Invasive Mould Infections in Indian ICUs - Descriptive Epidemiology, Management and Outcome

Mycoses Clinical Trial

Official title:

Invasive Mould Infections in Indian ICUs - Descriptive Epidemiology, Management and Outcome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02683642
• Other study ID #: FungalISF
• Status: Completed
• Phase: N/A
• First received: December 21, 2015
• Last updated: February 7, 2018
• Start date: April 2016
• Est. completion date: September 30, 2017

Study information

• Verified date: February 2018
• Source: Fungal Infection Study Forum
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Invasive mould infections are emerging causes of morbidity and mortality in ICU patients. This is attributed to prolonged ICU stay of critically ill patients with many co-morbidities. Modern medicine and multiple intervention make the patients susceptible to these prevalent moulds in the environment. In India the high frequency of IMIs in general has been attributed to environmental and host factors prevalent in this region. Additionally sub-optimal hospital care practice, frequent demolition and construction activities in the hospital make the patients susceptible to IMIs. There is no multicentric study available in India describing the epidemiology of IMIs in India. However, single center studies have reported distinct epidemiology of IMIs in India. High incidence, different spectrum and risk factors are possible unique features of IMIs in India.Early diagnosis and optimal therapy improve the outcome of these patients. The conventional diagnosis including histopathology and culture has limitations. The tests are of low sensitivity and long turnaround time. The major challenge is collection of sample from deep tissue. Therefore majority of the patients in ICUs of India are managed empirically against invasive fungal diseases. The galactomannan test has improved the diagnosis of invasive aspergillosis. However, galactomannan test is not well standardized in non-neutropenic patients. Beta-glucan test is used for early diagnosis of invasive fungal infections other than mucormycosis. But the test is cumbersome for routine laboratories and expensive. Both tests are not available in majority of Institutions of India. PCR assay is not standardized and not performed routinely in any Institution.

Due these limitations in diagnosis, there is no uniform management protocol in ICUs of India. To develop optimal management protocol, we need to know the epidemiology, the right patient to treat, antifungal drug resistance, optimal drug and duration of therapy etc. The present study will provide descriptive epidemiology, present status of diagnosis and management practiced in India to treat IMIs in ICUs. This will help to find the suitable intervention strategies to improve outcome of IMIs in India.This descriptive observational prospective study will document the epidemiologic and clinical characteristics, as well as treatment and outcome data, of patients with IMIs in ICUs in India over one year.

Description:

The prospective study will describe the epidemiology of IMIs in ICUs in India. The study will describe the incidence, risk factors, fungi causing IMIs and their susceptibility against antifungal agents, as well as the current strategies adopted by ICU physicians in the management of IMIs. It will also describe the outcome of IMIs. The study will help in planning future management strategies specific for IMIs in ICUs in India.

Methods

Study description: Prospective, multicenter study in iCUs in India.

Purpose: Determination of epidemiologic parameters, including risk factors, description of current management and outcome of patients with IMI will be recorded prospectively. The study will help in understanding the epidemiology of IMI in ICUs and possible planning for future management strategies for IMI specific to India.

Risk: There is no risk to the patient from the study as it is only an observational study and no intervention is intended.

Site selection: 15 ICU's are identified across the country where ICU physicians are well versed about invasive fungal infections and competent diagnostic mycology laboratory is available

A site feasibility survey was conducted. This ensured that participating sites fulfill the following inclusion criteria: a) maintains ICD coding and total number of discharges and deaths at the center; b) manages critically ill patients in ICU; c) has access to high-resolution CT (HRCT) scans; d) has a mycology laboratory that performs isolation and identification of fungi at least perform galactomannan test; and e) has histopathology facilities.

Study Period: April 1, 2016 to June 30, 2017. Case enrolment - April 1, 2016 to March 31, 2017. Analysis of data - April 1, 2017 to June 30, 2017

No. of patients: All consecutive patients with proven and probable IMI in ICUs at the study centers during the study period will be included.

Patient selection All consecutive patients diagnosed for proven or probable IMIs in ICUs at the study sites will be included.

Inclusion criteria:

Proven:

Histopathology/cytology/culture/direct microscopy demonstrating septate hyphae invading tissue or aspirate from sterile sites

Probable:

• Host satisfies host criteria of EORTC

• Host with COPD satisfying definitions by Bulpa P, et al Eur Resp J 2007

• Host in ICU satisfying clinical algorithm by Blot SI, et al Am J Resp Crit Care Med 2012

Exclusion criteria:

• Endemic mycoses (histoplasmosis, sporotrichosis, penicilliosis)

• Yeast infections

• Allergic fungal diseases like allergic bronchopulmonary aspergillosis

• Infection limited to the skin only

Conduct of the study

Investigators of the study: Arunaloke Chakrabarti will be the coordinator of the study. Each site will have a Principal Investigator - the site PI. Other investigators at the site will be co-investigators.

Patient enrollment: The site PI (or one of the co-investigators) will review the patient's paper and electronic records to determine if the patient satisfies the inclusion criteria. Patients who fulfill the inclusion criteria will be included as a case.

Data collection: The demographic, clinical, treatment and outcome data will be collected by investigator and email the form to the study coordinator, Arunaloke Chakrabarti. Outcome will be measured on day of discharge/death/30 and 120 days (whichever is earlier) after the diagnosis of the IMI. The date of diagnosis of an IMI is the day on which the diagnosis is defined as proven or probable. For cases that were enrolled as probable but subsequently became proven, the date of diagnosis is the earlier date. In addition, each center will also obtain data from its relevant hospital authority on the total number of discharges and deaths in ICUs for the period of April 1, 2016 to March 31, 2017.

Fungal isolates: All isolates from proven and probable IMIs will be sent to Mycology Reference Laboratory at PGIMER, Chandigarh for final identification and antifungal susceptibility testing

Patient management: The study will not interfere with patient management.

Statistics

The study will be analyzed using descriptive statistics. It is anticipated that the study will provide the following information:

• Incidence of IMI among patients in ICUs during the study period in the participating centers

• Relative frequency of each risk factor among IMI patients at the participating centers.

• Three-month survival of patients diagnosed with IMI.

• Other data the study should be able to generate will be in accordance with the objectives.

• Kaplan-Meier plots will be used to describe the survival of patients with IMI according to their underlying diagnosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: September 30, 2017
• Est. primary completion date: September 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion criteria:

Proven:

Histopathology/cytology/culture/direct microscopy demonstrating septate hyphae invading tissue or aspirate from sterile sites

Probable:

• Host criteria of EORTC

• Host with COPD satisfying definitions by Bulpa P, et al Eur Resp J 2007

• Host in ICU satisfying clinical algorithm by Blot SI, et al Am J Resp Crit Care Med 2012

Exclusion criteria:

• Endemic mycoses (histoplasmosis, sporotrichosis, penicilliosis)

• Yeast infections

• Allergic fungal diseases like allergic bronchopulmonary aspergillosis

• Infection limited to the skin only

Related Conditions & MeSH terms

• Mycoses

Locations

Country	Name	City	State
India	Sterling Hospital	Ahmedabad	Gujarat
India	St.Johns Medical College	Bangalore	Karnataka
India	Chirayu Medical College	Bhopal	Madhya Pradeh
India	PGIMER	Chandigarh
India	Sri Ramchandra Medical university	Chennai	Tamil Nadu
India	Nizams Institute Of Medical Sciences	Hyderabad	Telengana
India	AMRI Hospital	Kolkata	West Bengal
India	Tata Memorial Hospital	Mumbai	Maharashtra
India	Indraprastha Apollo Hospitals	New Delhi	Delhi
India	Sir Gangaram Hospital	New Delhi	Delhi
India	Christian Medical College	Vellore	Tamil Nadu

Sponsors (2)

Lead Sponsor	Collaborator
Fungal Infection Study Forum	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Invasive mould infections (IMIs) in Indian ICUs (Number of patients with IMI per 1000 ICU admissions)		Three months from the date of admission
Secondary	Incidence in specific population (Number of patients with IMI in specific population per 1000 ICU admissions)		six months after the completion of the study
Secondary	Mortality (number of deaths per 1000 ICU admissions)		six months after the completion of the study