Clinical trial NCT03042754: Improve Treatment Outcomes for Tuberculosis Infection in Tertiary Care Hospitals
Official title: Improve Treatment Outcomes for Tuberculosis Infection in Tertiary Care Hospitals
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Tuberculosis
Keywords: LAM
XpertMTB/RIF
treatment outcome
Microbacterial tuberculosis
Lead sponsor: The HIV Netherlands Australia Thailand Research Collaboration
Sponsor class: OTHER
Collaborators: name: Chulalongkorn University
name: Bamrasnaradura Infectious Diseases Institute
name: Department of Medical Services Ministry of Public Health of Thailand
First posted: 2017-02-03
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Early diagnosis can contribute to good treatment outcomes and isolate infection control.

Detailed description: This study is conducted into 2 parts: prospective and retrospective.

The prospective study evaluated the use of Xpert MTB/RIF. The study was conducted at three large tertiary care hospitals: the King Chulalongkorn Memorial Hospital, Rajavithi Hospital and Bamrasnaradura Infectious Diseases Institute. Only pulmonologists and infectious disease physicians with extensive experience in TB participated in the study. Patients who had suspected PTB were enrolled into the study. Expectorated sputum were collected and transferred to the central laboratory, Chulalongkorn Research Center (CRC) Laboratory, King Chulalongkorn Memorial Hospital. Each sample was divided into two parts; one part for the Xpert MTB/RIF (Cepheid) and another part for mycobacterial culture. Drug susceptibility tests for streptomycin, isoniazid, rifampicin and ethambutol were performed with rapid qualitative procedure (BACTEC™ MGIT™ 960 SIRE Kit) and semi-automated system (BACTEC™ MGIT™ 960 System). Discordant results of MGIT and Xpert were retested with the rpoB gene sequencing system. All PTB patients were promptly treated with anti-TB drug regimens as WHO's recommendation. All patients had HIV testing done and CD4 cell counts were obtained for all HIV-infected patients. Antiretroviral treatment and prophylaxis for opportunistic infections were prescribed as standard treatment guideline for patients with HIV/TB co-infection. The patients were followed until completion of TB treatment or change in the diagnosis. The WHO definitions for cure, completed treatment, dead, default or treatment failure were used to define the outcome of treatment.

The authors , therefore, evaluated the utility of Xpert MTB/RIF in Thailand, prior to nation-wide implementation. In summary, our real-life cohort study use Xpert MTB/RIF for early diagnosis of PTB and rifampicin resistance in high TB burden country outside of the African region. The results may be beneficial for guiding the policy makers, especially the National Tuberculosis Programme (NTP) to control TB transmission, as the country move towards universal use of Xpert MTB/RIF.

The retrospective study assessed the urine LAM test which has not been evaluated in non-HIV-infected immunocompromised Asians with disseminated TB and non-disseminated TB (TB located in one organ) but has a poor sensitivity and specificity for detecting pulmonary TB patients without HIV infection. On that account, the authors evaluated the applicability and efficacy of TB diagnosis by using the urine from confirmed cultured TB cases with various immune response conditions, such as HIV-infected, non-HIV-infected and non-HIV-infected immunocompromised patients. The authors found that the sensitivity of the urine LAM in HIV-infected and non-HIV-infected patients were similar to previous reports. This confirmed that the urine LAM cannot be used alone to screen for TB. However, it can be used in conjunction with the culture and AFB smear test for patients co-infected with HIV with very low CD4 count. The urine LAM test is especially helpful in cases where the smear is negative in probable-TB patients. For this reason, the urine LAM test is attractive because it is not invasive, and the samples needed can be easily collected from these types of disseminated patients with and without HIV.

Aside from that, the urine LAM test can be used in those severely ill patients, regardless of HIV infection, where it is difficult to physically collect the sputum and paucibacillary samples. The PPV was over 80% for those infected with HIV and up to 100% in non-HIV-infected patients. For physicians, the PPV is more useful than the sensitivity and specificity of the assay because it will answer the question how likely the patient with a positive result from the urine LAM test will have TB or not. A high PPV can accurately guide the physicians to confidentially prescribe the TB medications which are crucial, especially among co-infected patients that are severely ill. For this reason, the urine LAM test seems to be a great point-of-care test that can easily be incorporated with the AFB smear and culture test for the Asian population. Furthermore, this study demonstrated that a positive urine LAM test result was significantly associated with death, especially those with HIV infection. This association is much stronger in patients with very low CD4 counts. The findings from this study suggest the possible use of the urine LAM test with the AFB smear and culture in resource-limited countries in diagnosing TB in advanced HIV and non-HIV-infected patients with TB. This promising diagnostic tool can increase the yield of TB diagnosis and predict the mortality rate of TB infection, particularly in advanced HIV patients.

Eligibility criteria: Inclusion Criteria:

* patients with suspected TB
* patients that can give us sputum and urine specimens

Exclusion Criteria:

* refuse to provide written informed consent

Primary outcomes:
measure: Sensitivity of sputum from patients suspected with TB
timeFrame: 2 years
measure: Sensitivity of urine LAM from patients suspected with TB
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Chulalongkorn University
city: Bangkok
country: Thailand
facility: HIV-NAT, Thai Red Cross AIDS Research Centre
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Institute
Study officials:
affiliation: Chulalongkorn University
name: Gompol Suwanpimolkul, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chulalongkorn University
name: Kamon Kawkitinarong, MD
role: PRINCIPAL_INVESTIGATOR
References: