Hotspots, Households and Hospitals: Enhanced Drug-resistant Tuberculosis Case Finding in Namibia

Tuberculosis, Multidrug-Resistant Clinical Trial

— H3TB  

Official title:

Hotspots, Households and Hospitals: Enhanced Drug-resistant Tuberculosis Case Finding in Namibia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05022238
• Other study ID #: HGC/611/2021
• Status: Recruiting
• Start date: August 1, 2022
• Est. completion date: September 2026

Study information

• Verified date: February 2023
• Source: University of Namibia
• Contact: Mareli Claassens, PhD
• Phone: 264814482082
• Email: mclaassens[@]unam.na
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Poor case management, pharmacokinetic variability and on-going transmission have fostered the drug-resistant tuberculosis (DR-TB) epidemic leading to a global estimated number of >500,000 new multidrug resistant (MDR) TB cases per year, of which roughly 10% are extensively drug resistant (XDR). Namibia is a high TB burden country with an incidence rate of 446/100,000 in 2016; about 11,000 new cases per year. 3.9% of new cases and 8.7% of previously treated cases have MDR-TB. Whole genome sequencing (WGS) has recently been applied to interrogate the complete genetic code of Mycobacterium tuberculosis (Mtb) strains. WGS can be used to infer relationships between identified strains as well as determine genomic variations involved in resistance development.

The specific aims of the H3TB study are to: (i) characterise the DR-TB epidemic, in terms of clinical, epidemiological, geospatial, social network and laboratory data, to identify transmission hotspots in three regions of Namibia, (ii) evaluate the feasibility of targeted case finding intervention strategies to improve DR-TB control in highly affected populations and (iii) develop a transmission model to investigate the potential impact of the case finding intervention strategies on DR-TB incidence in Namibia.

A prospective surveillance study started in January 2020, which includes all DR-TB cases in Namibia, and which will nest H3TB. Data collection tools and other study implementation tools have been designed and implemented. The study team is working in close collaboration with the National Institute of Pathology, where all DR-TB cases from the country are registered, to ensure all possible cases are captured. This is important for the identification of transmission hotspots.

After HREC and MOHSS approval, individuals with GeneXpert® MTB/RIF rifampicin-resistant samples and a positive Mtb culture from three regions in Namibia will be included in a transmission hotspot identification study. Preliminary data have shown that DR-TB clusters exist in these regions. Clinical, epidemiological, geospatial, social network and laboratory data (GeneXpert® MTB/RIF, culture, drug sensitivity tests) will be collected. WGS capacity has been established at the UNAM research laboratory, where WGS will be performed on the samples of H3TB participants; results will be validated at the Research Center Borstel in Germany. These study results in conjunction with a systematic review and meta-analysis will inform the design of case finding interventions which will be evaluated through a mixed-methods feasibility study conducted at high transmission areas (hotspots, households and hospitals). Data from these studies and the TB programme will be used to develop the model which will include a health economics component.

The study will strengthen DR-TB diagnosis, surveillance and control, inform DR-TB case finding policy in Namibia and regionally, inform resource allocation by identifying high transmission areas and create preliminary data to design a large scale DR-TB case finding intervention.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2100
• Est. completion date: September 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• All cases diagnosed with drug-resistant TB in Namibia, in three regions of Khomas, Otjozondjupa and Ohangwena will be included for the first outcome. For the second outcome, all household members of DR-TB cases will be included; all hospital visitors to DR-TB cases will be included and community members at transmission hotspots will be included.

Exclusion Criteria:

• Anyone who does not give consent to participate.

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Multidrug-Resistant

Locations

Country	Name	City	State
Namibia	University of Namibia	Windhoek

Sponsors (9)

Lead Sponsor	Collaborator
University of Namibia	European and Developing Countries Clinical Trials Partnership (EDCTP), Imperial College London, Namibian National Tuberculosis and Leprosy Programme (NTLP), National Taiwan University, Research Center Borstel, UK Foreign, Commonwealth & Development Office (FCDO), UK Medical Research Council (MRC), University of Stellenbosch

Country where clinical trial is conducted

Namibia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of drug-resistant tuberculosis transmission hotspots in Namibia	Finding DR-TB transmission hotspots through whole genome sequencing (WGS), social network and shared space analyses, and geospatial analyses. WGS, social network and shared space data, and geospatial data, will be triangulated to identify transmission hotspots.	18 months
Primary	Feasibility study of three interventions to enhance drug-resistant TB case finding in Namibia, measured with a questionnaire	Evaluating the acceptability, yield and cost of three interventions, viz., finding cases in community transmission hotspots, in drug-resistant tuberculosis hospitals, and in households of drug-resistant tuberculosis patients, in three regions of Namibia	24 months
Primary	Transmission model	Using programmatic and data from outcomes 1 and 2 to develop and calibrate transmission model to look at the impact of scale-up of interventions	12 months