Chepetsa TB - Reducing TB Among HIV-Infected Malawians

This study is currently recruiting participants.
Verified March 2014 by Johns Hopkins University
Sponsor:
Information provided by (Responsible Party):
Dr. Richard Chaisson, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01450085
First received: October 7, 2011
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

The specific aims of this project are: (1) to compare the impact of using the routine screening and GeneXpert algorithms for TB case detection on Tuberculosis (TB)- and HIV-related outcomes; (2) to compare the impact of using the routine screening and GeneXpert algorithms for exclusion of TB prior to initiation of IPT and ART on TB- and HIV-related outcomes; and (3) to assess the relative cost-effectiveness of the routine screening and GeneXpert algorithms for TB case detection and exclusion of TB. The GeneXpert is a "disruptive technology"10 that could allow TB/HIV programs in resource-limited settings to leapfrog over solid and liquid culture-based TB diagnostic algorithms, and to remove a key barrier to scale up of ICF and IPT.


Condition Intervention Phase
Tuberculosis
Other: GeneXpert
Other: LED Microscopy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Impact of a New Molecular Tuberculosis (TB) Test on TB/HIV Outcomes Among HIV-

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Survival of newly-diagnosed HIV-infected patients at 1 year [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 2000
Study Start Date: September 2012
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: GeneXpert
Point of care GeneXpert
Other: GeneXpert
Point of care GeneXpert
Other: LED Microscopy
Point of care LED Microscopy
Active Comparator: LED Microscopy
Point of care LED Microscopy
Other: LED Microscopy
Point of care LED Microscopy

Detailed Description:

HIV and tuberculosis (TB) are, along with malaria, the leading infectious causes of death worldwide and in sub-Saharan Africa.1 In 2008, there were 2 million deaths from AIDS and 1.8 million deaths from TB worldwide.2, 3 The HIV epidemic has fueled an increase in the incidence of, prevalence of and mortality due to TB in the past 3 decades. 15% of TB cases are HIV co-infected worldwide.34 78% of HIV-infected TB cases are in Africa.3 TB is the leading cause of death and opportunistic infection among persons living with HIV/AIDS (PLWHA). The HIV epidemic has challenged time-tested TB control methods that are now failing in high HIV prevalence settings.5 The World Health Organization (WHO) has recommended that the Three I's - intensified case-finding for TB (ICF), isoniazid preventive therapy (IPT) and infection control for TB - be targeted at PLWHA.6 ICF and IPT have not been adequately implemented in part due to the absence of sensitive, specific and rapid TB tests. The Cepheid GeneXpert System, a new diagnostic test for TB, is a self-contained sputum-processing and real-time PCR system to detect the M. tuberculosis complex as well as rifampin resistance.78 The GeneXpert is rapid, highly sensitive and specific, can be used as a point-of-care test, and has low human resource, laboratory and infection control requirements.7, 8 The WHO Strategic and Advisory Group for TB has endorsed recommendations for widespread use of the GeneXpert.9 WHO strongly recommended that the GeneXpert should be used as the initial diagnostic test in HIV-infected TB suspects and multidrug-resistant TB (MDR-TB) suspects.9 WHO also recommended that implementation of the GeneXpert be phased in within the context of comprehensive national and MDR-TB strategic plans.9 WHO recognized that several operational conditions need to be met for successful implementation, including but not limited to stable electrical supply, security against theft, trained personnel and annual calibration of the instrument by a commercial supplier.9 WHO also noted that it is important to document the impact and cost-effectiveness of the GeneXpert for TB case detection.9

Trial Concept The overall objective of this proposal is to conduct a cluster-randomized trial of the relative impact and cost-effectiveness of a routine TB screening algorithm -- symptom screening and point-of-care LED fluorescence sputum smear microscopy - versus a GeneXpert-based TB screening algorithm - symptom screening and point-of-care GeneXpert testing - on reducing morbidity and mortality due to TB among HIV-infected Malawians. 12 public sector clinics in southern Malawi will be randomized to 1 of 2 algorithms for TB case detection as part of ICF and for exclusion of TB prior to IPT and antiretroviral therapy (ART) initiation. In the clinics assigned to the GeneXpert algorithm, newly diagnosed HIV-infected patients will be screened for symptoms of TB and, if symptomatic, will provide sputum for GeneXpert point-of-care TB testing. Under the routine screening algorithm, patients at a clinic will be screened for symptoms of TB and, if symptomatic, will provide sputum for point-of-care LED fluorescence smear microscopy. The current standard of care in Malawi and most of Africa is symptom screening and sputum smear microscopy using Ziehl-Neelsen stain (not LED fluorescence microscopy) alone. There is not sufficient evidence at this time to demonstrate whether point-of-care LED microscopy versus GeneXpert testing is likely to be superior with respect to clinical impact and/or cost-effectiveness. Outcomes will be measured at the clinic level.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All HIV-infected men and women > 18 years of age with newly diagnosed HIV at the 12 study clinics will be asked to participate in the study.

Exclusion Criteria:

  • Patients will be excluded from participation if they have a current diagnosis of TB and/or if they are currently taking IPT, TB treatment and/or ART.
  • Patients will also be excluded from participation if they cannot speak English or Chichewa;
  • if they have a language or hearing impairment; or
  • if they are prisoners.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01450085

Contacts
Contact: Richard Chaisson, MD 410.955.1755 rchaiss@jhmi.edu

Locations
Malawi
Recruiting
Blantyre, Thyolo District, Malawi
Recruiting
Blantyre, Malawi
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Elizabeth Corbett, MD Malawi Liverpool Wellcome Trust
Study Director: David Dowdy, MD. PhD Johns Hopkins Unviversity
Principal Investigator: Lawrence Moulton, PhD Johns Hopkins University
  More Information

No publications provided

Responsible Party: Dr. Richard Chaisson, Director, Center for Tuberculosis Research, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01450085     History of Changes
Other Study ID Numbers: 1R01AI093316 - 01A1
Study First Received: October 7, 2011
Last Updated: March 10, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on April 23, 2014