Endoscopic Surgical Treatment of Rhino-Sinusal Mucormycosis

Rhinocerebral Mucormycosis Clinical Trial

— MICCA  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02226705
• Other study ID #: P110151
• Status: Terminated
• Phase: N/A
• Start date: January 2015
• Est. completion date: January 2021

Study information

• Verified date: April 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: January 2021
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mucormycosis
• Rhinocerebral Mucormycosis
• Zygomycosis

Intervention

Procedure:
• Multiple transnasal endoscopic surgeries
Transnasal endoscopic surgery extended to the skull base

Locations

Country	Name	City	State
France	Hôpital Lariboisière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Survival rates	Survival rates at 6 and 12 months	6 and 12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Search for biofilms using confocal microscopy	Search for biofilms using confocal microscopy on infected tissues biopsies	Day 0 and Day 7
Secondary	Staging of sequellae	Staging of sequellae using quality of life questionnaires	3 months, 6 months and 1 year
Secondary	Bank of mucormycosis tissues	Bank of mucormycosis tissues at -80°C	Day 0, Day 7, Day 14, D21 and Day 28