Optimizing Clinical Outcomes in HIV-Infected Adults & Children

NCT02043080 | Completed

• 1 other identifier: 12-1402
• Study Type: interventional
• Target: 1,436
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study to evaluate Xpert MTB/RIF as the first-line TB diagnostic test in HIV-infected adults and pediatric patients as a means to obtain faster, more accurate TB diagnosis.

Conditions

Tuberculosis Diagnosis; HIV

Keywords

Tuberculosis; HIV; Xpert MTB/RIF; Determine TB-LAM; UNC; Zambia; Cost Effectiveness Analysis Curve; Centre for Infectious Disease Research in Zambia

Outcome Measures

Primary Outcomes (1)

• Proportions of adult and paediatric patients receiving appropriate TB treatment in each study phase

  proportions of adult and pediatric patients receiving appropriate TB treatment in each study phase, using mycobacterial culture as the reference standard, and the feasibility and cost effectiveness of Xpert MTB/RIF in this setting

  within 4 weeks of initiation

Secondary Outcomes (1)

• Clinical outcomes of subjects screened using the Xpert MTB/RIF algorithm compared to existing standard of care.

  3 and 6 months post TB-screening

Other Outcomes (1)

• Diagnostic performance of Xpert MTB/RIF

  screening visit, 3 and 6 months post screening

Study Arms (2)

SOC: sputum smear and Chest x-ray

NO INTERVENTION

HIV-infected adult and pediatric TB suspects screened for TB according to current standard of care

Xpert MTB/RIF, sputum, chest xray &TB culture

EXPERIMENTAL

HIV-infected adult and pediatric TB suspects screened for TB using the Xpert MTB/RIF Tuberculosis diagnostic tool (algorithm) which include chest x-ray, sputum TB culture

Other: Xpert MTB/RIF Tuberculosis diagnostic tool

Interventions

Xpert MTB/RIF Tuberculosis diagnostic tool OTHER

This is s new diagnostic tool that has been approved by WHO for the diagnosis of TB in HIV-infected patients in resource limited settings

Also known as: Gene Xpert MTB RIF (Cepheid Inc)

Xpert MTB/RIF, sputum, chest xray &TB culture

Eligibility Criteria

• Age: Up to 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 15 years or above ("Adult"), or less than 15 years old ("Child") ;
• HIV-infected and enrolled in HIV care at Chongwe and Kafue District Hospitals
• Intends to continue receiving care at the district hospital for at least 6 months.
• TB suspects according to Zambian National Guidelines \[31\] ;
• Willing to provide signed informed consent (or parental consent, if the participant is under 18);
• Willing (or parent or guardian willing) to provide locator information and allow contact by phone or home visit

You may not qualify if:

• Diagnosed with TB within the last 6 months or taken TB treatment in the last 3 months
• Enrolled in another study which might interfere with study objectives (ex. TB-HAART)

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Centre for Infectious Disease Research in Zambia

Lusaka, Zambia

Location

Related Publications (38)

• World Health Organization, Global Tuberculosis Control: WHO Report 2011. 2011:Geneva, Switzerland.

  BACKGROUND

• Ayles H, Schaap A, Nota A, Sismanidis C, Tembwe R, De Haas P, Muyoyeta M, Beyers N; Peter Godfrey-Faussett for the ZAMSTAR Study Team. Prevalence of tuberculosis, HIV and respiratory symptoms in two Zambian communities: implications for tuberculosis control in the era of HIV. PLoS One. 2009;4(5):e5602. doi: 10.1371/journal.pone.0005602. Epub 2009 May 19.

  PMID: 19440346 BACKGROUND

• Reid, S.E., Unpublished Data: Enhanced TB Screening to determine the prevalence and incidence of TB in a cohort of HIV clinic patients in Lusaka, Zambia. 2012.

  BACKGROUND

• Lawn SD, Harries AD, Anglaret X, Myer L, Wood R. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS. 2008 Oct 1;22(15):1897-908. doi: 10.1097/QAD.0b013e32830007cd.

  PMID: 18784453 BACKGROUND

• Lawn SD, Kranzer K, Wood R. Antiretroviral therapy for control of the HIV-associated tuberculosis epidemic in resource-limited settings. Clin Chest Med. 2009 Dec;30(4):685-99, viii. doi: 10.1016/j.ccm.2009.08.010.

  PMID: 19925961 BACKGROUND

• Henostroza, G., Unpublished work: Enhancing TB Screening in Zambian Prisons. 2011.

  BACKGROUND

• Reid MJ, Shah NS. Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings. Lancet Infect Dis. 2009 Mar;9(3):173-84. doi: 10.1016/S1473-3099(09)70043-X.

  PMID: 19246021 BACKGROUND

• Dawson R, Masuka P, Edwards DJ, Bateman ED, Bekker LG, Wood R, Lawn SD. Chest radiograph reading and recording system: evaluation for tuberculosis screening in patients with advanced HIV. Int J Tuberc Lung Dis. 2010 Jan;14(1):52-8.

  PMID: 20003695 BACKGROUND

• Walls T, Shingadia D. Global epidemiology of paediatric tuberculosis. J Infect. 2004 Jan;48(1):13-22. doi: 10.1016/s0163-4453(03)00121-x.

  PMID: 14667788 BACKGROUND

• Hesseling AC, Cotton MF, Jennings T, Whitelaw A, Johnson LF, Eley B, Roux P, Godfrey-Faussett P, Schaaf HS. High incidence of tuberculosis among HIV-infected infants: evidence from a South African population-based study highlights the need for improved tuberculosis control strategies. Clin Infect Dis. 2009 Jan 1;48(1):108-14. doi: 10.1086/595012.

  PMID: 19049436 BACKGROUND

• Lawn SD. Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review. BMC Infect Dis. 2012 Apr 26;12:103. doi: 10.1186/1471-2334-12-103.

  PMID: 22536883 BACKGROUND

• Lusaka Urban District Health Management Team, Annual Tuberculosis Report. 2009.

  BACKGROUND

• Turnbull ER, Kaunda K, Harris JB, Kapata N, Muvwimi MW, Kruuner A, Henostroza G, Reid SE. An evaluation of the performance and acceptability of three LED fluorescent microscopes in Zambia: lessons learnt for scale-up. PLoS One. 2011;6(11):e27125. doi: 10.1371/journal.pone.0027125. Epub 2011 Nov 4.

  PMID: 22073271 BACKGROUND

• Kang'ombe CT, Harries AD, Ito K, Clark T, Nyirenda TE, Aldis W, Nunn PP, Semba RD, Salaniponi FM. Long-term outcome in patients registered with tuberculosis in Zomba, Malawi: mortality at 7 years according to initial HIV status and type of TB. Int J Tuberc Lung Dis. 2004 Jul;8(7):829-36.

  PMID: 15260273 BACKGROUND

• Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, Gengiah T, Nair G, Bamber S, Singh A, Khan M, Pienaar J, El-Sadr W, Friedland G, Abdool Karim Q. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010 Feb 25;362(8):697-706. doi: 10.1056/NEJMoa0905848.

  PMID: 20181971 BACKGROUND

• Blanc, F.-X., et al., Early (2 weeks) vs. late (8 weeks) initiation of highly active antiretroviral treatment (HAART) significantly enhance survival of severely immunosuppressed HIV-infected adults with newly diagnosed tuberculosis: results of the CAMELIA clinical trial. BMC Proceedings, 2011. 5(Suppl 1): p. O11.

  BACKGROUND

• Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, Luetkemeyer AF, Hogg E, Rooney JF, Wu X, Hosseinipour MC, Lalloo U, Veloso VG, Some FF, Kumarasamy N, Padayatchi N, Santos BR, Reid S, Hakim J, Mohapi L, Mugyenyi P, Sanchez J, Lama JR, Pape JW, Sanchez A, Asmelash A, Moko E, Sawe F, Andersen J, Sanne I; AIDS Clinical Trials Group Study A5221. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1482-91. doi: 10.1056/NEJMoa1013607.

  PMID: 22010914 BACKGROUND

• Nicol MP, Zar HJ. New specimens and laboratory diagnostics for childhood pulmonary TB: progress and prospects. Paediatr Respir Rev. 2011 Mar;12(1):16-21. doi: 10.1016/j.prrv.2010.09.008. Epub 2010 Oct 16.

  PMID: 21172670 BACKGROUND

• Osborne CM. The challenge of diagnosing childhood tuberculosis in a developing country. Arch Dis Child. 1995 Apr;72(4):369-74. doi: 10.1136/adc.72.4.369. No abstract available.

  PMID: 7763076 BACKGROUND

• Chintu C, Mudenda V, Lucas S, Nunn A, Lishimpi K, Maswahu D, Kasolo F, Mwaba P, Bhat G, Terunuma H, Zumla A; UNZA-UCLMS Project Paediatric Post-mortem Study Group. Lung diseases at necropsy in African children dying from respiratory illnesses: a descriptive necropsy study. Lancet. 2002 Sep 28;360(9338):985-90. doi: 10.1016/S0140-6736(02)11082-8.

  PMID: 12383668 BACKGROUND

• World Health Organization, Roadmap for rolling out Xpert MTB/RIF for rapid diagnosis of TB and MDR-TB. 2010.

  BACKGROUND

• 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.

  PMID: 20825313 BACKGROUND

• Hillemann D, Rusch-Gerdes S, Boehme C, Richter E. Rapid molecular detection of extrapulmonary tuberculosis by the automated GeneXpert MTB/RIF system. J Clin Microbiol. 2011 Apr;49(4):1202-5. doi: 10.1128/JCM.02268-10. Epub 2011 Jan 26.

  PMID: 21270230 BACKGROUND

• Nicol MP, Workman L, Isaacs W, Munro J, Black F, Eley B, Boehme CC, Zemanay W, Zar HJ. Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study. Lancet Infect Dis. 2011 Nov;11(11):819-24. doi: 10.1016/S1473-3099(11)70167-0. Epub 2011 Jul 19.

  PMID: 21764384 BACKGROUND

• Policy Statement: Automated Real-Time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF System. Geneva: World Health Organization; 2011. Available from http://www.ncbi.nlm.nih.gov/books/NBK304235/

  PMID: 26158191 BACKGROUND

• 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.

  PMID: 21507477 BACKGROUND

• Marlowe EM, Novak-Weekley SM, Cumpio J, Sharp SE, Momeny MA, Babst A, Carlson JS, Kawamura M, Pandori M. Evaluation of the Cepheid Xpert MTB/RIF assay for direct detection of Mycobacterium tuberculosis complex in respiratory specimens. J Clin Microbiol. 2011 Apr;49(4):1621-3. doi: 10.1128/JCM.02214-10. Epub 2011 Feb 2.

  PMID: 21289151 BACKGROUND

• Theron G, Peter J, van Zyl-Smit R, Mishra H, Streicher E, Murray S, Dawson R, Whitelaw A, Hoelscher M, Sharma S, Pai M, Warren R, Dheda K. Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting. Am J Respir Crit Care Med. 2011 Jul 1;184(1):132-40. doi: 10.1164/rccm.201101-0056OC. Epub 2011 Apr 14.

  PMID: 21493734 BACKGROUND

• Lawn SD, Little F, Bekker LG, Kaplan R, Campbel E, Orrell C, Wood R. Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa. AIDS. 2009 Jan 28;23(3):335-42. doi: 10.1097/QAD.0b013e328321823f.

  PMID: 19114870 BACKGROUND

• Badri M, Wilson D, Wood R. Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study. Lancet. 2002 Jun 15;359(9323):2059-64. doi: 10.1016/S0140-6736(02)08904-3.

  PMID: 12086758 BACKGROUND

• Zambia Ministry of Health National Tuberculosis and Leprosy Control Programme, Tuberculosis and TB/HIV Manual. 2008: Lusaka.

  BACKGROUND

• World Health Organization, Rapid Implementation of the Xpert MTB/RIF diagnostic test: Technical and operational 'How-to' Practical considerations. 2011.

  BACKGROUND

• Francis J. Curry National Tuberculosis Center Institutional Consultation Services, Conducting Sputum Induction Safely. 1999.

  BACKGROUND

• World Health Organization, Guidelines for cost and cost-effectivness analysis of tuberculosis control. 2002.

  BACKGROUND

• Petitti, D., Meta-Analysis, Decision Analysis, and Cost-Effectivness Analysis. Methods for Quantitative Synthesis in Medicine. 2nd edition ed. 2000, New York: Oxford Press.

  BACKGROUND

• Drummond MF, S., M.J., Torrance, G.W., O'Brien, B.J., Stoddart, G.L., Methods for the Economic Evaluation of Health Car Programmes. Vol. 3rd edition. 2005: Oxford University Press.

  BACKGROUND

• Craig BA, Black MA. Incremental cost-effectiveness ratio and incremental net-health benefit: two sides of the same coin. Expert Rev Pharmacoecon Outcomes Res. 2001 Oct;1(1):37-46. doi: 10.1586/14737167.1.1.37.

  PMID: 19807506 BACKGROUND

• Hoch JS, Rockx MA, Krahn AD. Using the net benefit regression framework to construct cost-effectiveness acceptability curves: an example using data from a trial of external loop recorders versus Holter monitoring for ambulatory monitoring of "community acquired" syncope. BMC Health Serv Res. 2006 Jun 6;6:68. doi: 10.1186/1472-6963-6-68.

  PMID: 16756680 BACKGROUND

Related Links

• University of North Carolina website

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Stewart Reid, MD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

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 16, 2014
• First Posted: January 23, 2014
• Study Start: August 1, 2012
• Primary Completion: March 1, 2016
• Study Completion: April 1, 2017
• Last Updated: August 3, 2017

Record last verified: 2017-05

Locations

ZA (1)