TB-CAPT CORE Truenat Trial

Molbio Truenat TB Platform Combined With the Truenat TB Assays for Detection of Tuberculosis and Rifampicin Resistance in Adults With Presumptive Pulmonary Tuberculosis at Primary-level Diagnostic Centres in Tanzania and Mozambique: a Pragmatic, Cluster-randomized Controlled Trial

A cluster randomized controlled trial to evaluate the effect of placing Truenat platform/TB assays at primary health care clinics combined with rapid communication of results on time to treatment initiation of microbiologically confirmed TB.

Study Overview

• Status: Active, not recruiting
• Conditions: Tuberculosis; Diagnoses Disease
• Intervention / Treatment: Diagnostic test: Truenat TB platform/TB assays

Detailed Description

A cluster randomized controlled trial to evaluate the effect of placing Truenat platform/TB assays at primary health care clinics combined with rapid communication of results on time to treatment initiation of microbiologically confirmed TB.

In a setup period (survey of study centers) before randomization, the healthcare facilities (=clinics) of 4 sites will be asked to provide information about the number of TB notifications per quarter covering the period 1/2018-6/2020. From this information the foreseeable number of examined patients ("size of a clinic") will be derived, which will be used as a strata variable in randomization process.

Facilities will be randomly allocated to the standard of care (control), or Truenat platform/TB assays (intervention).

A cluster refers to a clinic. The clusters will be assigned to intervention or control arm to one of two diagnostic procedures (SOC [smear microscopy and/or Xpert MTB/RIF Ultra off-site] vs Truenat platform/TB assays on-site) following a restricted randomization strategy, whereby 6 to 8 strata of clusters will be established using the stratification variables site (clinics belong to a site) and size and apply balance criteria for them. The number of strata per site depends on heterogeneity of the sizes of the clinics as established in setup period and may be increased, typically 1 or 2 strata per site will be established.

The primary endpoint will be compared in an individual level analysis with strata and intervention as fixed effects and cluster as random effect.

• Study Type: Interventional
• Enrollment (Estimated): 4200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Morten Ruhwald, MD, PhD; Phone Number: +41 22 710 05 91; Email: Morten.Ruhwald@finddx.org

Study Locations

• Mozambique
  • Maputo, Mozambique, 1100
    • Instituto Nacional de Saúde (INS)
  • Vila Da Manhiça
    • Manhiça, Vila Da Manhiça, Mozambique, 1929
      • Centro de Investigação em Saúde de Manhiça-Fundação
• Tanzania
  • Dar es Salaam, Tanzania, Box 78 373
    • Ifakara Health Institute
  • Mbeya, Tanzania, 2410
    • National Institute of Medical Research (NIMR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with presumptive pulmonary TB, as defined by the national TB treatment guidelines in each country: patients with cough more than 1-2 weeks and/or fever, night sweats, blood-stained sputum (haemoptysis) significant weight loss, abnormalities on chest radiograph
• Adults 18 years old and above who are able and willing to consent

Exclusion Criteria:

• Circumstances that raise doubt on free, informed consent (e.g. in a mentally impaired person or a prisoner)
• Already diagnosed with TB
• Currently receiving anti-TB therapy
• Patients with symptoms which are only attributable to extra-pulmonary TB
• Patients who are seriously ill and need to be admitted to hospital

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TB testing using the Truenat platform/TB assays; TB testing using the Truenat platform/TB assays placed at primary health care clinics combined with rapid communication of results and same day TB treatment initiation	Diagnostic test: Truenat TB platform/TB assays; Truenat TB platform/TB assays, a molecular diagnostic test developed by Molbio diagnostics, for the diagnosis of Mycobacterium tuberculosis complex (MTBC) and Truenat MTB-RIF Dx for detection of RIF resistance was endorsed in 2020 by the WHO for TB diagnosis. The system has been designed to be operated as a point-of-care- diagnostic solution in peripheral laboratories with minimal infrastructure. It takes about 25 minutes to do the DNA extraction and another 35 minutes to diagnose TB. It is portable and battery operated, have no need for a computer or laptop, and operate from 2-40 C ambient temperature. The system uses room temperature stable reagents with long shelf life.
No Intervention: Standard of care Arm; Standard of care for TB testing using a combination of smear microscopy and laboratory (off-site) Xpert testing, may vary by clinic depending on availability of transport and stock of Xpert MTB/RIF or Xpert MTB/RIF Ultra cartridges (Xpert).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with microbiological confirmation starting TB treatment within 7 days of their first visit among enrolled participants	Proportion of participants with microbiological confirmation starting TB treatment within 7 days of their first visit among enrolled participants	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to bacteriological confirmation of TB	Time to bacteriological confirmation of TB (up to 180 days) from enrolment	60 days
Proportion of patients treated for TB up to 60 days from enrolment	Proportion of patients treated for TB up to 60 days from enrolment	60 days
Proportion of participants with signs and symptoms suggestive of pulmonary TB starting TB treatment with microbiological confirmation within 60 days from enrolment	Proportion of participants with signs and symptoms suggestive of pulmonary TB starting TB treatment with microbiological confirmation within 60 days from enrolment	60 days
Cost and productivity related endpoints	Patients' costs related to care at 60 days from enrolment.; Number of lost working days over the past month at 60 days from enrolment; Monthly earning in the past month at 60 days from enrolment	60 days

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Collaborators: Ludwig-Maximilians - University of Munich; Ifakara Health Institute; Centro de Investigação em Saúde de Manhiça; Instituto Nacional de Saúde, Mozambique; National Institute for Medical Research, Tanzania
• Investigators: Principal Investigator: Katharina Kranzer, Medical Center of the University of Munich

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2022
• Primary Completion (Estimated): January 28, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): September 29, 2020

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: TB041-3/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual, de-identified participant data may be shared, including data dictionaries. Available documents include the study protocol and statistical analysis plan. Templates of the informed consent forms may be shared upon request. The data will be available immediately following publication with no end date, will be shared with anyone who wishes to access them, and will be available for any purpose of analyses.
• IPD Sharing Time Frame: Upon publication of the main study manuscript
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No