Descriptive Epidemiology on Management of Mucormycosis
Condition: Mycoses
MeSH terms: Mycoses; Mucormycosis; Zygomycosis
Study type: Observational

Summary: 
      This is an observational chart review of all patients with confirmed and probable diagnosis
      of mucormycosis at 19 centers across Indian hospital. Data will collect using a standardized
      CRF. All collected data will be entered into a database prior to analysis. Broadly data will
      be collected on demography, clinical characteristics, diagnosis, treatment and outcome for
      each patient. Patient will continue to receive treatment as per treating physicians advise.
      Primary outcome for this study will be overall survival at 45 & 90 days.
    

Detailed description: 
      Introduction

      Mucormycosis is a life threatening angio-invasive fungal infection generally occurring in
      immunocompromised individuals. In recent years the incidence has increased globally and
      alarmingly in India especially in patients with uncontrolled diabetes. Mucormycosis is
      associated with very high morbidity and mortality. Mortality can be reduced with increased
      awareness of the disease, and aggressive medical and surgical intervention. Though few case
      series of mucormycosis are published from India, multiple gaps in knowledge exist regarding
      epidemiology, diagnosis and management of the disease in this country. It is therefore
      proposed to conduct this multicentric observational study in India to evaluate epidemiology,
      mode of diagnosis, management practices and outcome in patients with mucormycosis.

      Study Objectives

      Primary:

      - To describe the epidemiology, diagnosis, treatment practices and outcome of mucormycosis in
      India

      Secondary:

        -  Sites involved in mucormycosis

        -  Underlying disease and risk factors for mucormycosis

        -  Spectrum of agents causing mucormycosis Ð mode of diagnosis of mucormycosis

      Methods: Observation chart review Study Sites: We have assembled a network of health center
      across India called Mucormycosis Study Network (MSN), which consists of 19 centers across the
      country. Listed in Appendix 1.

      Study design: We propose to conduct a single arm prospective observational study.

      Study procedures:

      Working definition of Proven & Probable mucormycosis used for this study. Proven case:
      Presence of fungus in the tissue detected by direct microscopy (KOH, Calcoflor white) and
      Histopathological examination or from any aspiration /tissue from sterile site.

      Probable case: Clinical features of infection in organ-site with presence of mucorale in
      tissue from non-sterile infected site.

      Post enrollment, all patients will receive treatment as per the discretion of treating
      physicians or local hospital protocol. Data on patients' clinical features, risk factors,
      laboratory and radiological findings will be collected on standardize case report forms
      (CRF).

      Specifically, the extent of disease will be evaluated with appropriate radiological
      evaluation CT scan/ MRI (Brain, PNS, Thorax, abdomen etc.) Attempt will be made to collect
      follow up data till 6 months after diagnosis unless the patient lost in follow up or died
      before six months. All culture isolates will be sent to Mycology Reference Laboratory at
      PGIMER, Chandigarh for final identification and drug susceptibility testing. Blocks of
      histopathological specimen will be sent at reference mycology laboratory for patients with
      histopathological diagnosis of mucormycosis for DNA extraction and species identification.

      Primary outcome

        1. Overall survival at 45 & 90 days

        2. Cure: defined as complete resolution of clinical, radiological and mycological evidence

        3. Improved: Resolution of clinical features, radiological regression

      Secondary outcomes

      1. Grade III and IV toxicities of antifungal agents (Refer Appendix 2 for definition)

      Data Collection Data will collect using a standardized CRF. All collected data will be
      entered into a database prior to analysis. Broadly data will be collected on demography,
      clinical characteristics, diagnosis, treatment and outcome for each patient.

      Patient characteristics: Demographics, Comorbidities (Diabetes, Solid organ Transplant, GVHD
      requiring steroids, Febrile neutropenia, prolong neutropenia + Steroid therapy, Voriconazole
      exposure, Immunocompetent patient, Nosocomial [Surgical site, wooden spatula, ECG lead etc],
      history of road traffic accidents, tsunami, hurricane, Patients receiving immunosuppressives
      for collagen diseases, Use of monoclonal antibodies for treatment of variety of medical
      conditions, Iron overload and desferioxamine therapy, Burns patients), Organ dysfunction,
      Bacterial super infections

      Disease characteristics: Site of disease (pulmonary, PNS, Brain, skin and soft tissue, GI,
      Renal etc), number of lesions, species of mucormycosis

      Treatment:

        1. . Time to start antifungal drug after (a). Onset of disease i.e. first symptom (b).
           Diagnosis of mucormycosis

        2. . Dose and duration of antifungal agent

        3. . Time to Surgical Treatment after (a). Onset of disease i.e. first symptom (b).
           Diagnosis

        4. . Type of Surgical treatment: Radical surgery, Debridement, Repeated debridement
           Adjuvant treatment used e.g. Deferasirox, posaconazole

        5. . Posaconazole maintenance after completion of ABDC

      Outcomes:

      Overall survival (OS): OS will be measured 2 ways: from onset of first symptoms as reported
      by patient and from day of admission to last follow-up.

      Mortality Related to mucormycosis, not related to Mucormycosis

      Treatment Regimen:

      The study will not interfere with management at any stage. Treating physician will determine
      all process of patient management including diagnosis and treatment. Information on
      antifungal agent used, dosage used and duration of treatment will be collected.

      Information on surgical treatment will be collected i.e. time to surgical treatment after
      diagnosis, debridement, numbers and frequency of debridement, extensive surgical resection.

      Control of diabetes, reversal of metabolic parameters, management of immunosuppression will
      be noted.

      Follow up data will also be collected similarly.

      Patients will be assessed during hospitalization for drug compliance and toxicities.

      Adverse Event will be noted and graded according to standard grading system. Prior and
      Concomitant Therapy The details of any prior, concomitant or follow up therapy like
      deferasirox or Posaconazole will also be noted

      Statistical Plan Patient, disease and treatment characteristics will be summarized using
      descriptive statistics. Differences in the primary outcome of survival according to patient,
      disease and treatment characteristics will be assessed using a log-rank test and illustrated
      using the Kaplan-Meir analysis. Differences in OS will be summarized as hazard ratio along
      with 95% confidence intervals (CI). Differences in mortality and toxicities according to
      patient, disease and treatment characteristics will summarized as risk ratio along with 95%
      CI. All significance testing will be two sided and set at 5%.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        13 hospitals are identified across India for this study. All patients diagnose with
        confirmed and probable mucormycosis
      
Keywords: Mucormycosis