clinical response at 3 months.

Radiological staging3 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.

Bank of mucormycosis tissuesDay 0, Day 7, Day 14, D21 and Day 28

Bank of mucormycosis tissues at -80°C

Staging of sequellae3 months, 6 months and 1 year

Staging of sequellae using quality of life questionnaires

Trial Locations

Locations (1)

Hôpital Lariboisière

🇫🇷

Paris, France

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