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AzTrials

TuberculosisNCT01693224

Feasibility of a Lateral Flow Urine LAM Test for Diagnosis of Tuberculosis in South Africa

A study testing Alere "Determine" lateral-flow urine lipoarabinomannan assay, Alere "Clearview" ELISA urine LAM assay and Cepheid Xpert MTB/Rif assay in people with Tuberculosis and Tuberculosis, Pulmonary, run by Tuberculosis Clinical Diagnostics Research Consortium at 2 sites in South Africa.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study is to evaluate the accuracy, diagnostic yield, operational performance, and time to diagnosis of a novel lateral-flow urine LAM test in detecting tuberculosis in HIV-infected adults. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alere "Determine" lateral-flow urine lipoarabinomannan assay, Alere "Clearview" ELISA urine LAM assay and Cepheid Xpert MTB/Rif assay
Type of treatment
Medical device
How many people
512 participants
Where
2 sitesSouth Africa
Study dates
Apr 2011to Feb 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

Inclusion Criteria (Individuals must meet all of the following inclusion criteria in order to be eligible to participate):

  • Informed consent
  • Suspected active tuberculosis
  • Willingness and ability to comply with study procedures
  • Any one or more of the following:
  • Current cough
  • Fever at any time within the preceding 4 weeks
  • Night sweats at any time within the preceding 4 weeks
  • Weight loss within the preceding 4 weeks
  • HIV-positive based on any one or more of the following:
  • written results of a positive HIV antibody test, and/or
  • written results of a positive HIV viral load, and/or
  • documentation in the medical record of positive HIV status by a treating clinician.

Exclusion Criteria (Any subjects meeting any of the following exclusion criteria at baseline will be excluded from study participation):

  • Multidrug tuberculosis treatment for greater than two days within the previous 60 days
  • Unwillingness or inability to provide a urine sample
  • Known chronic pulmonary condition, e.g. asthma, chronic obstructive pulmonary disease, emphysema
  • Respiratory distress, defined as respiratory rate of >30 or oxygen saturation <90%
  • Any specific condition that in the judgment of the investigator precludes participation because it could affect a subject's safety.

Trial locations and contacts

2 sites in 1 country.

South Africa2 sites

  • G.F. Jooste Hospital

    Cape Town, Western Cape

  • Town Two Clinic

    Cape Town, Western Cape

Other trials in South Africa

About this study

Official title: Feasibility of Using the Inverness Lateral Flow Urine LAM Test for Diagnosis of Tuberculosis in HIV-Positive TB Suspects in Cape Town, South Africa

The purpose of this study is to evaluate the accuracy, diagnostic yield, operational performance, and time to diagnosis of a novel lateral-flow urine LAM test in detecting tuberculosis in HIV-infected adults.

A secondary study objective is to evaluate the accuracy and diagnostic yield of the Cepheid Xpert MTB/Rif test in detecting tuberculosis in the blood of HIV-infected adults.

Read the detailed description

Background: Tuberculosis (TB) incidence and mortality have increased dramatically as a result of the HIV epidemic. In parts of sub-Saharan Africa, TB is the leading cause of death among HIV-infected patients and approximately 50% of TB patients are HIV co-infected. Early treatment of TB is hindered by the lack of rapid, accurate diagnostic modalities that can be applied in resource-constrained settings. Mycobacterial culture is the laboratory standard for diagnosis of active TB, but it is costly, requires access to specialized laboratories, and takes weeks to provide results. Sputum smear microscopy detects less than half of HIV-infected TB cases in many settings. The Global Plan to Stop TB has prioritized the development of simple, accurate, inexpensive tests for TB case detection in HIV-positive individuals.

LAM: As a strategy for rapid TB diagnosis, the detection of Mycobacterium tuberculosis antigens has been explored over several decades. Lipoarabinomannan (LAM), a glycolipid component of the outer cell wall of mycobacteria, is an attractive diagnostic target for several reasons: it is heat-stable; cleared by the kidney; detectable in urine; and as a bacterial product, has the theoretical potential to discriminate active TB from latent TB infection independent of human immune responses. A urine test could facilitate TB diagnosis in patients in whom sputum is uninformative or not obtainable, and lacks the infection-control risks associated with sputum production or blood collection. Urine LAM detection may be amenable to simple, rapid, inexpensive point-of-care platforms.

This is a prospective study to evaluate the accuracy, diagnostic yield, operational performance, and time to diagnosis of a novel lateral-flow urine LAM test in detecting tuberculosis in HIV-infected adults. HIV-positive adults suspected to have TB will be enrolled after providing informed consent. Urine will be obtained for testing using the novel lateral flow urine LAM assay and an existing ELISA-based urine LAM assay. Conventional microbiological tests for TB and chest x-rays will also be performed. These tests will be performed on all participants enrolled (target sample size = 500).

A secondary study objective is to determine the accuracy and diagnostic yield of the Cepheid Xpert MTB/Rif test in detecting tuberculosis in the blood of HIV-infected adults (the same set of participants on whom the LAM testing is done; approximate sample size = 500).

Being tested
Alere "Determine" lateral-flow urine lipoarabinomannan assay, Alere "Clearview" ELISA urine LAM assay, Cepheid Xpert MTB/Rif assay
Keywords
Tests, Diagnostic, Mycobacterium tuberculosis, Mycobacterium tuberculosis antigens, TB, Tuberculosis, Tuberculosis, Pulmonary, Tuberculosis, Miliary, Lipoarabinomannan
Medical subject headings
Tuberculosis, Tuberculosis, Pulmonary, Tuberculosis, Miliary, Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alere "Determine" lateral-flow urine lipoarabinomannan assayDevice

    Also called Determine lateral-flow urine LAM TB test

    lateral-flow (point-of-care) urine test to detect the lipoarabinomannan (LAM) component of the M. tuberculosis antigen in the urine of TB suspects, in vitro.

    Manufacturer: Alere

  • Alere "Clearview" ELISA urine LAM assayDevice

    Also called Clearview ELISA urine LAM TB test

    ELISA-based urine test to detect the lipoarabinomannan component of the M. tuberculosis antigen in the urine of TB suspects, in vitro.

    Manufacturer: Alere.

  • Cepheid Xpert MTB/Rif assayDevice

    Also called Cepheid Xpert MTB/Rif test

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Sensitivity of the lateral-flow urine LAM assay (LF-LAM)

    • Conventional TB tests (mycobacterial blood \& sputum culture) will be the reference standard used to calculate sensitivity of the LF-LAM test
    • Sensitivity is defined as TP/(TP+FN), or the number of true positives over (the number of true positives + the number of false negatives)
    • "true positive" = a positive LF-LAM result in a patient also having ≥1 culture positive for M. tuberculosis
    • "false negative" = a negative LF-LAM result in a patient also having ≥1 culture positive for M. tuberculosis

    Measured: One year

  2. Failure rate of the lateral-flow urine LAM assay

    Failure rate expressed as the proportion of lateral flow urine LAM tests that require repeating due to an unevaluable initial result

    Measured: One year

  3. Inter-reader variability of the lateral-flow urine LAM assay

    Expressed as the percent agreement

    Measured: One year

  4. Specificity of the lateral-flow urine LAM assay (LF-LAM)

    • Conventional TB tests (blood \& sputum culture) will be the reference standard used to calculate specificity (Sp) of the LF-LAM
    • Sp=TN/(TN+FP), or #true negatives / (#true negatives + #false positives)
    • "true negative" = negative LF-LAM in "Not TB" patient
    • "false positive" = positive LF-LAM in "Not TB" patient
    • "Not TB" = meets all criteria below
    • no sputum/blood culture positive for MTB
    • no smear microscopy positive for acid-fast bacilli
    • no granulomas/caseous necrosis on histopathology
    • no clinical response to TB treatment
    • a plausible alternative diagnosis

    Measured: One year

Secondary outcomes (7)

  1. Sensitivity of the ELISA-based urine LAM test

    • Conventional TB tests (mycobacterial blood \& sputum culture) will be the reference standard used to calculate sensitivity of the ELISA LAM test
    • Sensitivity is defined as TP/(TP+FN), or the number of true positives over (the number of true positives + the number of false negatives)
    • "true positive" = a positive ELISA LAM result in a patient also having ≥1 culture positive for M. tuberculosis
    • "false negative" = a negative ELISA LAM result in a patient also having ≥1 culture positive for M. tuberculosis

    Measured: One year

  2. Diagnostic yield (expressed as number of TB cases detected) of various diagnostic strategies (see description)

    Diagnostic yield will be measured for strategies including a) lateral flow urine LAM testing plus sputum smear microscopy; b) ELISA urine LAM testing plus sputum smear microscopy; c) sputum smear microscopy plus sputum culture; d) sputum culture plus mycobacterial blood culture.

    Measured: One year

  3. Time to diagnosis (expressed in days) of various diagnostic strategies (see description)

    Time to diagnosis will be measured for strategies including a) lateral flow urine LAM testing plus sputum smear microscopy; b) ELISA urine LAM testing plus sputum smear microscopy; c) sputum smear microscopy plus sputum culture; d) sputum culture plus mycobacterial blood culture.

    Measured: One year

  4. Accuracy, efficiency, costs, and cost-effectiveness of various combinations of TB diagnostic tests

    TB diagnostic tests to be included in this analysis: sputum smear microscopy, sputum culture, mycobacterial blood culture, chest X-ray, lateral-flow urine LAM testing, ELISA urine LAM testing, and Xpert MTB/Rif.

    Measured: One year

  5. Satisfaction of lateral-flow urine LAM test operators

    Based on questionnaire assessment

    Measured: One year

  6. Specificity (Sp) of the ELISA-based urine LAM test

    • Conventional TB tests (blood \& sputum culture) will be the reference standard used to calculate Sp of ELISA LAM
    • Sp=TN/(TN+FP), or #true negatives / (#true negatives + #false positives)
    • "true negative" = negative ELISA LAM in "Not TB" patient
    • "false positive" = positive ELISA LAM in "Not TB" patient
    • "Not TB" = meets all criteria below
    • no sputum/blood culture positive for MTB
    • no smear microscopy positive for acid-fast bacilli
    • no granulomas/caseous necrosis on histopathology
    • no clinical response to TB treatment
    • a plausible alternative diagnosis

    Measured: One year

  7. Sensitivity of the Xpert MTB/Rif test to detect MTB in blood

    Conventional mycobacterial blood culture will be the reference standard used to calculate sensitivity of Xpert MTB/Rif in blood

    • Sensitivity is defined as TP/(TP+FN), or the number of true positives over (the number of true positives + the number of false negatives)
    • "true positive" = a positive Xpert MTB/Rif result in a patient also having ≥1 mycobacterial blood culture positive for M. tuberculosis
    • "false negative" = a negative Xpert MTB/Rif result in a patient also having ≥1 mycobacterial blood culture positive for M. tuberculosis

    Measured: One year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2012 (estimated)
  2. Study startApr 2011
  3. Primary completionFeb 2013 (estimated)
  4. Study completionFeb 2013 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
512 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01693224
Sponsor's protocol ID
DMID 10-0051
Other IDs
NA_00043138
Status last verified
Sep 2012
First submitted
23 Sep 2012
Last updated
26 Sep 2012
Results posted
No
Data monitoring committee
No

Publications

  • Nakiyingi L, Moodley VM, Manabe YC, Nicol MP, Holshouser M, Armstrong DT, Zemanay W, Sikhondze W, Mbabazi O, Nonyane BA, Shah M, Joloba ML, Alland D, Ellner JJ, Dorman SE. Diagnostic accuracy of a rapid urine lipoarabinomannan test for tuberculosis in HIV-infected adults. J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):270-9. doi: 10.1097/QAI.0000000000000151.

    PubMed 24675585

Questions about this trial

What is this clinical trial studying?

A study testing Alere "Determine" lateral-flow urine lipoarabinomannan assay, Alere "Clearview" ELISA urine LAM assay and Cepheid Xpert MTB/Rif assay in people with Tuberculosis and Tuberculosis, Pulmonary, run by Tuberculosis Clinical Diagnostics Research Consortium at 2 sites 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?

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: status not confirmed, as of the sponsor's last update on 26 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Results are not available in the source record.

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?

Sensitivity of the lateral-flow urine LAM assay (LF-LAM) (time frame: One year). The study lists 4 primary outcomes in all. 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 NCT01693224, 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 26 Sep 2012.

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