TuberculosisNCT01530568
Gene Xpert Diagnosis of TB Using Tracheal Aspirates From Intensive Care Unit (ICU) Patients
A study testing Xpert and Smear in people with Tuberculosis, run by University of Cape Town at 1 site in South Africa.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Xpert and Smear
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 341 participants
- Where
- 1 siteSouth Africa
- Study dates
- Aug 2010to Jul 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)).
Who cannot join
- 1. Patients known to have active TB or to already be on antituberculous medication.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Groote Schuur Hospital, which operates within the Cape Town Central Health District of the Metro Region
Cape Town, Western Cape, 7925
About this study
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
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.
Read the 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.
- Conditions
- Tuberculosis
- Being tested
- Xpert, Smear
- Keywords
- Intensive care, TB, tracheal aspirates, Gene Xpert
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XpertOther
This arm receives the GeneXpert test
SmearOther
This arm receives smear microscopy
| Study group | Role | What they receive |
|---|---|---|
| Smear | Active comparator | Routine microbiology based diagnostics for TB Receives: Other: Smear |
| GeneXpert | Experimental | Arm that will receive the Xpert test Receives: Other: Xpert |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rates of TB treatment initiation
The proportion of patients on TB treatment in each arm will be compared longitudinally
Measured: 48 hours
Secondary outcomes (3)
Mortality in ICU
The time-specific proportion of patients who have died prior to discharge will be compared across arms
Measured: 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
Measured: Up to 2 weeks
ICU length of stay
The median ICU length of stay will be compared up to 3 months
Measured: up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2012 (estimated)
- Study startAug 2010
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 341 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Keertan Dheda, University of Cape Town
- Investigators
- Keertan Dheda, PhD, Principal investigator, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01530568
- Sponsor's protocol ID
- TB Xpert ICU
- Status last verified
- Jan 2015
- First submitted
- 24 Jan 2012
- Last updated
- 7 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Calligaro GL, Theron G, Khalfey H, Peter J, Meldau R, Matinyenya B, Davids M, Smith L, Pooran A, Lesosky M, Esmail A, Miller MG, Piercy J, Michell L, Dawson R, Raine RI, Joubert I, Dheda K. Burden of tuberculosis in intensive care units in Cape Town, South Africa, and assessment of the accuracy and effect on patient outcomes of the Xpert MTB/RIF test on tracheal aspirate samples for diagnosis of pulmonary tuberculosis: a prospective burden of disease study with a nested randomised controlled trial. Lancet Respir Med. 2015 Aug;3(8):621-30. doi: 10.1016/S2213-2600(15)00198-8. Epub 2015 Jul 22.
PubMed 26208996
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01530568
- Acronym / sponsor ID
- TB Xpert ICU
- Conditions
- Tuberculosis
- Keywords
- Intensive care, TB, tracheal aspirates, Gene Xpert
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 341 participants (actual)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Study start
- Aug 2010
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 10 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Smear | Active comparator | Other: SmearRoutine microbiology based diagnostics for TB |
| GeneXpert | Experimental | Other: XpertArm that will receive the Xpert test |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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)).
Key exclusion criteria (1 listed)
- 1. Patients known to have active TB or to already be on antituberculous medication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XpertThis arm receives the GeneXpert test | Other | GeneXpert |
| SmearThis arm receives smear microscopy | Other | Smear |
Primary outcome
Rates of TB treatment initiation
Time frame: 48 hours
The proportion of patients on TB treatment in each arm will be compared longitudinally
3 secondary outcomes
Mortality in ICU
Time frame: up to 2 months
Duration of mechanical ventilation
Time frame: Up to 2 weeks
ICU length of stay
Time frame: up to 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2015.
- Derived from this study: PubMed 26208996Calligaro GL, Theron G, Khalfey H, Peter J, Meldau R, Matinyenya B, Davids M, Smith L, Pooran A, Lesosky M, Esmail A, Miller MG, Piercy J, Michell L, Dawson R, Raine RI, Joubert I, Dheda K. Burden of tuberculosis in intensive care units in Cape Town, South Africa, and assessment of the accuracy and effect on patient outcomes of the Xpert MTB/RIF test on tracheal aspirate samples for diagnosis of pulmonary tuberculosis: a prospective burden of disease study with a nested randomised controlled trial. Lancet Respir Med. 2015 Aug;3(8):621-30. doi: 10.1016/S2213-2600(15)00198-8. Epub 2015 Jul 22.
Related trials for Tuberculosis
RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
Tuberculosis
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keertan Dheda, PhD principal investigator
University of Cape Town
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Xpert and Smear in people with Tuberculosis, run by University of Cape Town at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rates of TB treatment initiation (time frame: 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01530568, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2015.