GeneXpert Performance Evaluation for Linkage to Tuberculosis Care

NCT03044158 | Completed Results DMC

• 2 other identifiers: R01HL130192PACTR201610001763265
• Study Type: interventional
• Target: 10,644
• Locations: 1 country
• Sites: 20

Brief Summary

The investigators' overall objective is to assess the effectiveness, implementation and costs of a streamlined TB diagnostic evaluation strategy based around rapid, onsite molecular testing. The intervention strategy was developed based on theory-informed assessment of barriers to TB diagnostic evaluation at community health centers in Uganda and a process of engagement with local stakeholders. It includes: 1) Point-of-care molecular testing using GeneXpert as a replacement for sputum smear microscopy; 2) Re-structuring of clinic-level procedures to facilitate same-day TB diagnosis and treatment; and 3) Quarterly feedback of TB evaluation metrics to health center staff. The investigators' central hypothesis is that the intervention strategy will have high uptake and increase the number of patients diagnosed with and treated for active pulmonary TB. To test this hypothesis, the investigators will conduct a pragmatic cluster-randomized trial at community health centers that provide TB microscopy services in Uganda in partnership with the National TB Program (NTP). The investigators utilize an effectiveness-implementation hybrid design in which, concurrent with the clinical trial, the investigators will conduct nested mixed methods, health economic and modeling studies to assess 1) whether the intervention strategy modifies targeted barriers to TB diagnostic evaluation; 2) fidelity of implementation of the intervention components (i.e, the degree to which intervention components were implemented as intended vs. adapted across sites); and 3) cost-effectiveness and public health impact.

Conditions

Tuberculosis, Pulmonary; Rifampicin Resistant Tuberculosis

Keywords

tuberculosis; implementation science; point-of-care; diagnostics; GeneXpert; Uganda

Outcome Measures

Primary Outcomes (1)

• Number Treated for Microbiologically-confirmed TB Within 14 Days After Presentation to the Health Center for TB Evaluation

  Effectiveness outcome.

  Within 14 days after presentation to the health center for tuberculosis evaluation

Secondary Outcomes (10)

• Number Diagnosed With Microbiologically-confirmed TB

  Within 14 days after presentation to the health center for tuberculosis evaluation

• Time to Microbiologically-confirmed TB

  Within 6 months of presentation to the health center for tuberculosis evaluation

• Number Treated for TB

  Within 14 days of presentation to the health center for tuberculosis evaluation

• Time-to-treatment of Microbiologically-confirmed TB

  Days from initial health center visit to initiation of treatment if diagnosed, up to 6 months.

• Number Who Died Within 6 Months

  Within 6 months of presentation to the health center for tuberculosis evaluation

Study Arms (2)

Control group

NO INTERVENTION

Onsite ZN or LED fluorescence microscopy + hub-based GeneXpert testing per existing protocols

Intervention

EXPERIMENTAL

Onsite molecular testing for TB with GeneXpert I + process redesign to facilitate same-day TB diagnosis and treatment + performance feedback

Device: GeneXpert I; Behavioral: Process re-design; Other: Performance Feedback

Interventions

GeneXpert I DEVICE

Onsite molecular testing with GeneXpert I as a replacement for microscopy

Also known as: GeneXpert

Intervention

Process re-design BEHAVIORAL

Research and Uganda NTLP staff will engage health center staff in a discussion of how to re-organize clinical, laboratory and pharmacy services to enable same-day TB diagnosis and treatment.

Intervention

Performance Feedback OTHER

Feedback of TB diagnostic evaluation quality indicators to health center staff

Intervention

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Site-level: Use standard (multi-day) sputum smear microscopy as the primary method of TB diagnosis
• Site-level: Participate in NTP-sponsored external quality assurance (EQA) for sputum smear microscopy
• Site-level: Send samples to a district or regional hospital/health center for Xpert testing
• Patient-level: Initiate evaluation for active TB at a study health center

You may not qualify if:

• Site-level: Do not agree to be randomized to standard-of-care vs. intervention arms
• Site-level: Perform sputum smear examination on \<150 patients per year (based on 2015 data)
• Site-level: Diagnose \<15 smear-positive TB cases per year (based on 2015 data)
• Patient-level: Have sputum collected for monitoring of response to anti-TB therapy
• Patient-level: Have sputum collected as part of active, community-based case finding (e.g., contact tracing, community outreach campaign)
• Patient-level: Referred to a study health center for TB treatment after a diagnosis is established elsewhere
• Patient-level: Started on TB treatment for extra-pulmonary TB only

Sponsors & Collaborators

• University of California, San Francisco: lead
• Makerere University: collaborator
• Johns Hopkins Bloomberg School of Public Health: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Yale University: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (20)

St Francis Njeru Health Center III

Buikwe, Uganda

Location

Busana Health Center III

Busana, Uganda

Location

Busesa Health Center IV

Busesa, Uganda

Location

Buwama Health Center III

Buwama, Uganda

Location

Iganga TC

Iganga, Uganda

Location

Bukulula Health Center IV

Kalungu, Uganda

Location

Nazigo Health Center III

Kayunga, Uganda

Location

Kiganda Health Center IV

Kiganda, Uganda

Location

Kira Health Center III

Kira, Uganda

Location

Lugasa Health Center III

Lugala, Uganda

Location

Bishop Asili Health Center

Luwero, Uganda

Location

Kinoni Health Center III

Lwengo, Uganda

Location

Kityerera Health Center IV

Mayuge, Uganda

Location

Malongo Health Center III

Mayuge, Uganda

Location

Mayuge Health Center III

Mayuge, Uganda

Location

Wabulungu Health Center III

Mayuge, Uganda

Location

Malangala Health Center III

Mityana, Uganda

Location

Lwampanga Health Center III

Nakasongola, Uganda

Location

Namungalwe Health Center III

Namungalwe, Uganda

Location

Nankandulo Health Center IV

Nankandulo, Uganda

Location

Related Publications (40)

• MacPherson P, Houben RM, Glynn JR, Corbett EL, Kranzer K. Pre-treatment loss to follow-up in tuberculosis patients in low- and lower-middle-income countries and high-burden countries: a systematic review and meta-analysis. Bull World Health Organ. 2014 Feb 1;92(2):126-38. doi: 10.2471/BLT.13.124800. Epub 2013 Nov 22.

  PMID: 24623906 BACKGROUND

• Cattamanchi A, Dowdy DW, Davis JL, Worodria W, Yoo S, Joloba M, Matovu J, Hopewell PC, Huang L. Sensitivity of direct versus concentrated sputum smear microscopy in HIV-infected patients suspected of having pulmonary tuberculosis. BMC Infect Dis. 2009 May 6;9:53. doi: 10.1186/1471-2334-9-53.

  PMID: 19419537 BACKGROUND

• Chihota VN, Ginindza S, McCarthy K, Grant AD, Churchyard G, Fielding K. Missed Opportunities for TB Investigation in Primary Care Clinics in South Africa: Experience from the XTEND Trial. PLoS One. 2015 Sep 18;10(9):e0138149. doi: 10.1371/journal.pone.0138149. eCollection 2015.

  PMID: 26383102 BACKGROUND

• Davis J, Katamba A, Vasquez J, Crawford E, Sserwanga A, Kakeeto S, Kizito F, Dorsey G, den Boon S, Vittinghoff E, Huang L, Adatu F, Kamya MR, Hopewell PC, Cattamanchi A. Evaluating tuberculosis case detection via real-time monitoring of tuberculosis diagnostic services. Am J Respir Crit Care Med. 2011 Aug 1;184(3):362-7. doi: 10.1164/rccm.201012-1984OC. Epub 2011 Mar 11.

  PMID: 21471088 BACKGROUND

• Aspler A, Menzies D, Oxlade O, Banda J, Mwenge L, Godfrey-Faussett P, Ayles H. Cost of tuberculosis diagnosis and treatment from the patient perspective in Lusaka, Zambia. Int J Tuberc Lung Dis. 2008 Aug;12(8):928-35.

  PMID: 18647453 BACKGROUND

• Kemp JR, Mann G, Simwaka BN, Salaniponi FM, Squire SB. Can Malawi's poor afford free tuberculosis services? Patient and household costs associated with a tuberculosis diagnosis in Lilongwe. Bull World Health Organ. 2007 Aug;85(8):580-5. doi: 10.2471/blt.06.033167.

  PMID: 17768515 BACKGROUND

• Simwaka BN, Bello G, Banda H, Chimzizi R, Squire BS, Theobald SJ. The Malawi National Tuberculosis Programme: an equity analysis. Int J Equity Health. 2007 Dec 31;6:24. doi: 10.1186/1475-9276-6-24.

  PMID: 18163918 BACKGROUND

• Botha E, den Boon S, Lawrence KA, Reuter H, Verver S, Lombard CJ, Dye C, Enarson DA, Beyers N. From suspect to patient: tuberculosis diagnosis and treatment initiation in health facilities in South Africa. Int J Tuberc Lung Dis. 2008 Aug;12(8):936-41.

  PMID: 18647454 BACKGROUND

• Ouyang H, Chepote F, Gilman RH, Moore DA. Failure to complete the TB diagnostic algorithm in urban Peru: a study of contributing factors. Trop Doct. 2005 Apr;35(2):120-1. doi: 10.1258/0049475054037002. No abstract available.

  PMID: 15970047 BACKGROUND

• 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.

  PMID: 24448973 BACKGROUND

• Dowdy DW, Cattamanchi A, Steingart KR, Pai M. Is scale-up worth it? Challenges in economic analysis of diagnostic tests for tuberculosis. PLoS Med. 2011 Jul;8(7):e1001063. doi: 10.1371/journal.pmed.1001063. Epub 2011 Jul 26.

  PMID: 21814496 BACKGROUND

• Keeler E, Perkins MD, Small P, Hanson C, Reed S, Cunningham J, Aledort JE, Hillborne L, Rafael ME, Girosi F, Dye C. Reducing the global burden of tuberculosis: the contribution of improved diagnostics. Nature. 2006 Nov 23;444 Suppl 1:49-57. doi: 10.1038/nature05446. No abstract available.

  PMID: 17159894 BACKGROUND

• 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.

  PMID: 24176144 BACKGROUND

• Glasgow RE, Vogt TM, Boles SM. Evaluating the public health impact of health promotion interventions: the RE-AIM framework. Am J Public Health. 1999 Sep;89(9):1322-7. doi: 10.2105/ajph.89.9.1322.

  PMID: 10474547 BACKGROUND

• Godin G, Belanger-Gravel A, Eccles M, Grimshaw J. Healthcare professionals' intentions and behaviours: a systematic review of studies based on social cognitive theories. Implement Sci. 2008 Jul 16;3:36. doi: 10.1186/1748-5908-3-36.

  PMID: 18631386 BACKGROUND

• Davis DA, Thomson MA, Oxman AD, Haynes RB. Evidence for the effectiveness of CME. A review of 50 randomized controlled trials. JAMA. 1992 Sep 2;268(9):1111-7.

  PMID: 1501333 BACKGROUND

• Cattamanchi A, Miller CR, Tapley A, Haguma P, Ochom E, Ackerman S, Davis JL, Katamba A, Handley MA. Health worker perspectives on barriers to delivery of routine tuberculosis diagnostic evaluation services in Uganda: a qualitative study to guide clinic-based interventions. BMC Health Serv Res. 2015 Jan 22;15:10. doi: 10.1186/s12913-014-0668-0.

  PMID: 25609495 BACKGROUND

• Ivers N, Jamtvedt G, Flottorp S, Young JM, Odgaard-Jensen J, French SD, O'Brien MA, Johansen M, Grimshaw J, Oxman AD. Audit and feedback: effects on professional practice and healthcare outcomes. Cochrane Database Syst Rev. 2012 Jun 13;2012(6):CD000259. doi: 10.1002/14651858.CD000259.pub3.

  PMID: 22696318 BACKGROUND

• Grogan S, Conner M, Norman P, Willits D, Porter I. Validation of a questionnaire measuring patient satisfaction with general practitioner services. Qual Health Care. 2000 Dec;9(4):210-5. doi: 10.1136/qhc.9.4.210.

  PMID: 11101705 BACKGROUND

• Nabbuye-Sekandi J, Makumbi FE, Kasangaki A, Kizza IB, Tugumisirize J, Nshimye E, Mbabali S, Peters DH. Patient satisfaction with services in outpatient clinics at Mulago hospital, Uganda. Int J Qual Health Care. 2011 Oct;23(5):516-23. doi: 10.1093/intqhc/mzr040. Epub 2011 Jul 19.

  PMID: 21775313 BACKGROUND

• Ivers NM, Halperin IJ, Barnsley J, Grimshaw JM, Shah BR, Tu K, Upshur R, Zwarenstein M. Allocation techniques for balance at baseline in cluster randomized trials: a methodological review. Trials. 2012 Aug 1;13:120. doi: 10.1186/1745-6215-13-120.

  PMID: 22853820 BACKGROUND

• Sismanidis C, Moulton LH, Ayles H, Fielding K, Schaap A, Beyers N, Bond G, Godfrey-Faussett P, Hayes R. Restricted randomization of ZAMSTAR: a 2 x 2 factorial cluster randomized trial. Clin Trials. 2008;5(4):316-27. doi: 10.1177/1740774508094747.

  PMID: 18697846 BACKGROUND

• Sandelowski M, Leeman J. Writing usable qualitative health research findings. Qual Health Res. 2012 Oct;22(10):1404-13. doi: 10.1177/1049732312450368. Epub 2012 Jun 28.

  PMID: 22745362 BACKGROUND

• Sandelowski MJ. Justifying qualitative research. Res Nurs Health. 2008 Jun;31(3):193-5. doi: 10.1002/nur.20272. No abstract available.

  PMID: 18288640 BACKGROUND

• Voils CI, Sandelowski M, Barroso J, Hasselblad V. Making Sense of Qualitative and Quantitative Findings in Mixed Research Synthesis Studies. Field methods. 2008;20(1):3-25. doi: 10.1177/1525822X07307463.

  PMID: 18677415 BACKGROUND

• Salje H, Andrews JR, Deo S, Satyanarayana S, Sun AY, Pai M, Dowdy DW. The importance of implementation strategy in scaling up Xpert MTB/RIF for diagnosis of tuberculosis in the Indian health-care system: a transmission model. PLoS Med. 2014 Jul 15;11(7):e1001674. doi: 10.1371/journal.pmed.1001674. eCollection 2014 Jul.

  PMID: 25025235 BACKGROUND

• Dowdy DW, Basu S, Andrews JR. Is passive diagnosis enough? The impact of subclinical disease on diagnostic strategies for tuberculosis. Am J Respir Crit Care Med. 2013 Mar 1;187(5):543-51. doi: 10.1164/rccm.201207-1217OC. Epub 2012 Dec 21.

  PMID: 23262515 BACKGROUND

• Sun AY, Denkinger CM, Dowdy DW. The impact of novel tests for tuberculosis depends on the diagnostic cascade. Eur Respir J. 2014 Nov;44(5):1366-9. doi: 10.1183/09031936.00111014. Epub 2014 Sep 3.

  PMID: 25186263 BACKGROUND

• Chandrasekaran V, Ramachandran R, Cunningham J, Balasubramaniun R, Thomas A, Sudha G, et al. Factors leading to tuberculosis diagnostic drop-out and delayed treatment initiation in Chennai, India. Int J Tuberc Lung Dis. 2005;9:172.

  BACKGROUND

• Den Boon S, Semitala F, Cattamanchi A, Walter N, Worodria W, Joloba M, Huang L, Davis JL. Impact of patient drop-out on the effective sensitivity of smear microscopy strategies. Am J Respir Crit Care Med 2010;181:A2258.

  BACKGROUND

• Miller C, Haguma P, Ochom E, Ross J, Davis JL, Cattamanchi A, Katamba A. Costs associated with tuberculosis evaluation in rural Uganda. 43rd Union World Conference on Lung Health; Kuala Lumpur, Malaysia 2012.

  BACKGROUND

• WHO. Global strategy and targets for tuberculosis prevention, care and control after 2015. Geneva, Switzerland: World Health Organization, 2013 EB134/12.

  BACKGROUND

• WHO. WHO monitoring of Xpert MTB/RIF roll-out. Available at: http://www.who.int/tb/areas-of-work/laboratory/mtb-rif-rollout/en/ [cited 2015 January 15].

  BACKGROUND

• Churchyard GJ, on behalf of the Xtend study team. Xpert MTB/RIF vs microscopy as the first line TB test in South Africa: mortality, yield, initial loss to follow up and proportion treated. The Xtend Study. Conference on Retroviruses and Opportunistic Infections; Boston, USA: Available at: http://www.stoptb.org/wg/gli/assets/documents/M6/Churchyard%20-%20XTEND%20study.pdf; 2014.

  BACKGROUND

• Cepheid. GeneXpert Omni: The True Point of Care Molecular Diagnostic System: Cepheid Inc; 2015. Available from: http://www.cepheid.com/us/genexpert-omni.

  BACKGROUND

• Ajzen I. The theory of planned behavior. Organizational Behavior and Human Decision Processes. 1991;50:179-211.

  BACKGROUND

• Green LW, Krueter M. Health Program Planning - An Educational and Ecological Approach. 4th ed. Philadelphia, USA: McGraw-Hill; 2005.

  BACKGROUND

• Hayes RJ, Moulton LH. Cluster Randomized Trials. Boca Raton, Florida, USA: CRC Press; 2009.

  BACKGROUND

• Cattamanchi A, Reza TF, Nalugwa T, Adams K, Nantale M, Oyuku D, Nabwire S, Babirye D, Turyahabwe S, Tucker A, Sohn H, Ferguson O, Thompson R, Shete PB, Handley MA, Ackerman S, Joloba M, Moore DAJ, Davis JL, Dowdy DW, Fielding K, Katamba A. Multicomponent Strategy with Decentralized Molecular Testing for Tuberculosis. N Engl J Med. 2021 Dec 23;385(26):2441-2450. doi: 10.1056/NEJMoa2105470.

  PMID: 34936740 DERIVED

• Reza TF, Nalugwa T, Farr K, Nantale M, Oyuku D, Nakaweesa A, Musinguzi J, Vangala M, Shete PB, Tucker A, Ferguson O, Fielding K, Sohn H, Dowdy D, Moore DAJ, Davis JL, Ackerman SL, Handley MA, Katamba A, Cattamanchi A. Study protocol: a cluster randomized trial to evaluate the effectiveness and implementation of onsite GeneXpert testing at community health centers in Uganda (XPEL-TB). Implement Sci. 2020 Apr 21;15(1):24. doi: 10.1186/s13012-020-00988-y.

  PMID: 32316993 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Adithya Cattamanchi
• Organization: University of California Irvine

Adithya.Cattamanchi@uci.edu

714-456-2959

Study Officials

• Adithya Cattamanchi, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2017
• First Posted: February 6, 2017
• Study Start: October 22, 2018
• Primary Completion: March 31, 2020
• Study Completion: July 31, 2022
• Last Updated: February 18, 2025
• Results First Posted: February 18, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

UG (20)