Effect of Xpert MTB/RIF on Patient Outcomes

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ClinicalTrials.gov Identifier: NCT02729532

Recruitment Status : Completed

First Posted : April 6, 2016

Last Update Posted : April 22, 2019

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

National Institutes of Health (NIH)

Information provided by (Responsible Party):

University of North Carolina, Chapel Hill

Study Description

Brief Summary:

A parallel-group prospective cohort study among adult persons living with HIV/AIDS to study the effect of a new TB diagnostic test, Xpert MTB/RIF on: 1) TB case detection; 2) time to TB diagnosis and TB treatment; 3) presumptive TB patient drop-out from the TB diagnostic "cascade" before starting TB treatment; and 4) loss to follow-up after initiation of TB treatment.

Condition or disease	Intervention/treatment
Tuberculosis	Device: Xpert

Detailed Description:

The Centre for Infectious Disease Research in Zambia (CIDRZ) in collaboration with the Zambian National TB Program (NTP) and the Ministry of Health (MOH) will provide near point-of-care Xpert testing at a high-volume anti-retroviral treatment (ART) clinic in Lusaka, Zambia. A total 892 study participants will be enrolled into two parallel cohorts-an "Xpert" and a "standard of care" (SOC) cohort over a 7-month period. The Xpert cohort will enrol participants at the health centre implementing Xpert. The SOC cohort will enrol participants from one health centre offering the standard of care (sputum smear microscopy plus clinical evaluation). A parallel-group prospective cohort study will be conducted by following participants in one cohort from each site for 210 days from the time of sputum submission, allowing sufficient person-time to observe all outcomes of interest, including completion of a standard course of ATT as well as patient drop-out and loss to follow-up.

A systematic facility assessment survey using an adapted version of the WHO Service Availability and Readiness Assessment tool will be conducted. Key informants will be interviewed.

Study Design

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Study Type :	Observational
Actual Enrollment :	776 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Z 31411 - The Effect of Xpert MTB/RIF on Patient Health Outcomes and Empirical TB Treatment Among Persons Living With HIV/AIDS: A Parallel-Group Prospective Cohort Study Under Real-World Conditions in Lusaka, Zambia
Actual Study Start Date :	June 22, 2016
Actual Primary Completion Date :	February 9, 2018
Actual Study Completion Date :	February 9, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Tuberculosis

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Xpert cohort HIV-positive presumptive TB patients tested for TB using Xpert MTB/RIF assay (fluorescence microscopy and TB culture also done to serve as reference standard)	Device: Xpert The Xpert MTB/RIF assay is a nucleic acid amplification (NAA) test that uses a disposable cartridge with the GeneXpert Instrument System Other Name: Xpert MTB/RIF assay
Standard of Care cohort HIV-positive presumptive TB patients tested for TB using standard of care testing (sputum smear microscopy plus clinical evaluation)

Outcome Measures

Primary Outcome Measures :

Culture-positive patient drop-out before accessing treatment [ Time Frame: From study enrolment through confirmed drop out date at or before 210-days post enrollment ]
For both cohorts, the proportion of patients not started on TB treatment by 210 days post-enrolment will be assessed.

Secondary Outcome Measures :

Time to TB treatment [ Time Frame: time in days from study enrolment to initiation of anti-TB therapy (ATT) (through 210 days post-enrolment) ]
Percentage of participants who receive TB treatment within 14 days of enrolment (effect of Xpert on the accuracy of TB diagnosis) [ Time Frame: study enrolment to 14 days of enrolment ]
sensitivity of empirical TB diagnosis and treatment will be defined as the percentage of participants who received TB treatment within 14 days of enrolment among all those with a positive culture but negative or unavailable result for SM (for the SOC cohort), or negative or unavailable SM plus Xpert (for the Xpert cohort)
Percentage of participants who did not receive TB treatment 14 days post-enrolment (effect of Xpert on the accuracy of TB diagnosis) [ Time Frame: study enrolment to 14 days of enrolment ]
the specificity of empirical treatment will be defined as the percentage of participants who did not receive TB treatment 14 days post-enrolment among all those with a negative culture and negative or unavailable result for SM (in the SOC cohort), or negative or unavailable result for SM plus Xpert (in the Xpert cohort)
Time to TB Diagnosis [ Time Frame: average of 28 days ]
The World Health Organization definition of a TB case will be used
Number of TB patients lost to follow-up [ Time Frame: The number of patients will be measured as time in days from study enrolment to confirmed drop out (confirmed as failure noted at 3 and 6 month chart review) ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Adult presumptive TB patients 18 years or older with documented HIV-positive sero-status presenting for routine HIV care at two health centres in Lusaka, Zambia.

Criteria

Inclusion Criteria:

Able to spontaneously expectorate at least 2 sputum samples, in accordance with NTP guidelines
Intend to continue receiving care at the respective study sites for at least 7 months
Willing to provide locator information and allow contact by phone or home visit in the case of loss to follow up after initiating ATT

Exclusion Criteria:

Received TB treatment within 60 days prior to enrolment and/or were diagnosed with TB within the last 6 months
Cannot spontaneously expectorate sputum
Are already enrolled in another study with might interfere with implementation of this study protocol
Provided a sputum sample that results in a contaminated TB culture result

A key informant will be eligible for inclusion in the SARA facility survey component of the study if they meet the following criteria:

18 years of age or older
clinic staff member at either Chilenje Health Centre or Chelstone Health Centre
have previously been attached to, or are otherwise familiar with, departments offering HIV, TB and/or laboratory health services

Exclusion criteria:

-unwilling or unable to provide verbal informed consent in English

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02729532

Locations

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Zambia
Chelstone and Chilenje Health Centres
Lusaka, Zambia

Sponsors and Collaborators

University of North Carolina, Chapel Hill

National Institutes of Health (NIH)

Investigators

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Principal Investigator:	Michael Herce, MD, MPH	University of North Carolina, Chapel Hill

More Information

Additional Information:

University of North Carolina website This link exits the ClinicalTrials.gov site

Publications:

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World Health Organization. (2013). Global tuberculosis report 2013. Geneva: WHO.

Millen SJ, Uys PW, Hargrove J, van Helden PD, Williams BG. The effect of diagnostic delays on the drop-out rate and the total delay to diagnosis of tuberculosis. PLoS One. 2008 Apr 9;3(4):e1933. doi: 10.1371/journal.pone.0001933.

Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, Milovic A, Jones M, O'Brien SM, Persing DH, Ruesch-Gerdes S, Gotuzzo E, Rodrigues C, Alland D, Perkins MD. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010 Sep 9;363(11):1005-15. doi: 10.1056/NEJMoa0907847. Epub 2010 Sep 1.

Boehme CC, Nicol MP, Nabeta P, Michael JS, Gotuzzo E, Tahirli R, Gler MT, Blakemore R, Worodria W, Gray C, Huang L, Caceres T, Mehdiyev R, Raymond L, Whitelaw A, Sagadevan K, Alexander H, Albert H, Cobelens F, Cox H, Alland D, Perkins MD. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet. 2011 Apr 30;377(9776):1495-505. doi: 10.1016/S0140-6736(11)60438-8. Epub 2011 Apr 18.

Lawn SD, Brooks SV, Kranzer K, Nicol MP, Whitelaw A, Vogt M, Bekker LG, Wood R. Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay: a prospective study. PLoS Med. 2011 Jul;8(7):e1001067. doi: 10.1371/journal.pmed.1001067. Epub 2011 Jul 26.

Boehme, C. C. Oral Presentation, 20th Conference on Retroviruses and Opportunistic Infections. Georgia World Conference Centre, Atlanta, USA, March 3-6, 2013.

Theron G, Zijenah L, Chanda D, Clowes P, Rachow A, Lesosky M, Bara W, Mungofa S, Pai M, Hoelscher M, Dowdy D, Pym A, Mwaba P, Mason P, Peter J, Dheda K; TB-NEAT team. Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial. Lancet. 2014 Feb 1;383(9915):424-35. doi: 10.1016/S0140-6736(13)62073-5. Epub 2013 Oct 28.

Office of the U.S. Global AIDS Coordinator. Scaling Up TB Prevention, Screening, Diagnosis and Care in Zambia: Implementing the WHO 3I's, Program Protocol. Lusaka: Centers for Disease Control and Prevention-Zambia, 2012.

Kivihya-Ndugga LE, van Cleeff MR, Githui WA, Nganga LW, Kibuga DK, Odhiambo JA, Klatser PR. A comprehensive comparison of Ziehl-Neelsen and fluorescence microscopy for the diagnosis of tuberculosis in a resource-poor urban setting. Int J Tuberc Lung Dis. 2003 Dec;7(12):1163-71.

UNAIDS. Global Report: UNAIDS report on the global AIDS epidemic 2013. Geneva: Joint United Nations Programme on HIV/AIDS, 2013.

Getahun H, Harrington M, O'Brien R, Nunn P. Diagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes. Lancet. 2007 Jun 16;369(9578):2042-2049. doi: 10.1016/S0140-6736(07)60284-0.

Steingart KR, Henry M, Ng V, Hopewell PC, Ramsay A, Cunningham J, Urbanczik R, Perkins M, Aziz MA, Pai M. Fluorescence versus conventional sputum smear microscopy for tuberculosis: a systematic review. Lancet Infect Dis. 2006 Sep;6(9):570-81. doi: 10.1016/S1473-3099(06)70578-3. Erratum In: Lancet Infect Dis. 2006 Oct;6(10):628.

Sreeramareddy CT, Panduru KV, Menten J, Van den Ende J. Time delays in diagnosis of pulmonary tuberculosis: a systematic review of literature. BMC Infect Dis. 2009 Jun 11;9:91. doi: 10.1186/1471-2334-9-91.

Cohen T, Murray M, Wallengren K, Alvarez GG, Samuel EY, Wilson D. The prevalence and drug sensitivity of tuberculosis among patients dying in hospital in KwaZulu-Natal, South Africa: a postmortem study. PLoS Med. 2010 Jun 22;7(6):e1000296. doi: 10.1371/journal.pmed.1000296.

Vassall A, van Kampen S, Sohn H, Michael JS, John KR, den Boon S, Davis JL, Whitelaw A, Nicol MP, Gler MT, Khaliqov A, Zamudio C, Perkins MD, Boehme CC, Cobelens F. Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis. PLoS Med. 2011 Nov;8(11):e1001120. doi: 10.1371/journal.pmed.1001120. Epub 2011 Nov 8.

Steingart KR, Sohn H, Schiller I, Kloda LA, Boehme CC, Pai M, Dendukuri N. Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD009593. doi: 10.1002/14651858.CD009593.pub2.

Dowdy DW, Davis JL, den Boon S, Walter ND, Katamba A, Cattamanchi A. Population-level impact of same-day microscopy and Xpert MTB/RIF for tuberculosis diagnosis in Africa. PLoS One. 2013 Aug 12;8(8):e70485. doi: 10.1371/journal.pone.0070485. eCollection 2013.

Van Rie A, Page-Shipp L, Hanrahan CF, Schnippel K, Dansey H, Bassett J, Clouse K, Scott L, Stevens W, Sanne I. Point-of-care Xpert(R) MTB/RIF for smear-negative tuberculosis suspects at a primary care clinic in South Africa. Int J Tuberc Lung Dis. 2013 Mar;17(3):368-72. doi: 10.5588/ijtld.12.0392.

Hanrahan CF, Selibas K, Deery CB, Dansey H, Clouse K, Bassett J, Scott L, Stevens W, Sanne I, Van Rie A. Time to treatment and patient outcomes among TB suspects screened by a single point-of-care xpert MTB/RIF at a primary care clinic in Johannesburg, South Africa. PLoS One. 2013 Jun 6;8(6):e65421. doi: 10.1371/journal.pone.0065421. Print 2013.

Clouse K, Page-Shipp L, Dansey H, Moatlhodi B, Scott L, Bassett J, Stevens W, Sanne I, Van Rie A. Implementation of Xpert MTB/RIF for routine point-of-care diagnosis of tuberculosis at the primary care level. S Afr Med J. 2012 Sep 7;102(10):805-7. doi: 10.7196/samj.5851.

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Henostroza G, Harris J, Siyambango M, et al. High prevalence of tuberculosis among new HIV care enrolees in Zambia: urgent need for an enhanced screening approach. Oral presentation, 43rd World Conference on Lung Health. Kuala Lumpur Convention Centre, Kuala Lumpur, Malaysia. November 13 - 17, 2012.

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Chang K, Lu W, Wang J, Zhang K, Jia S, Li F, Deng S, Chen M. Rapid and effective diagnosis of tuberculosis and rifampicin resistance with Xpert MTB/RIF assay: a meta-analysis. J Infect. 2012 Jun;64(6):580-8. doi: 10.1016/j.jinf.2012.02.012. Epub 2012 Feb 27.

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Responsible Party:	University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:	NCT02729532
Other Study ID Numbers:	14-1697 US NIH Grant P30 AI50410-17 ( Other Grant/Funding Number: US NIH )
First Posted:	April 6, 2016 Key Record Dates
Last Update Posted:	April 22, 2019
Last Verified:	April 2019

Keywords provided by University of North Carolina, Chapel Hill:


Extra-pulmonary tuberculosis multiple drug resistant tuberculosis mycobacterium tuberculosis human immunodeficiency virus

Additional relevant MeSH terms:

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Tuberculosis Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections	Bacterial Infections Bacterial Infections and Mycoses Infections

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