Xpert MTB/RIF Test in the Diagnosis of Pulmonary Tuberculosis

NCT ID: NCT04433195

Last Updated: 2022-05-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

6900 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-15

Study Completion Date

2022-12-31

Brief Summary

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Currently in Taiwan, most clinicians use sputum smear and culture for the diagnosis of pulmonary tuberculosis (TB) and apply nucleic acid amplification (NAA) test in a selected manner. In 2013, the World Health Organization issued conditional recommendation that Xpert MTB/RIF may be used rather than conventional microscopy and culture as the initial diagnostic test in all adults suspected of having TB. The newly published Taiwan guidelines for TB diagnosis and treatment has recommended NAA test, together with smear and culture, as the initial diagnostic test in individuals suspected of having TB. The investigators conduct a prospective study to investigate the use of Xpert MTB/RIF as the initial diagnostic test of pulmonary TB under a pragmatic trial design.

Detailed Description

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In this study the investigators will respect current practice in the use of NAA in the diagnosis of pulmonary TB. Clinicians may have ordered NAA as the initial diagnostic test in adults suspected of having pulmonary TB (group A, Immediate NAA by clinician), and the investigators will not intervene. For patients who do not have NAA as the initial diagnostic test, the investigators will use random permuted blocks to randomize these participants into two groups. One group will have immediate Xpert test (intervention group) as the initial diagnostic test and another group will continue usual care without immediate Xpert test (control group).

Group A (Immediate NAA by clinician): NAA as the initial diagnostic test for pulmonary TB requested by clinicians.

Group B (Immediate NAA as intervention): NAA as the initial diagnostic test for pulmonary TB not requested by clinicians, but is performed as intervention in this study (intervention group).

Group C (No immediate NAA): NAA as the initial diagnostic test for pulmonary TB not requested by clinicians, and is not performed as the initial diagnostic test in this study (control group). NAA may be ordered at a later point in time by clinicians as an add-on test after sputum smear microscopy.

The investigators will assess pulmonary TB cases detected in all groups regarding

1. The interval between sputum examinations and initiation of ant-TB treatment.
2. The proportion of culture confirmed pulmonary TB among all pulmonary TB cases notified.
3. The proportion of TB patients who are advised to stop anti-TB treatment before completion of a treatment course.
4. Outcome of tuberculosis treatment, including patients who die before anti-TB treatment.

Among patients with NAA as the initial diagnostic test (Group A and Group B), the investigators will investigate

1. Performance (sensitivity, specificity and predictive values) of NAA in the diagnosis of culture positive pulmonary TB.
2. The incremental yield of the second and third smear in patients who have both NAA test and smear microscopy as the initial diagnostic test, aiming to determine the contribution of the second and third smear in the diagnosis of pulmonary TB.
3. The proportion of NAA positive cases who were culture negative.

Conditions

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Pulmonary Tuberculosis Confirmation by Culture

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

pragmatic trial
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

both care providers and participants will be informed of positive results of Xpert MTB/RIF test

Study Groups

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Immediate NAA by clinician

Nucleic acid amplification test requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB

Group Type ACTIVE_COMPARATOR

Xpert MTB/RIF test

Intervention Type DIAGNOSTIC_TEST

Xpert MTB/RIF performed as the initial diagnostic test for the diagnosis of pulmonary TB

Immediate NAA as intervention

Nucleic acid amplification test not requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB, but Xpert MTB/RIF is performed as intervention in this study (intervention group)

Group Type EXPERIMENTAL

Xpert MTB/RIF test

Intervention Type DIAGNOSTIC_TEST

Xpert MTB/RIF performed as the initial diagnostic test for the diagnosis of pulmonary TB

No immediate NAA

Nucleic acid amplification test not requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB, and Xpert MTB/RIF is not performed as the initial diagnostic test in this study (control group). Nucleic acid amplification test may be ordered at a later point in time by clinicians as an add-on test after sputum smear microscopy

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Xpert MTB/RIF test

Xpert MTB/RIF performed as the initial diagnostic test for the diagnosis of pulmonary TB

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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nucleic acid amplification test

Eligibility Criteria

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Inclusion Criteria

* All presumptive tuberculosis cases who have sputum examinations for the diagnosis of pulmonary TB

Exclusion Criteria

* Tuberculosis cases who have been on treatment for 14 or more days who have sputum examinations for follow-up
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Buddhist Tzu Chi General Hospital

OTHER

Sponsor Role collaborator

Chest Hospital, Ministry of Health and Welfare, Taiwan

OTHER_GOV

Sponsor Role collaborator

Chang-Hua Hospital

OTHER_GOV

Sponsor Role collaborator

Taichung Veterans General Hospital

OTHER

Sponsor Role collaborator

Taipei Medical University WanFang Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chen-Yuan Chiang, MD,DrPhilos

Role: PRINCIPAL_INVESTIGATOR

Wan Fang Hospital, Taipei Medical University, Taiwan

Locations

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Chang-Hua Hospital

Chang-hua, , Taiwan

Site Status

Buddhist Tzu Chi General Hospital

Hualien City, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

Chest Hospital, Ministry of Health and Welfare

Tainan City, , Taiwan

Site Status

Wan Fang Hospital, Taipei Medical University

Taipei, , Taiwan

Site Status

Countries

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Taiwan

References

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Chiang CY, Enarson DA, Bai KJ, Suo J, Wu YC, Lin TP, Luh KT. Factors associated with a clinician's decision to stop anti-tuberculosis treatment before completion. Int J Tuberc Lung Dis. 2008 Apr;12(4):441-6.

Reference Type RESULT
PMID: 18371272 (View on PubMed)

Chiang CY, Chang CT, Chang RE, Li CT, Huang RM. Patient and health system delays in the diagnosis and treatment of tuberculosis in Southern Taiwan. Int J Tuberc Lung Dis. 2005 Sep;9(9):1006-12.

Reference Type RESULT
PMID: 16158893 (View on PubMed)

Chen CC, Chiang CY, Pan SC, Wang JY, Lin HH. Health system delay among patients with tuberculosis in Taiwan: 2003-2010. BMC Infect Dis. 2015 Nov 2;15:491. doi: 10.1186/s12879-015-1228-x.

Reference Type RESULT
PMID: 26527404 (View on PubMed)

Pan SC, Chen YC, Wang JY, Sheng WH, Lin HH, Fang CT, Chang SC. Tuberculosis in Healthcare Workers: A Matched Cohort Study in Taiwan. PLoS One. 2015 Dec 17;10(12):e0145047. doi: 10.1371/journal.pone.0145047. eCollection 2015.

Reference Type RESULT
PMID: 26679188 (View on PubMed)

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.

Reference Type RESULT
PMID: 21507477 (View on PubMed)

Hermans S, Caldwell J, Kaplan R, Cobelens F, Wood R. The impact of the roll-out of rapid molecular diagnostic testing for tuberculosis on empirical treatment in Cape Town, South Africa. Bull World Health Organ. 2017 Aug 1;95(8):554-563. doi: 10.2471/BLT.16.185314. Epub 2017 Apr 28.

Reference Type RESULT
PMID: 28804167 (View on PubMed)

Cox H, Dickson-Hall L, Ndjeka N, Van't Hoog A, Grant A, Cobelens F, Stevens W, Nicol M. Delays and loss to follow-up before treatment of drug-resistant tuberculosis following implementation of Xpert MTB/RIF in South Africa: A retrospective cohort study. PLoS Med. 2017 Feb 21;14(2):e1002238. doi: 10.1371/journal.pmed.1002238. eCollection 2017 Feb.

Reference Type RESULT
PMID: 28222095 (View on PubMed)

Cox HS, Mbhele S, Mohess N, Whitelaw A, Muller O, Zemanay W, Little F, Azevedo V, Simpson J, Boehme CC, Nicol MP. Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: a pragmatic randomised trial. PLoS Med. 2014 Nov 25;11(11):e1001760. doi: 10.1371/journal.pmed.1001760. eCollection 2014 Nov.

Reference Type RESULT
PMID: 25423041 (View on PubMed)

Naidoo P, Dunbar R, Lombard C, du Toit E, Caldwell J, Detjen A, Squire SB, Enarson DA, Beyers N. Comparing Tuberculosis Diagnostic Yield in Smear/Culture and Xpert(R) MTB/RIF-Based Algorithms Using a Non-Randomised Stepped-Wedge Design. PLoS One. 2016 Mar 1;11(3):e0150487. doi: 10.1371/journal.pone.0150487. eCollection 2016.

Reference Type RESULT
PMID: 26930400 (View on PubMed)

Calligaro GL, Zijenah LS, Peter JG, Theron G, Buser V, McNerney R, Bara W, Bandason T, Govender U, Tomasicchio M, Smith L, Mayosi BM, Dheda K. Effect of new tuberculosis diagnostic technologies on community-based intensified case finding: a multicentre randomised controlled trial. Lancet Infect Dis. 2017 Apr;17(4):441-450. doi: 10.1016/S1473-3099(16)30384-X. Epub 2017 Jan 5.

Reference Type RESULT
PMID: 28063795 (View on PubMed)

Mbonze NB, Tabala M, Wenzi LK, Bakoko B, Brouwer M, Creswell J, Van Rie A, Behets F, Yotebieng M. Xpert((R)) MTB/RIF for smear-negative presumptive TB: impact on case notification in DR Congo. Int J Tuberc Lung Dis. 2016 Feb;20(2):240-6. doi: 10.5588/ijtld.15.0177.

Reference Type RESULT
PMID: 26792478 (View on PubMed)

Automated Real-Time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF Assay for the Diagnosis of Pulmonary and Extrapulmonary TB in Adults and Children: Policy Update. Geneva: World Health Organization; 2013. Available from http://www.ncbi.nlm.nih.gov/books/NBK258608/

Reference Type RESULT
PMID: 25473701 (View on PubMed)

Lin HH, Dowdy D, Dye C, Murray M, Cohen T. The impact of new tuberculosis diagnostics on transmission: why context matters. Bull World Health Organ. 2012 Oct 1;90(10):739-747A. doi: 10.2471/BLT.11.101436. Epub 2012 Jul 16.

Reference Type RESULT
PMID: 23109741 (View on PubMed)

Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2014 Jan 21;2014(1):CD009593. doi: 10.1002/14651858.CD009593.pub3.

Reference Type RESULT
PMID: 24448973 (View on PubMed)

Mase SR, Ramsay A, Ng V, Henry M, Hopewell PC, Cunningham J, Urbanczik R, Perkins MD, Aziz MA, Pai M. Yield of serial sputum specimen examinations in the diagnosis of pulmonary tuberculosis: a systematic review. Int J Tuberc Lung Dis. 2007 May;11(5):485-95.

Reference Type RESULT
PMID: 17439669 (View on PubMed)

Lombardi G, Di Gregori V, Girometti N, Tadolini M, Bisognin F, Dal Monte P. Diagnosis of smear-negative tuberculosis is greatly improved by Xpert MTB/RIF. PLoS One. 2017 Apr 21;12(4):e0176186. doi: 10.1371/journal.pone.0176186. eCollection 2017.

Reference Type RESULT
PMID: 28430807 (View on PubMed)

Ford I, Norrie J. Pragmatic Trials. N Engl J Med. 2016 Aug 4;375(5):454-63. doi: 10.1056/NEJMra1510059. No abstract available.

Reference Type RESULT
PMID: 27518663 (View on PubMed)

Rieder HL, Chiang CY, Rusen ID. A method to determine the utility of the third diagnostic and the second follow-up sputum smear examinations to diagnose tuberculosis cases and failures. Int J Tuberc Lung Dis. 2005 Apr;9(4):384-91.

Reference Type RESULT
PMID: 15830743 (View on PubMed)

Other Identifiers

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N202002038

Identifier Type: -

Identifier Source: org_study_id

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