Additive Benefit of the Urine LAM Test to Current TB Diagnostics in HIV Positive Adults in Panama City, Panama

December 21, 2017 updated by: University of Florida

Investigating the Additive Benefit of the Urine Lipoarabinomannan Test to Current TB Diagnostics Among HIV+ Adults in Panama City, Panama

Tuberculosis (TB) is one opportunistic infection often seen in HIV individuals. In 2013, there were an estimated 31,800 HIV-TB co-infection cases and 6,100 HIV-related deaths due to TB in the Americas. Due to the non-specific nature of its clinical symptoms, TB can be confused with various diseases such as histoplasmosis, sarcoidosis, lymphoma, and pneumonia. In Panama, where Histoplasma capsulatum is endemic, diagnosing TB versus histoplasmosis based on clinical symptoms can be difficult. In Panama, approximately 7.65% of HIV patients are co-infected with histoplasmosis, and there is a 30% mortality rate in HIV-histoplasmosis patients in Latin America. Due to similar clinical features, misdiagnosis of active TB and disseminated histoplasmosis in endemic regions may lead to incorrect antibiotic management, which in turn results in unnecessary toxicity, antibiotic resistance, and monetary expenditures. The investigators interests lie in increasing TB diagnostic accuracy using a simple urine dipstick test and evaluating physician response to new diagnostic testing, in order to reduce misdiagnosis and improve health outcomes in the HIV population.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The gold standard for TB diagnosis, mycobacterial culture, is limited by a slow turnaround time, the need for skilled technicians and biosafety level 3 facilities. Another diagnostic test, Xpert MTB/RIF, produces same-day results, boasts a specificity of 98%, but is limited in the HIV population by its sensitivity of 67% (with a single sputum sample). High costs associated with this test have presented a major obstacle to its routine use (US$65,500 for a 16-module instrument, and US$9.98 to US$18.00 per cartridge). The urine lipoarabinomannan (LAM) Ag test has a specificity of 98.6% and a sensitivity of 66.7% in patients with a CD4 count below 50. LAM is a 17.5kD glycolipid and virulence factor of mycobacteria. The test's sensitivity improves in advanced HIV cases because of the higher bacillary burden, more frequent disseminated TB, and greater concentration of urine antigen due to less antigen-antibody formation, and HIV nephropathy. The test strip contains its own positive and negative controls for quality assurance, and can utilize fresh urine samples stored at room temperature for up to 8 hours after collection. In the right clinical setting, the urine LAM Ag test could have an important additive benefit in TB diagnosis in HIV individuals when combined with the current standards of care.

This study is investigating how physician management and patient outcomes change when the urine LAM test is added to the current TB diagnostic tests (mycobacterial cultures and occasional use of Xpert MTB/RIF). The national referral hospital in Panama, Hospital Santo Tomás, is an ideal study site given its dedicated HIV inpatient service and high TB and histoplasmosis burden. Histoplasmosis diagnosis is often based on clinical symptoms alone, and less frequently confirmed by skin or bone marrow biopsy. Due to diagnostic uncertainty, 40% of HIV patients with fever and cough receive dual TB and histoplasmosis therapy. Their current standard of TB care includes sputum AFB microscopy and culture. However, rapid results are only available for the sputum AFB, which has a sensitivity of approximately 30%. The urine LAM Ag test is not presently used there. When combined with the urine LAM Ag test, sputum AFB has a sensitivity of 25% (if CD4>200) to 72% (if CD4<50). Over the next year, investigators plan to study changes in physician diagnostic classification and management decisions before and after the introduction of the urine LAM Ag test. This information would not only aid in TB diagnosis, but also in the investigators understanding of how physicians integrate new information.

The main objective is to determine the effect of urine LAM Ag test results in reducing dual TB/histoplasmosis therapy, by comparing the rate and duration of dual therapy in the urine LAM group to a retrospective control group. The investigators second objective is to investigate barriers to incorporating the urine LAM Ag test and how the results impact physicians' approaches to treatment using a physician questionnaire.

A clinical trial study will be conducted using HIV positive patients from June 2016 to June 2017 who present with pertinent clinical criteria at Hospital Santo Tomás. Following urine LAM Ag test administration, results will immediately be provided to the treating physicians. The control group will consist of retrospectively selected patients from the Hospital Santo Tomás database who fit the same inclusion and exclusion, matched for age, sex, and clinical severity. Patient outcome data will be collected from the day of hospital admittance to their time of discharge. Following the conclusion of data collection, consenting physicians will be interviewed on benefits and barriers to incorporating the urine LAM Ag test within their practice.

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HIV positive adult, and
  • Admitted to Hospital Santo Tomas, and
  • history of fevers, and

  • Two or more of the following symptoms:

    • cough
    • shortness of breath
    • night sweats
    • weight loss
    • fatigue
    • loss of appetite

Exclusion Criteria:

  • Under 18 yrs of age, or
  • Already on TB therapy, or
  • Anuric

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Urine LAM Ag test
Patients will be enrolled prospectively and tested for TB using the urine LAM Ag test
Other: Urine LAM Ag test
TB diagnostic assay
No Intervention: Retrospective arm
Charts of retrospectively selected patients from the Hospital Santo Tomas database who presented within the last five years meeting inclusion criteria will be used as controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dual therapy duration
Time Frame: 1 Week
The number of days that anti-histoplasmosis and anti-tubercular medications are co-administered
1 Week
Physician questionnaire
Time Frame: 1 year
The questionnaire will be measured by Physician responses of Strongly Agree, Agree, Neutral, Disagree, or Strongly Disagree.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Creatinine change during hospitalization
Time Frame: 1 week
The change in baseline and peak creatinine levels during hospitalization
1 week
Number of diagnostic tests performed during hospitalization
Time Frame: 1 week
Number of diagnostic tests performed during hospitalization
1 week
Mortality during hospital stay
Time Frame: 1 week
Mortality during hospital stay
1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Florida

Collaborators

Hospital Santo Tomas

Investigators

  • Principal Investigator: Amy Y Vittor, MD PHD, University of Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

November 1, 2017

Primary Completion (Anticipated)

August 1, 2018

Study Completion (Anticipated)

August 1, 2018

Study Registration Dates

First Submitted

July 21, 2016

First Submitted That Met QC Criteria

September 21, 2016

First Posted (Estimate)

September 22, 2016

Study Record Updates

Last Update Posted (Actual)

December 26, 2017

Last Update Submitted That Met QC Criteria

December 21, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB201600869

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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