Gene Xpert Diagnosis of TB Using Tracheal Aspirates From Intensive Care Unit (ICU) Patients

Study Overview
=================
Brief Summary
-----------------
Aim: To evaluate the diagnostic utility and impact on patient outcomes of an automated PCR (Gene Xpert® MTB/RIF), in a group of patients with suspected pulmonary TB who are mechanically ventilated in ICU, using tracheal aspirates. Hypothesis: Gene Xpert is an accurate tool for the diagnosis of TB in the Intensive Care Unit and will impact on rates of treatment initiation and hospital stay.

Detailed Description
-----------------
Background Tuberculosis (TB) is a serious global public health emergency and there is a great need for the improvement of current diagnostic tools and the evaluation of newer and novel technologies for the rapid diagnosis of TB. The most common testing method for TB is sputum smear microscopy, which has remained largely unchanged in its sophistication and sensitivity. Smear microscopy detects around 50% of all active TB cases and is not capable of identifying drug resistance. Furthermore, even though culture is more accurate results are only available in several weeks. Treating patients empirically for TB exposes patients to the toxic side-effects of drugs, and if there is no response to treatment, raises the question of MDR-TB. These considerations apply to clinical decision-making in the ICU where TB is not infrequently encountered. A diagnosis of TB in this setting has important implications for drug-drug interactions, route of administration, and drug toxicity. The Gene Xpert® system's MTB/RIF Assay, an on-demand molecular test for simultaneous detection of Mycobacterium tuberculosis (M.tb) and rifampicin (RIF) resistance, has recently been released. This is the only system that combines on-board sample preparation with real-time PCR [1]. Helb and colleagues developed and performed the first analysis of the Cepheid Gene Xpert System's MTB/RIF assay. They evaluated the diagnostic utility of the system using sputum samples and showed that the system was highly sensitive and simple-to-use [2]. A recent paper (NEJM, 2010, in press) that enrolled almost 2000 patients found Xpert to have a sensitivity of almost 90% in smear-negative TB. However, how the test will perform when using tracheal aspirates is unknown. It is also unclear whether the test will have any impact in the ICU where the decision to treat is often made clinically and empiric treatment is initiated. To address these questions we aim to obtain tracheal aspirates from about 120 mechanically ventilated patients with suspected TB from the Groote Schuur Hospital Intensive Care Unit. Tests will be conducted at the Lung Infection and Immunity Unit laboratory (Groote Schuur Hospital, Cape Town) to evaluate the diagnostic utility of the Xpert® MTB/RIF Assay in this group of patients. The expected study period will be 12 months.

Official Title
-----------------
A Randomised Control Trial of a Standardised and User-friendly Real-time PCR Assay for the Diagnosis of TB Using Tracheal Aspirates Obtained From Patients in the ICU

Conditions
-----------------
Tuberculosis

Intervention / Treatment
-----------------
* Other: Xpert
* Other: Smear


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: 1. Any ventilated patients over 18 years of age with suspected TB (suggestive pulmonary infiltrates, a history of constitutional symptoms preceding the ICU admission, or patients known or suspected to be infected with the human immunodeficiency virus (HIV)). Exclusion criteria: 1. Patients known to have active TB or to already be on antituberculous medication.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Smear<br>Routine microbiology based diagnostics for TB | Other: Smear<br>* This arm receives smear microscopy<br>|
| Experimental: GeneXpert<br>Arm that will receive the Xpert test | Other: Xpert<br>* This arm receives the GeneXpert test<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of TB treatment initiation | The proportion of patients on TB treatment in each arm will be compared longitudinally | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality in ICU | The time-specific proportion of patients who have died prior to discharge will be compared across arms | up to 2 months | 
| Duration of mechanical ventilation | The median Duration of mechanical ventilation will be compared between arms prior to discharge up to 2 weeks | Up to 2 weeks | 
| ICU length of stay | The median ICU length of stay will be compared up to 3 months | up to 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Intensive care, TB, tracheal aspirates, Gene Xpert