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

Tuberculosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01530568
• Other study ID #: TB Xpert ICU
• Status: Completed
• Phase: N/A
• First received: January 24, 2012
• Last updated: January 6, 2015
• Start date: August 2010
• Est. completion date: July 2013

Study information

• Verified date: January 2015
• Source: University of Cape Town
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Human Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 341
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Caregiver), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Other:
• Xpert
This arm receives the GeneXpert test
• Smear
This arm receives smear microscopy

Locations

Country	Name	City	State
South Africa	Groote Schuur Hospital, which operates within the Cape Town Central Health District of the Metro Region	Cape Town	Western Cape

Sponsors (1)

Lead Sponsor	Collaborator
University of Cape Town

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rates of TB treatment initiation	The proportion of patients on TB treatment in each arm will be compared longitudinally	48 hours	No
Secondary	Mortality in ICU	The time-specific proportion of patients who have died prior to discharge will be compared across arms	up to 2 months	No
Secondary	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	No
Secondary	ICU length of stay	The median ICU length of stay will be compared up to 3 months	up to 3 months	No