Clinical trial NCT02226705: Endoscopic Surgical Treatment of Rhino-Sinusal Mucormycosis
Official title: Treatment of Rhino-Sinusal Mucormycosis Through Transnasal Endoscopic Surgery Extended to the Skull Base.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Rhinocerebral Mucormycosis
Keywords: Rhinocerebral Mucormycosis
Surgery
Fungal Infection
Survival
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2014-08-27
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Endoscopic surgical treatment
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Local control rate and survival rate
timeFrame: 3 months
Secondary outcomes:
measure: Survival rates
timeFrame: 6 and 12 months
measure: Study of the response rate
timeFrame: 1 and 3 months
measure: Study of the local control
timeFrame: 3 months
measure: Study of the association between local control and survival rate and response rate
timeFrame: 3 months
measure: Evaluation of the interest of CT PET scan
timeFrame: 3 months
measure: Radiological staging
timeFrame: 3 months
measure: Dosage of the amphotericin B concentration inside tissues
timeFrame: Day 7
measure: Search for biofilms using confocal microscopy
timeFrame: Day 0 and Day 7
measure: Staging of sequellae
timeFrame: 3 months, 6 months and 1 year
measure: Bank of mucormycosis tissues
timeFrame: Day 0, Day 7, Day 14, D21 and Day 28
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Lariboisière
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Romain KANIA, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: