TB-CAPT EXULTANT - HIV

Expanding Xpert Ultra Testing for TB Diagnosis Among HIV-positive Patients Admitted to Hospital in Africa

The overall aim of this study is to assess the potential of an expanded TB testing strategy to increase the number of HIV-positive patients with microbiologically diagnosed TB who are started on treatment in adult wards of sub-Saharan Africa.

Study Overview

• Status: Recruiting
• Conditions: Tuberculosis; Diagnoses Disease; HIV Coinfection
• Intervention / Treatment: Diagnostic test: Concentrated urine with Xpert Ultra; Diagnostic test: Stool with Xpert Ultra

Detailed Description

To investigate the effect of an expanded TB screening strategy among HIV-positive patients admitted to hospital (including Ultra on sputum, stool and urine, and AlereLAM on urine, performed regardless of presence of TB symptoms) on the proportion of microbiologically-confirmed TB cases starting treatment within 72 hours of enrolment, compared to Ultra testing (on sputum/any tissue) and AlereLAM (on urine) in only those patients who are symptomatic for TB or fulfilling WHO testing recommendations.

to assess the impact of this screening strategy on 2-month all-cause mortality.

• to assess the feasibility of multiple specimens' collection for TB diagnosis within 72 hours of enrolment.

• Study Type: Interventional
• Enrollment (Estimated): 1172
• 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 Contact Backup: Name: Adam Penn-Nicholson, PhD; Phone Number: +41 22 710 05 91; Email: Adam.Penn-Nicholson@finddx.org

Study Locations

• Mozambique
  • Maputo, Mozambique, 1100
    • Recruiting
    • Instituto Nacional de Saúde (INS)
    • Contact: Celso Khosa, MD, PhD; Phone Number: +258 21431103; Email: celso.khosa@ins.gov.mz
  • Vila Da Manhiça
    • Manhiça, Vila Da Manhiça, Mozambique, 1929
      • Recruiting
      • Centro de Investigação em Saúde de Manhiça-Fundação
      • Contact: Dinis Nguenha, MD, MSC; Phone Number: +258 21 81 00 02/181; Email: dinis.nguenha@manhica.net
• Tanzania
  • Bagamoyo, Tanzania, 53502
    • Recruiting
    • Ifakara Health Institute (IHI)
    • Contact: Robert Ndege, MD, MSc; Phone Number: +255 23 233 3448; Email: rndege@ihi.or.tz
  • Mbeya, Tanzania, 2410
    • Recruiting
    • National Institute of Medical Research (NIMR)
    • Contact: Nyanda Ntinginya, MD, PhD; Phone Number: +255 25 2503364; Email: nelias@nimr-mmrc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults (18 years old and above)
2. Confirmed HIV infection by serology (including both antiretroviral (ART)- naïve and experienced)
3. Admitted to the hospital (adult medical wards) at the time of enrolment.

Exclusion Criteria:

1. Unable to provide informed consent (if no authorized relatives are in the position to provide the consent)
2. Living outside the catchment area of the participating hospital(s)
3. with plans to migrate outside the catchment area within 2 months after recruitment.
4. Currently receiving anti-TB therapy or having received anti TB therapy in the last 6 months prior to enrolment
5. Receiving preventive TB treatment in the preceding 6 months
6. Patients admitted for traumatic reasons, acute abdomen, delivery (maternal conditions), or for planned/scheduled surgery.
7. Referred from other hospital.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intervention arm; The intervention arm for this trial consists of HIV patients with TB testing performed regardless of presence of TB symptoms. Testing will be done on expectorated sputum, stool and concentrated urine with Ultra, and urine with AlereLAM. To fulfil exploratory objectives, we will also collect and store 2x tongue swabs for molecular TB diagnostic assay (Xpert Ultra and/or LumiraDx) testing, blood for testing with CRP, and urine samples which will be stored for retrospective FujiLAM testing and analysis.	Diagnostic test: Concentrated urine with Xpert Ultra; Molecular TB diagnostic test on urine; Diagnostic test: Stool with Xpert Ultra; Molecular TB diagnostic test on stool
No Intervention: control arm; The control arm for this trial will consist of patients managed according to the current WHO recommended TB testing practices for HIV positive inpatients (as of Q1 2020). TB testing will be done as follows: Sputum Ultra performed whenever the patient has cough, fever, weight loss over night sweats and/or Ultra performed on any tissue (including lymph nodes) from patients with clinical suspicion of extrapulmonary TB. and/or: Urine Alere TB-LAM performed if patients have signs and symptoms of TB (pulmonary and/or extrapulmonary), or with advanced HIV disease, or who are seriously ill, or else irrespective of signs and symptoms of TB, but combined with a CD4 cell count of less than 200 cells/mm .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of participants diagnosed with microbiologically confirmed TB and started on TB treatment within 72 hours of enrolment	The proportion of participants diagnosed with microbiologically confirmed TB and started on TB treatment within 72 hours of enrolment, separately for intervention and control arm. The numerator is the number of participants per study arm who are diagnosed with microbiologically confirmed TB and start on treatment within 72 hours of enrolment. The denominator is the number of participants enrolled per study arm. We will compare this indicator between both study arms.	72 hours after enrolment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eight-week all-cause mortality	Eight-week all-cause mortality (main secondary endpoint) among all participants enrolled. The numerator will be number of deaths during eight weeks after enrolment, the denominator is the number of participants enrolled. We will compare this indicator between both study arms.	8 weeks after enrolment
The proportion of participants who are diagnosed with TB (irrespective of bacteriological confirmation) and started TB treatment within 72 hours of enrolment.	The proportion of participants who are diagnosed with TB (irrespective of bacteriological confirmation) and started TB treatment within 72 hours of enrolment. The numerator is the number of participants diagnosed with TB (with or without bacteriological confirmation) who started treatment within 72 hours of enrolment; the denominator is the number of participants enrolled.	72 hours after enrolment

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Collaborators: Ludwig-Maximilians - University of Munich; Heidelberg University; Swiss Tropical & Public Health Institute; Ifakara Health Institute; Ospedale San Raffaele; Centro de Investigação em Saúde de Manhiça; Barcelona Institute for Global Health; Instituto Nacional de Saúde, Mozambique; National Institute for Medical Research, Tanzania; African Society for Laboratory Medicine
• Investigators: Principal Investigator: Alberto García-Basteiro, MD, Barcelona Institute for Global Health

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 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: Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Urogenital Diseases; Genital Diseases; HIV Infections; Disease; Tuberculosis; Coinfection
• Other Study ID Numbers: TB043-3/1

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: After publication of the primary peer-reviewed 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