- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01525134
Feasibility of a Lateral Flow Urine Lipoarabinomannan (LAM) Test for Diagnosis of Tuberculosis
Feasibility of Using the Inverness Lateral Flow Urine LAM Test for Diagnosis of Tuberculosis in HIV-Positive TB Suspects
The purpose of this study is to evaluate the accuracy, diagnostic yield, operational performance, and time to diagnosis of a novel lateral-flow urine lipoarabinomannan (LAM) test in detecting tuberculosis in HIV-infected adults.
A secondary study objective is to determine the accuracy, efficiency, costs, and cost-effectiveness of various combinations of Tuberculosis (TB) diagnostic tests, including the novel Xpert MTB/Rif test.
Study Overview
Status
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, efficiency, costs, and cost-effectiveness of various combinations of TB diagnostic tests, including the novel Xpert MTB/Rif test. The Xpert MTB/Rif test will be performed on a subset of participants (approximately 200 participants out of the total of 500 participants we expect to enroll for the LAM component of the study.)
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Kampala, Uganda
- Infectious Diseases Institute, Makerere University
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Kampala, Uganda
- Mulago National Referral Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sensitivity of the lateral-flow urine LAM assay (LF-LAM)
Time Frame: One year
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One year
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Failure rate of the lateral-flow urine LAM assay
Time Frame: One year
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Failure rate expressed as the proportion of lateral flow urine LAM tests that require repeating due to an unevaluable initial result
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One year
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Inter-reader variability of the lateral-flow urine LAM assay
Time Frame: One year
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Expressed as the percent agreement
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One year
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Specificity of the lateral-flow urine LAM assay (LF-LAM)
Time Frame: One year
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One year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sensitivity of the ELISA-based urine LAM test
Time Frame: One year
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One year
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Diagnostic yield (expressed as number of TB cases detected) of various diagnostic strategies (see description)
Time Frame: One year
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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.
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One year
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Time to diagnosis (expressed in days) of various diagnostic strategies (see description)
Time Frame: One year
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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.
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One year
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Accuracy, efficiency, costs, and cost-effectiveness of various combinations of TB diagnostic tests
Time Frame: One year
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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.
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One year
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Satisfaction of lateral-flow urine LAM test operators
Time Frame: One year
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Based on questionnaire assessment
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One year
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Specificity (Sp) of the ELISA-based urine LAM test
Time Frame: One year
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One year
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Yukari Manabe, MD, Infectious Diseases Institute, Makerere University, Kampala, Uganda
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- DMID10-0001
- NA_00038297 (Other Identifier: Johns Hopkins Medicine Institutional Review Boards)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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