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
Phase: NA
Conditions: Tuberculosis, Diagnoses Disease
Sponsor: Foundation for Innovative New Diagnostics, Switzerland

- CONFIDENTIAL - 
Page 1 of 57 
Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Trial Protocol 
 
 
Protocol Title:   
 
  
Molbio TruenatTM 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 
Short Title: 
TB-CAPT CORE Truenat trial 
Protocol Number:   TB041 -3/1-MOZ 
ClinicalTrials.gov:    NCT04568954 
 
 
 
 
 
 
Protocol Version 4.0 
 
 
18 January 2023 
 
 
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Page 2 of 57 
Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
Confidentiality Statement: 
 
The information contained in this document, especially unpublished data, is the property of FIND (or 
under its control) and may not be reproduced, published, or disclosed to others without prior written 
authorization from FIND. 
 
 
 
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Page 3 of 57 
Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
1. Table of contents 
CLINICAL STUDY PARTNERS ________________________________________________________________ 7 
SIGNATURE PAGE (SPONSOR) _________________________________________________________ 10 
CLINICAL TRIAL COORDINATOR _________________________________________________________ 10 
OTHER CLINICAL TRIAL PARTNERS _______________________________________________________ 10 
STATEMENT OF PRINCIPAL INVESTIGATOR _______________________________________________ 11 
1. 
ABBREVIATIONS / GLOSSARY OF TERMS _____________________________________________ 14 
2. 
PROTOCOL SYNOPSIS ____________________________________________________________ 15 
3. 
STUDY SCHEDULE OF EVENTS ______________________________________________________ 21 
4. 
SUMMARY OF THE PROPOSED RESEARCH IN LAY TERMS ________________________________ 22 
5. 
BACKGROUND INFORMATION _____________________________________________________ 24 
5.1 
TUBERCULOSIS EPIDEMIOLOGY ____________________________________________________ 24 
5.2 
LIMITED DIAGNOSTIC CAPACITY IN SUB-SAHARAN AFRICA __________________________________ 24 
FIGURE 1: TB DIAGNOSTIC PATHWAY ________________________________________________________ 25 
5.3 
GENEXPERT IMPLEMENTATION IN TANZANIA ___________________________________________ 26 
5.4 
GENEXPERT IMPLEMENTATION IN MOZAMBIQUE ________________________________________ 26 
FIGURE 2: GENEXPERT COVERAGE IN MOZAMBIQUE IN 2018 (SOURCE: NTP REPORT 2018) __________________ 26 
6. 
INVESTIGATIONAL PRODUCT ______________________________________________________ 27 
6.1 
TRUENAT TB PLATFORM/TB ASSAYS DEFINITION ________________________________________ 27 
6.2 
TRUENAT SYSTEM _____________________________________________________________ 27 
6.3 
ACQUISITION ________________________________________________________________ 28 
6.4 
STORAGE ___________________________________________________________________ 28 
6.5 
TEST HANDLING AND PERFORMANCE ________________________________________________ 28 
6.6 
ACCOUNTABILITY ______________________________________________________________ 28 
6.7 
EXPORT AND IMPORT PERMITS ____________________________________________________ 28 
6.8 
QUALITY CONTROL CHECK FOR INCOMING SHIPMENTS _____________________________________ 28 
6.9 
LOCAL PROCUREMENT __________________________________________________________ 28 
7. 
RATIONALE FOR THE STUDY _______________________________________________________ 29 
8. 
STUDY OBJECTIVES ______________________________________________________________ 30 
8.1 
PRIMARY OBJECTIVE ____________________________________________________________ 30 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
8.2 
SECONDARY OBJECTIVES _________________________________________________________ 30 
8.3 
ADDITIONAL OBJECTIVES _________________________________________________________ 30 
9. 
STUDY DESIGN__________________________________________________________________ 31 
9.1 
SUMMARY __________________________________________________________________ 31 
9.2 
INTERVENTION _______________________________________________________________ 31 
9.3 
STANDARD OF CARE (CONTROL) ____________________________________________________ 31 
9.4 
SETUP PERIOD (SURVEY OF STUDY CENTRES) ___________________________________________ 31 
9.5 
ASSIGNMENT OF INTERVENTION ___________________________________________________ 31 
9.5.1 
ALLOCATION CONCEALMENT MECHANISM ___________________________________________ 31 
9.5.2 
CLINIC RANDOMIZATION AND SEQUENCE GENERATION __________________________________ 31 
9.5.3 
IMPLEMENTATION ___________________________________________________________ 32 
9.5.4 
BIAS REDUCING MEASURES _____________________________________________________ 32 
9.6 
STUDY ENDPOINTS _____________________________________________________________ 32 
9.6.1 
PRIMARY ENDPOINT __________________________________________________________ 32 
9.6.2 
SECONDARY ENDPOINT ________________________________________________________ 33 
9.6.3 
ADDITIONAL ENDPOINTS _______________________________________________________ 33 
9.7 
STUDY POPULATION AND ELIGIBILITY CRITERIA __________________________________________ 33 
9.7.1 
INCLUSION CRITERIA __________________________________________________________ 33 
9.7.2 
EXCLUSION CRITERIA _________________________________________________________ 34 
9.8 
SCHEDULE OF EVENTS ___________________________________________________________ 34 
9.9 
PARTICIPATING SITES ___________________________________________________________ 35 
9.10 
CLINICAL LABORATORIES _________________________________________________________ 36 
TANZANIA: __________________________________________________________________________ 36 
MOZAMBIQUE: _______________________________________________________________________ 36 
9.11 
DATA COLLECTION AND HANDLING __________________________________________________ 37 
10. 
STUDY ASSESSMENTS __________________________________________________________ 38 
10.1 
VISIT 1: ____________________________________________________________________ 38 
10.2 
VISIT 2 AND 3 ASSESSMENTS ______________________________________________________ 38 
11. 
PATIENT ENROLMENT __________________________________________________________ 39 
11.1 
RECRUITMENT PROCEDURES ______________________________________________________ 39 
11.2 
PATIENT INFORMED CONSENT _____________________________________________________ 39 
11.3 
INCENTIVES AND EXPENSES _______________________________________________________ 40 
11.4 
EXCLUSION OF PARTICULAR GROUPS _________________________________________________ 40 
11.5 
PARTICIPANT WITHDRAWAL ______________________________________________________ 40 
12. 
STUDY PROCEDURES ___________________________________________________________ 40 
12.1 
VISIT 1 BASELINE VISIT __________________________________________________________ 40 
12.2 
VISIT 2: DAY 7 _______________________________________________________________ 41 
12.3 
VISIT 3: DAY 60 ______________________________________________________________ 41 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
13. 
STATISTICAL CONSIDERATIONS __________________________________________________ 42 
13.1 
POPULATIONS TO BE ANALYZED ____________________________________________________ 42 
13.2 
DESIGN CONSIDERATIONS ________________________________________________________ 42 
13.3 
RANDOMIZATION _____________________________________________________________ 42 
13.4 
DESCRIPTIVE STATISTICS _________________________________________________________ 42 
13.5 
ANALYSIS OF ENDPOINTS ________________________________________________________ 42 
13.7 
INTERIM ANALYSIS _____________________________________________________________ 44 
13.8 
SAMPLE SIZE DETERMINATION _____________________________________________________ 44 
TABLE 2: SELECTED SCENARIOS. COLOURS VARY WITH CLUSTER SIZE AND PREVALENCE. RED: FINAL SCENARIO. ______ 45 
14. 
DATA MANAGEMENT __________________________________________________________ 46 
14.1 
DATA MANAGEMENT PLAN _______________________________________________________ 46 
14.2 
DATA COLLECTION _____________________________________________________________ 46 
14.3 
SOURCE DOCUMENTS ___________________________________________________________ 46 
14.4 
DATA ENTRY _________________________________________________________________ 46 
14.5 
DATA HANDLING AND RECORD KEEPING ______________________________________________ 47 
15. 
MONITORING AND QUALITY ASSURANCE __________________________________________ 48 
15.1 
STUDY MONITORING ___________________________________________________________ 48 
15.2 
INSPECTION OF RECORD _________________________________________________________ 48 
15.3 
RECORD RETENTION ____________________________________________________________ 48 
15.4 
CONFIDENTIALITY OF PERSONAL DATA _______________________________________________ 48 
16. 
USER PREFERENCES (QUALITATIVE SUB-STUDY ASSESSING USABILITY, FEASIBILITY, AND 
ACCEPTABILITY)_____________________________________________________________________ 50 
16.1 
OBJECTIVES__________________________________________________________________ 50 
16.2 
GENERAL DESIGN AND PARTICIPANTS ________________________________________________ 50 
16.3 
SAMPLE SIZE AND SAMPLING ______________________________________________________ 51 
16.4 
INCLUSION & EXCLUSION CRITERIA _________________________________________________ 51 
16.5 
TOPIC GUIDE, DATA MANAGEMENT (PROTECTION) AND ANALYSIS _____________________________ 52 
17. 
ETHICAL CONSIDERATIONS ______________________________________________________ 53 
17.1 RISKS AND BENEFITS ________________________________________________________________ 53 
17.2 SAFETY AND INCIDENT REPORTING ______________________________________________________ 53 
17.3 BASIC PRINCIPLES __________________________________________________________________ 53 
17.4 INVOLVEMENT OF ETHICS COMMITTEES AND REGULATORY AUTHORITIES ____________________________ 53 
17.5 PROTOCOL AMENDMENT POLICY _______________________________________________________ 53 
17.6 DISCONTINUATION CRITERIA __________________________________________________________ 54 
17.7 FALSIFICATION OF DATA _____________________________________________________________ 54 
18. 
ADMINISTRATIVE CONSIDERATIONS ______________________________________________ 55 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
18.1 FINANCING ______________________________________________________________________ 55 
18.2 STUDY REGISTRATION _______________________________________________________________ 55 
18.3 PATIENT INSURANCE AND COMPENSATION ________________________________________________ 55 
18.4 TRAINING FOR STAFF INVOLVED IN THE STUDY ______________________________________________ 55 
18.5 PUBLICATION POLICY _______________________________________________________________ 55 
19. 
REFERENCES _________________________________________________________________ 56 
 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
Sponsor 
Sponsor 
FIND, The Global Alliance for Diagnostics
Sponsor Responsible 
Person 
 
 
 
 
 
 
 
Clinical Project Manager 
 
Dr Morten Ruhwald, MD PhD 
FIND, The Global Alliance for DiagnosticsCampus 
Biotech 
9 Chemin des Mines 
1202 Geneva 
Phone: +41 (0) 22 710 05 91 
Mobile: + 41 (0) 79 911 65 35 
Email: morten.ruhwald@finddx.org 
 
Dr Vinzeigh Leukes, PhD 
FIND, The Global Alliance for DiagnosticsCampus 
Biotech 
9 Chemin des Mines 
1202 Geneva 
Mobile: + 27 84 199 113 
Email: vinzeigh.leukes@finddx.org 
 
Medical Expert 
Dr Katharina Kranzer, PhD 
Division of Infectious Diseases and Tropical Medicine 
Medical Center of the University of Munich (LMU) 
D-80802 München, Leopoldstrasse 5 
Phone: +49 89 44005 98 05 
Mobile: +49 16092984509 
Email: aida@lrz.uni-muenchen.de 
 
Study Statistician 
Dr Stefano Ongarello 
FIND, The Global Alliance for Diagnostics 
9 Chemin des Mines 1202 Geneva 
Phone: +41 22 710 0953 
Mobile: +41 79 618 6567 
Email: stefano.ongarello@finddx.org 
 
Clinical Data Manager 
Dr Friedrich Riess 
Division of Infectious Diseases and Tropical Medicine 
Medical Center of the University of Munich (LMU) 
D-80802 München, Leopoldstrasse 5 
Phone: +49-89-4400-598-29 
Email: Friedrich.Riess@lrz.uni-muenchen.de 
 
Clinical study partners
 
Site Principal Investigator 
(PI) 
 
Dr. Nyanda Elias Ntinginya, PhD 
National Institute for Medical Research (NIMR) – Mbeya Medical Research 
Centre (MMRC) 
P.O. Box 2410 
Mbeya – Tanzania 
Phone: +255 25 250 3364 
Mobile: +255766243836/ 
Email: nelias@nimr-mmrc.org 
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Page 8 of 57 
Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
Site Co-PI 
Dr. Issa Sabi 
National Institute for Medical Research (NIMR) – Mbeya Medical Research 
Centre (MMRC) 
P.O. Box 2410 
Mbeya – Tanzania 
Phone: +255 25 250 3364 
Email: isabi@nimr-mmrc.org 
 
Investigator 
Dr. Chacha Mangu 
National Institute for Medical Research (NIMR) – Mbeya Medical Research 
Centre (MMRC) 
P.O. Box 2410 
Mbeya – Tanzania 
Phone: +255 25 250 3364 
Email: cmangu@nimr-mmrc.org 
 
Site Clinical Research 
Coordinator 
Dr. Elimina Siyame 
National Institute for Medical Research (NIMR) – Mbeya Medical Research 
Centre (MMRC) 
P.O. Box 2410 
Mbeya – Tanzania 
Phone: +255 25 250 3364 
Email: esiyame@nimr-mmrc.org 
 
Head of laboratory 
Mr. Bariki Mtafya 
National Institute for Medical Research (NIMR) – Mbeya Medical Research 
Centre (MMRC) 
P.O. Box 2410 
Mbeya – Tanzania 
Phone: +255 25 250 3364 
Email: bmtafya@nimr-mmrc.org 
 
Site Principal Investigator 
(PI) 
Dr. Celso Khosa, PhD 
Vila de Marracuene, Estrada Nacional, N ͦ1 
Parcela N 3943, Maputo Mozambique 
Phone: +258 2143814/427131 
Fax +258 21426547 
E-mail: Khosacelso@gmail.com 
 
Site Co-Principal 
Investigator (CO-PI) 
Dr. Sofia Viegas, PhD 
Vila de Marracuene, Estrada Nacional, N ͦ1 
Parcela N 3943, Maputo Mozambique 
Phone: +258 2143814/427131 
Fax +258 21426547 
E-mail: viegas_sofia@hotmail.com 
 
Site Principal Investigator 
(PI) 
Dr. Dinis Nguenha 
Centro de Investigação em Saúde de Manhiça (CISM) 
CP 1929 Maputo - Moçambique 
Phone: +258 21 810002 
Fax: +258 21 810181 
Email: dinis.nguenha@manhica.net 
 
Site Co-Principal 
Investigator (CO-PI) 
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- CONFIDENTIAL - 
Page 9 of 57 
Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
Dr. Alberto Garcia-
Basteiro, PhD 
C
e
n
Centro de Investigação em Saúde de Manhiça (CISM) 
CP 1929 Maputo - Moçambique 
Phone: +258 21 810002 
Fax: +258 21 810181 
Email: alberto.garcia-basteiro@manhica.net 
 
Site Research Coordinator 
Mr. Délio Elísio 
Centro de Investigação em Saúde de Manhiça (CISM) 
CP 1929 Maputo - Moçambique 
Phone: +258 21 810002 
Fax: +258 21 810181 
Email: delio.elisio@manhica.net 
 
Site Principal Investigator 
(PI) 
 
 
 
Dr. Jerry Hella 
Ifakara Health Institute 
Dar es Salaam Office 
Plot 463, Kiko Ave, Mikocheni 
P.O. Box 78 373 Dar es Salaam 
Phone: +255713787754 
Email: jhella@ihi.or.tz
Site clinical research 
coordinator 
 
 
 
 
Collaborator 
 
Mohamed Sasamalo 
Bagamoyo District Hospital 
P.O BOX 74 
Bagamoyo 
Phone: +255657609765 
Email: msasamalo@ihi.or.tz 
 
Dr. Claudia Denkinger 
Maria del Mar Castro MD 
Saima Bashir, PhD 
University Hospital Heidelberg 
Division of Tropical Medicine 
Im Neuenheimer Feld 324 
69120 Heidelberg, Germany 
Email : claudia.denkinger@uni-heidelberg.de, mcastronoriega@gmail.com, 
saima.arif@uni-heidelberg.de
 
 
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Page 10 of 57 
Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
Signature page (sponsor) 
 
Protocol Title: 
Molbio TruenatTM 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  
Trial Number: 
TB041 -3/1 
 
 
 
Herewith we approve the protocol for the TB-CAPT CORE Truenat trial version 4.0, dated 18th 
January 2023, and confirm that it contains all information necessary to conduct the study 
according to the ethical principles laid down in the Declaration of Helsinki, Good Clinical 
Practice and all applicable local regulations. 
 
 
 
 
 
 
Sponsor Responsible Person 
Dr. Morten Ruhwald  
FIND, The Global Alliance 
for Diagnostics
Date 
 
CLINICAL TRIAL COORDINATOR 
 
 
 
 
 
Medical Expert 
Date 
Dr. Katharina Kranzer 
 
 
OTHER CLINICAL TRIAL PARTNERS 
 
 
if applicable: Study Statistician 
Date 
Dr. Stefano Ongarello 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
optional: Clinical Trial Manager 
Date 
                 Dr. Vinzeigh Leukes 
 
 
 
 
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 
   
 
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

- CONFIDENTIAL - 
Page 11 of 57 
Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
Statement of Principal Investigator 
 
Protocol Title: 
Molbio TruenatTM 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 
Trial Number: 
TB041 -3/1 
 
In signing this page, I, the undersigned, agree to conduct the trial according to the protocol and ICH-GCP 
E6 (R2) guidelines and in compliance with applicable regulations. 
 
I will ensure that the requirements relating to obtaining Institutional Review Board (IRB)/ Independent 
Ethics Committee (IEC) review and approval are met. I will promptly report to the IRB/IEC any and all 
changes in the research activities covered by this protocol. 
 
I have sufficient time to properly conduct and complete the trial within the agreed trial period and I have 
adequate resources (staff and facilities) for the foreseen duration of the trial.   
 
I am responsible for supervising any individual or party to whom I delegate trial related duties and 
functions conducted at the trial site. Further, I will ensure this individual or party is qualified to perform 
those trial-related duties and functions. 
 
I certify that key individuals involved with the conduct of this trial, including myself, have completed GCP 
training and, if applicable, Human Subjects Protection Training. 
 
I understand that all information obtained during the conduct of the trial with regard to the subjects’ state 
of health will be regarded as confidential. No participant’s names or personal identifying information may 
be disclosed.  All participant data will be anonymized and identified by assigned numbers on all Case Report 
Forms, laboratory samples and other trial related information (such as essential documents) forwarded to 
FIND. Monitoring and auditing by FIND, and inspection by the appropriate regulatory authority(ies), will 
be permitted. 
 
I will maintain confidentiality of this protocol and all other related investigational materials. Information 
taken from the trial protocol may not be disseminated or discussed with a third party without the express 
consent of FIND. 
 
 
Clinical Trial Site:  
 
 
 
 
 
 
 
 
 
(Print) 
 
Name of Principal Investigator:  
 
 
(Print) 
Signature:  
 
Date:   
 
 
 
       DD/MMM/YYYY 
 
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Centro de Investigação em Saúde de Manhiça (CISM)
Dinis Bento Nguenha
05/May/2023

- CONFIDENTIAL - 
Page 12 of 57 
Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
Protocol History/Amendment Summary* 
 
Version number 
Release date 
Comments 
1.0 
26.06.2020 
Initial version 
2.0 
30.11.2020 
 
Formatting updates 
 
Change in Ifakara PI to replace Frederick 
Haraka with Jerry Hella 
 
Change in NIRM clinical site coordinator from 
Elizabeth Ntapara to Elimina Siyame 
 
Rephrase objectives for clarity 
 
Updated timelines 
 
Added secondary objective endpoint 
 
Clarify inclusion/exclusion criteria 
 
Removed reference to Xpert MTB/XDR 
 
Added detail on OpenClinica database system 
 
Updated risk/benefit section 
2.1 
4.02.2021 
 
Updated version and dates  
 
Added detail to inclusion criteria 
 
Added detail to patient enrollment  
 
Clarification in patient withdrawal  
 
Added detailed to sampling for socio-economic 
and cost data 
 
Update schedule of events 
2.2 
27.03.2021 
 
Removed “user appraisal” objectives 
 
Changes secondary objective related to costs 
and productivity (as it will only be measured at 
180 days) 
 
Added details on cost and productivity 
 
Rename “Study register” Study TB outcome 
worksheet as per the new name of the CRF 
where indicated 
 
Updated schedule of events 
3.0 -MZ 
16.11.2021 
 
Administrative clarifications in text 
 
Replaced the investigational device and assay 
(GeneXpert Omni and Xpert MTB/Rif Ultra) 
with the Molbio Truenat platform combined 
with TruenatTM MTB Plus and MTB-RIF Dx 
assays 
 
Changed follow-up time to 2 months and 
removed the face-to-face follow-up visit at 6 
months 
 
Added objectives of the qualitative sub-study 
and Ease of Use assessment 
 
Added Mozambique to Section 16: Description 
of the procedures, inclusion/exclusion criteria, 
data management and analysis for the 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
qualitative sub-study 
 
Changed sponsor responsible person from 
Samuel Schumacher to Dr. Morten Ruhwald 
 
Change in CISM Site Research Coordinator 
from Joaquim Cossa to Delio Elisio. 
4.0 
18.01.2023 
 
Added primary endpoint: in additional to the 
proportion, the count was added 
 
Cost and productivity endpoints were changed 
to include patient and health system costs 
 
The definition of successful treatment 
outcomes has been changed to ongoing 
treatment in view of the reduced follow-up 
time (60 days) 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
1. Abbreviations / Glossary of Terms 
ART 
 
 
Antiretroviral therapy 
AE 
 
 
Adverse events 
CFU 
 
 
Colony Forming Unit 
CISM 
 
 
Centro de Investigação em Saúde de Manhiça  
CRF 
 
 
Case Report Form 
DNA 
 
 
Deoxyribonucleic acid 
DST 
 
 
Drug Susceptibility Testing 
FIND 
 
 
Foundation for Innovative New Diagnostics 
HIV 
 
 
Human Immunodeficiency Virus 
IEC 
 
 
Independent Ethics Committee 
ICH-GCP 
 
 
International Council for Harmonisation – Good Clinical Practice  
IHI 
 
 
Ifakara Health Institute 
INS 
 
 
Instituto Nacional de Saúde 
LMU 
 
 
Ludwig-Maximilians-Universität 
LTFU 
 
 
Loss to Follow Up 
MDR-TB 
 
 
Multi-drug resistant tuberculosis  
MMRC 
 
 
Mbeya Medical Research Centre 
MOP 
 
 
Manual of Procedures 
MOH 
 
 
Ministry of health 
MTB 
 
 
Mycobacterium tuberculosis  
NIMR 
 
 
National Institute for Medical Research 
NTLP 
 
 
National Tuberculosis and Leprosy Control Programme  
Omni 
 
 
GeneXpert® Omni 
POC 
 
 
Point-of-Care 
RIF 
 
 
Rifampicin 
SAE 
 
 
Severe Adverse Events 
SOP 
 
 
Standard Operating Procedure 
SOC 
 
 
Standard of Care 
SSA 
 
 
Sub-Saharan Africa 
TB 
 
 
Tuberculosis 
TPP 
 
 
Target Product Profiles 
Xpert 
 
 
Xpert® MTB/RIF or Xpert® MTB/RIF Ultra 
WHO 
 
 
World Health Organization
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
2. Protocol synopsis 
 
Protocol Title 
TruenatTM platform combined with the Truenat TB assays for 
detection of tuberculosis (TB) and rifampicin resistance in adults 
with presumptive pulmonary tuberculosis at primary-level 
diagnostic centres in Tanzania and Mozambique: a cluster-
randomized controlled trial 
Protocol Code 
Project number TB041 -3/1 
Short Title 
TB-CAPT CORE Truenat trial 
Sponsor 
FIND, The Global Alliance for Diagnostics 
Study Centres 
Multicentre study in 4 sites in 2 countries (Mozambique and 
Tanzania) 
Name of investigational 
device 
- 
Primary study: 
- 
Referred to collectively in this protocol as: the Truenat 
platform and Truenat TB assays: 
- 
Devices: 
- 
Trueprep® AUTO v2 Universal Cartridge Based Sample Prep 
Device 
- 
Truelab® Duo Real Time Quantitative micro PCR Analyzer 
- 
TB Assay components:  
- 
Truelab® micro–PCR Printer (connected by Bluetooth) 
- 
Trueprep® AUTO MTB Sample Pretreatment Pack 
- 
Trueprep® AUTO v2 Universal Cartridge Based Sample Prep 
Kit 
- 
TruenatTM MTB Plus kits, consisting of Truenat chips, a 
Truepet® 6μl Precision Micropipette 
- 
TruenatTM MTB-RIF Dx kits, consisting of Truenat chips, a 
Truepet® 6μl Precision Micropipette 
 
Indication 
Investigation of outpatients presenting with symptoms suggestive 
of pulmonary tuberculosis (TB) 
Intervention and Control 
Groups 
Investigational group: 
 
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 
Control group (standard of care): 
Standard of care for TB testing using a combination of smear 
microscopy and laboratory (off-site) Xpert testing and may vary by 
clinic depending on availability of transport and stock of Xpert® 
MTB/RIF or Xpert® MTB/RIF Ultra cartridges (Xpert). 
Objectives 
Primary Objective: 
 
Evaluate the effect of testing for TB using the Truenat 
platform/TB assays combined with rapid communication 
(intervention arm), compared to standard of care (control 
arm) in primary health care clinics (“clinics” in the further 
documents) on TB diagnosis and treatment initiation for 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
microbiologically confirmed TB at 7 days from enrolment 
Secondary Objectives: 
 
Evaluate the effect of the Truenat platform/TB assays on 
time to TB treatment initiation at 60 days from enrolment: 
- for microbiologically confirmed TB cases 
- for clinically diagnosed TB cases 
- all TB cases (clinically diagnosed and 
microbiologically confirmed) 
 
Estimate the effect of the Truenat platform/TB assays on 
morbidity, mortality, on treatment loss to follow-up at 7 
and 60 days from enrolment 
 
Estimate the effect of Truenat platform/TB assays on total 
costs (patient costs and health system costs) and 
productivity 
Additional Objectives 
 
Evaluate the reliability of Truenat platform/TB assays as 
measured by rate of non-determined test results and 
platform failure 
User preferences  
 
To investigate user perspectives on the Truenat platform/TB 
assays (including perspectives of end-users such as patients, 
but also of professional users such as laboratory technicians, 
clinicians, nurses, and decision-makers) for use as a 
diagnostic test for outpatients presenting with symptoms 
suggestive of pulmonary TB tuberculosis (TB) 
 
To investigate and compare experiences and challenges with 
diagnostic testing for TB in patients using the different 
diagnostic approaches (Xpert® MTB/RIF, Xpert® MTB/RIF 
Ultra, microscopy, culture) 
 
To understand feasibility and preferences with regard to 
diagnosing TB and how Truenat platform/TB assays changes 
these 
 
To assess the usability and acceptability of Truenat 
platform/TB assays in the intended users 
Study Design 
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. A cluster refers to a 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
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. 
Population 
A total of 29 clinics will be randomized at the four participating sites 
aiming to enrol up to 150 adults (≥ 18 years of age) each (total 
approximately 4200) with signs and symptoms suggestive of TB. The 
number of clinics might be extended up to 37 due to the 
information gained in the setup period. 
Dependent on the loss to follow-up at 7 days, recruitment may 
need to be extended. 
Inclusion/Exclusion Criteria 
(Site) 
Based on information gained in the setup period sites will be 
included in the randomization process using the following criteria: 
Inclusion Criteria: 
Provision of TB treatment at the clinic 
Availability of electricity 
Willingness to participate 
 
Exclusion criteria: 
Patients with TB referred for treatment to other sites 
Sites with less than 10 patients registered for TB treatment per 
quarter 
Inclusion/Exclusion Criteria 
(Patients) 
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 who are 
able to produce a sputum sample 
 
Adults 18 years old and above (including pregnant women) 
who are able and willing to consent 
Exclusion criteria: 
 
Children and adolescents <18 years of age 
 
Circumstances that raise doubt on free, informed consent 
(e.g., in a mentally impaired person or a prisoner) 
 
Already diagnosed with TB 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
 
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 
Inclusion/Exclusion Criteria 
 
(User preferences)  
Adult aged ≥ 18 years old 
Either: (1) Routine healthcare worker participating in the CORE trial 
or (2) Patient tested or to be tested with the Truenat platform /TB 
assays as part of the study or (3) Decision maker involved with 
implementation of novel tests at the local, national and/or regional 
level. 
Evaluation Criteria 
(Endpoints) 
Primary endpoint: 
 
Absolute number and point estimate (with 95% CIs) of the 
proportion of enrolled participants who are diagnosed with 
microbiologically confirmed TB and are starting TB 
treatment within 7 days of enrolment 
Secondary endpoints: 
Diagnosis related endpoints: 
 
Estimate of the time to bacteriological confirmation of TB 
(up to 60 days) from enrolment 
 
Point estimate with 95% Cis of the proportion of patients 
treated for TB who are diagnosed up to 60 days from 
enrolment 
o microbiologically 
o clinically 
Treatment/outcome related endpoints: 
 
Point estimate with 95% Cis of the proportion of 
participants evaluated for pulmonary TB starting TB 
treatment with microbiological confirmation within 60 
days from enrolment 
 
Absolute number and point estimate (with 95% CIs) of 
the proportion of enrolled participants evaluated for 
pulmonary TB starting TB treatment regardless of 
microbiological confirmation within 7 and 60 days from 
enrolment 
 
Estimate of time to TB treatment initiation for those with 
microbiological confirmation and for all participants 
(censored at 60 days) from enrolment 
 
Point estimate of the proportion of patients with 
ongoing treatment (on treatment) among: 
o Participants diagnosed with TB either clinically or 
with microbiological confirmation 
o Participants clinically diagnosed with TB 
o Participants with microbiological confirmation of TB 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
Morbidity related endpoints: 
 
Prevalence of current cough, limited appetite, weakness at 
60 days from enrolment 
Cost and productivity related endpoints: 
 
Patients’ costs related to care  
Additional endpoints: 
Operational characteristics: 
 
Truenat platform / TB assay non-determined test results 
rates 
 
Rate of Truenat platform failure 
 
Statistical Considerations 
Randomization: 
Restricted randomization approach resulting in 6 to 8 strata applying 
factors site and size of the clusters (=clinics). The strata are 
constructed using variables site and size of the clinic, whereby 
appropriate coarsening of the size and balance criteria are applied. 
The number of strata may be increased in case of heterogeneity of 
sizes of the clusters (as indicated by information gained in setup 
period) 
Description: 
Baseline characteristics, such as demographic and analytical data 
will be summarized using descriptive statistical methods. 
Continuous data will be summarized using the mean, the median, 
standard deviation, the range (minimum and maximum value). 
Categorical values will be summarized using frequency counts and 
percentages. 
Analysis: 
Individual level analysis using generalized linear mixed model 
(GLMM) with logit link function, intervention (y/n) and stratum as 
fixed effects and cluster as a random effect. 
Sensitivity analyses based on cluster-level summaries will be 
applied. Adjustment for other variables (such as HIV status) may be 
considered in sensitivity analyses and will be described in detail in 
the statistical analysis plan (SAP). 
Sample size: 
For the purpose of sample size estimation, a matched design is 
regarded which is known to have a similar power in the range of 
number of clusters per treatment arm similar to this study (~15) 
since in that range the effects of gain of precision on one hand and 
the loss in degrees of freedom on the other hand are similar. 
Applying an alpha-level of 0.05, a power of 80%, 12% prevalence, 
LTFU-rates of 10% (diagn., control), 10% (pretreatment intervention), 
20% (pretreatment control), a cluster size of 150 and a within-pair 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
coefficient of variation (default value 0.25 acc. Hayes & Bennett 
1999), 13 clusters per study arm result (3900 patients). In order to 
address uncertainty, 1 additional cluster per treatment arm will be 
introduced, thus 14 cluster-pairs (28 clinics, 4200 patients) result. If 
the information collected in the setup phase indicates that some 
clusters will be unable to enroll 150 patients during the study period 
the number of cluster may be increased up to 36 
Study Timeline 
Period for ethics clearance 
Q4 2021- Q2 2022 
Setup period 
Q4 2021 - Q2 2022 
Import permits and importation 
Q1 2021 -Q3 2022 
Kick off / training meeting 
Q3 2022 
Training of sites on study procedures 
Q2 2022 
Training of staff on Truenat procedures 
Q2 2022 
First participant enrolled 
Q3 2022 
Last participant enrolled 
Q3 2023 
Complete follow-up 
Q4 2023 
Data cleaning: 
Q4 2023 
Data analysis: 
Q1 2024 
Final report:                                                               Q1 2024 
Total duration of study: 
                             31 months 
 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
3. Study schedule of events 
 
 
Visit 
Visit 1 
(V1-D1) 
Visit 2 
(V2-D7) 
Visit 3 
(V3-D60) 
Timeframe 
Day 1 
Day 7 
(Week 1) 
Day 60 
(Month 2) 
Procedure 
<48h 
Day 8 up to 
day 21 
Day 61 up to day 
90 
Informed consent 
x 
Eligibility assessment 
x 
Enrolment (study register) 
x 
Contact information (locator form) 
x 
(update) 
 
 Baseline questionnaire (CRF-V1-D1) 
x 
 Baseline questionnaire with detailed socioeconomic questions 
(CRF-V1-D1-SE) 
(x) 
 
 
 Investigational product testing 
(x) 
 
 
Follow-up questionnaire day 7 (CRF-V2-D7) – administered by 
telephone (3 attempts) if unsuccessful conduct home visit or 
call patient-nominated contact person 
 
x 
 
 Follow-up questionnaire day 60 (CRF-V3-D60) - administered 
by telephone (3 attempts) if unsuccessful conduct home visit or 
call patient-nominated contact person 
 
 
x 
 
Throughout follow-up data from the TB register and health facilities will be collected (study TB outcome worksheet) 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
 
4. Summary of the proposed research in lay terms 
Tuberculosis (TB) is the infectious disease that causes the highest number of deaths worldwide. In 
2017, about 1,6 million persons died of TB globally. 
While TB that is sensitive to commonly used medications rifampicin and isoniazid can be treated within 
6 months and mostly cured, TB with resistance to these medications requires a different, longer 
treatment. Besides the success in treating drug sensitive TB, it is believed that 4.3 million persons living 
with TB are missed every year. The reasons for this are that they cannot access quality diagnostic 
testing that would detect their disease at a healthcare facility close enough to their home. These are 
the so-called “missing millions” which may die due to undiagnosed TB or are diagnosed very late 
resulting in severe and irreversible lung damage. Also individuals with undiagnosed TB may spread the 
disease in their families and communities. 
Xpert MTB/RIF, a molecular diagnostic test developed by Cepheid, detects TB more accurately than 
microscopy and provides a result within 90 min. The diagnostic test is run on the GeneXpert platform. 
Smaller analysers are able to run 2-4 test concurrently while the infinity module can run up to 80 tests. 
Xpert MTB/RIF correctly diagnoses TB in 90% of individuals who have TB of the lung, this is in contrast 
to microscopy (still widely used) which only diagnoses about 50% of individuals with TB. Xpert MTB/RIF 
has the added advantage that it rapidly detects rifampicin (RIF) resistance. Patients diagnosed with 
rifampicin resistance can thus be referred to appropriate treatment. Xpert MTB/RIF was endorsed by 
WHO in 2011, and many countries are using the test (or planning to use it) as primary TB diagnostic 
replacing microscopy. A newer similar version of the test Xpert MTB/RIF Ultra is even more sensitive 
than the “conventional” Xpert MTB/RIF and detects TB in 95% of individuals who have the disease in 
their lungs. This Xpert MTB/RIF Ultra was endorsed by WHO in 2017. 
Another rapid molecular platform and assay the Molbio Truenat platform (consisting of the Trueprep 
DNA extraction device and the Truelab micro-PCR machine) and the Truenat MTB Plus assay for 
detection 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 (collectively referred to as the Truenat 
TB assays). The system is 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. Extracted DNA eluate from samples testing MTBC-positive can be 
used for RIF-resistance reflex testing. The limit of detection was determined to be 100 CFU/ml sputum 
sample which is similar to the widely used Xpert MTB/RIF.  Despite the successful roll-out of the Xpert 
MTB/RIF, which is more sensitive than microscopy, across Africa TB notifications have not increased 
and the impact on mortality remains uncertain. Most GeneXpert machines are placed in central or 
district laboratories requiring sample transport from primary health care clinics (where patients are 
usually seen) to the laboratory. Once the sample is tested, the results are sent back to the primary 
health care facility and the patient will have to be called back to start treatment. There are a number 
of bottlenecks across the diagnostic TB pathway, which results in substantial attrition during the 
diagnostic process. Essential steps include the individual accessing care, the health care worker 
referring the individual for TB investigations, the specimen being sent for TB diagnostics and the results 
being returned. Initiation of appropriate treatment relies on timely receipt of laboratory results and 
the patient returning to clinic. The proposed study aims to address some of the bottlenecks by bringing 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
the diagnostic device closer to the patients in the primary health clinic. 
The Truenat MTB Plus assay runs on the Trueprep/Truelab platform and has similar performance 
characteristics as the Xpert MTB/RIF run on the GeneXpert platform. The Truenat platforms/TB assays 
have several advantages over the GeneXpert platform making them more suitable for placement at 
primary health care facilities. The standalone platforms are 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. 
 
For this study we will randomize 29-37 primary health care facilities to diagnosing persons with signs 
and symptoms suggestive of TB of the lung using the existing diagnostic algorithm (mostly microscopy 
or off-site Xpert testing) or to placing Truenat platform at the facility to enable Truenat MTB Plus and 
Truenat MTB-RIF Dx testing on site.  
Whether or not the Truenat platform/TB assays will improve the TB diagnostic pathway will be 
measured across a number of indicators: time to TB treatment, proportion of patients with laboratory 
confirmed TB and number of deaths. We will also ask the staff at the health care facilities operating 
the machine about their experience (ease of use, test failure rate and other problems encountered 
when operating the machine). 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
 
5. BACKGROUND INFORMATION 
 
5.1 
Tuberculosis epidemiology 
Tuberculosis (TB) remains the leading infectious killer globally with 1.6 million deaths each year of 
which 300,000 were associated with HIV in 20171; 10 million new cases occur annually 
disproportionately affecting disadvantaged populations. TB is recognised to be both preventable and 
curable, yet 40% of people newly affected remain undiagnosed1, and millions do not receive quality 
care each year.2,3 
Relative to the population, the number of incident TB cases (per 100 000 population per year) has been 
falling slowly, as has the number of deaths. Worldwide, TB incidence decreased at about 2% per year.1 
The fastest regional declines from 2013 to 2017 were in the world health organization (WHO) European 
(5% per year) and African Region (4% per year). In the same 5 years, particularly impressive reductions 
(4–8% per year) occurred in southern Africa following a peak in the HIV epidemic, and the expansion 
of TB and HIV prevention and care. However, to achieve the sustainable development goals and End 
TB Strategy targets set for 2030 the annual decline in the global TB incidence rate would need to be 
accelerated to an average of 17% per year. 
While progress has undoubtedly been made, the disease burden in Sub-Saharan Africa (SSA), and 
particularly southern Africa, remains incredibly high. This is due to the HIV-driven TB epidemic, which 
resulted in a 500% rise in TB case notifications between 1985 and well into the late 1990s in some SSA 
countries including Mozambique and Tanzania.4,5 TB case notifications in these countries still remain 
increased compared to the pre-HIV era and over 50% of TB cases in SSA are co-infected with HIV. Of 
the 48 high TB, HIV-TB and MDR (multi-drug resistant)-TB (which is TB resistance to at least rifampicin 
and isoniazid) burden countries 21 are African. Furthermore 8 of 14 countries featuring on all three 
high burden lists are located in Africa. Mozambique is one of those countries facing a triple burden of 
TB, HIV-TB and MDR-TB in the context of a national adult HIV prevalence of 13.2%, while Tanzania is a 
high TB and HIV-TB burden countries. 
 
5.2 
Limited diagnostic capacity in sub-Saharan Africa 
Timely and appropriate diagnosis and treatment is the key to reduce TB mortality, morbidity and 
prevent transmission. However, almost half (4.3 million) of the 10 million TB cases and more than two- 
thirds (71%) of the MDR-TB cases remain undiagnosed.1 The main reasons are inaccessibility of 
diagnostics and attrition during the diagnostic process.6-10  
The Xpert MTB/RIF (Cepheid, Sunnyvale, CA) a rapid molecular test with 90% sensitivity and 98% 
specificity to diagnose TB and rifampicin resistance has revolutionised TB diagnostics.11-13 The test was 
endorsed by the WHO in 2011 and a newer and more sensitive version, the Xpert® MTB/RIF Ultra 
(Ultra) has been endorsed more recently.14,15 South Africa was the first country to rollout the Xpert 
MTB/RIF nationwide as replacement for smear microscopy. In comparison with South Africa, access to 
Xpert MTB/RIF testing is far more limited in other SSA countries, and smear microscopy (which has low 
sensitivity for TB and cannot determine drug susceptibility) remains the main tool for TB diagnosis.16-
18  However, even in SSA countries that have rolled out Xpert MTB/RIF testing remains a centralised 
service, and limited capacity and financial constraints mean that Xpert MTB/RIF is often restricted  to 
high risk groups.17-19 Furthermore while Xpert MTB/RIF has increased the proportion of 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
microbiologically confirmed TB and for the first time enables drug susceptibility testing (DST) for 
rifampicin (RIF), DST for other first and second line drugs such as isoniazid and moxifloxacin is only 
available at central level (mainly at the national reference laboratories). 
 
 
Figure 1: TB diagnostic pathway 
 
As shown in Figure 1, there are a number of bottlenecks across the diagnostic pathway for TB, which 
results in substantial attrition during the diagnostic process. Essential steps include the individual 
accessing care, the health care worker referring the individual for TB investigations, the specimen being 
sent for TB diagnostics and the results being returned. Initiation of appropriate treatment relies on 
timely receipt of laboratory results and the patient returning to clinic. Many SSA countries have 
reported significant attrition along the diagnostic pathway.20-24 
 
In 2014 the WHO convened a stakeholder meeting aimed at establishing high-priority target product 
profiles (TPPs) for new TB diagnostics.25 A point-of-care (POC) sputum-based test to replace smear 
microscopy for detecting pulmonary TB (the smear-replacement test) was identified as one of four 
high  priority TB diagnostics. The Xpert MTB/RIF using the GeneXpert platform falls short of this TPP on 
a number of WHO ASSURED criteria for evaluating POC devices for resource-limited environments. 
ASSURED stands for affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free and 
deliverable to end-users. The current GeneXpert platform and TB assays are sensitive, specific, user- 
friendly and relatively robust. However, Xpert MTB/RIF and Ultra take 90 and 70 minutes respectively. 
The platform needs continuous electricity supply (or a powerpack of considerable size), cannot be 
Clinic
Diagnos c Centre
Delay and loss of specimens:
Lack of specimen tracking
Infrequent transport
Impassable roads
Delay and loss of results:
No electronic repor ng
Infrequent transport
Impassable roads
Quality of care:
Staff shortage
Staff knowledge
Staff awareness
Diagnos c capacity:
Staff shortage
Machine throughput
Risk factors for TB
• TB contact
• Previous TB
• HIV, Diabetes
• Migrants
• Prisons
• Mines
Access to diagnosis
and treatment
Financial constraints
Distance
Migrants
Limited awareness
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
operated at high temperatures, is sensitive to dust and the software requires either a laptop or a 
desktop computer. This limits the use of the GeneXpert platform in primary health care clinics, where 
these conditions are often not met.  Some of these shortcomings are overcome by the new Truenat 
platform and TB assays. 
 
5.3 
GeneXpert implementation in Tanzania 
The majority of the more than 1000 TB diagnostic facilities in Tanzania still use smear microscopy as 
their primary diagnostic tool. Roll out of Xpert MTB/RIF started in 2011 with a total of 67 GeneXpert 
devices placed across the country by 2014.17 Operational challenges include logistics of sample 
transport, unreliable electric power supply, lack of maintenance of the GeneXpert devices, inadequate 
funds for consumables and servicing contracts and limited expertise regarding supply chain 
management and stocks. 
 
5.4 
GeneXpert implementation in Mozambique 
The Xpert MTB/RIF was adopted as the initial diagnostic tool in all presumptive TB cases in 2016. 
However, smear microscopy continues to be the main diagnostic and treatment monitoring tool for 
TB. The number of devices has been increasing with 32 in 2014, 85 in 2017 and 109 in 2019. The 
Ministry of Health (MoH) aims to have at least one device available in every district in the country, the 
facility with the device will act as the reference center for TB diagnosis in that district. 
 
 
 
Figure 2: GeneXpert coverage in Mozambique in 2018 (Source: NTP report 2018) 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
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6. INVESTIGATIONAL PRODUCT 
 
All products used for clinical decision-making, including the Truenat platform and the Truenat TB assays 
for detection of MTBC and RIF-resistance already have CE-IVD mark. The WHO has endorsed the 
Truenat platform and Truenat MTB Plus and Truenat MTB RIF-Dx assays for diagnosis of TB and 
detection of RIF resistance in 2020.26,27  
 
6.1 
Truenat TB Platform/TB Assays definition 
 
The following Molbio Truenat equipment and materials used in this study are referred to collectively in 
this protocol as: the Truenat TB platform: 
- 
Equipment: 
- 
Trueprep® AUTO v2 Universal Cartridge Based Sample Prep Device 
- 
Truelab® Duo Real Time Quantitative micro PCR Analyzer 
- 
Truelab® micro–PCR Printer 
- 
TB Assay components: 
- 
Trueprep® AUTO MTB Sample Pretreatment Pack 
- 
Trueprep® AUTO v2 Universal Cartridge Based Sample Prep Kit 
- 
TruenatTM MTB Plus kits, containing Truenat chips, a Truepet® 6μl Precision Micropipette 
- 
TruenatTM MTB-RIF Dx kits, containing Truenat chips, a Truepet® 6μl Precision Micropipette 
 
No other Molbio products are to be used in the intervention arm of this protocol. 
 
6.2 
Truenat system 
The Truenat (Molbio Diagnostics, Goa, India) testing system (Trueprep DNA extraction device and the 
Truenat micro-PCR machine) uses portable, battery operated devices to rapidly detect MTBC and RIF- 
resistance. The assay for detecting MTBC DNA is Truenat MTB Plus, while the assay to detect RIF 
resistance is the Truenat MTB-RIF Dx. The system involves two main devices: the Trueprep AUTO v2 
Universal Cartridge based Sample Prep Device for the automated extraction and purification of DNA, 
and the Truelab Real Time micro PCR Analyzer for performing real-time polymerase chain reaction 
(PCR), resulting in the semi-quantitative detection of MTBC. The system uses room temperature stable 
reagents (Trueprep AUTO Sample Pre-treatment and Prep kits) and Truenat micro PCR chips. The 
system is designed to be operated in peripheral laboratories with minimal infrastructure. In 2020 WHO 
has reviewed performance characteristics of this molecular point-of-care test for TB and endorsed the 
test for TB diagnosis. It takes about 25 minutes to do the DNA extraction and another 35 minutes to 
diagnose TB. Extracted DNA eluate from samples testing MTBC-positive can be used for rifampicin 
resistance reflex testing. The limit of detection was determined to be 100 CFU/ml sputum sample 
which is similar to the widely used Xpert MTB/RIF.28  
In the control arm, standard of care will be conducted according to country specific protocols and 
guidelines. This will be a combination of smear microscopy at level 1 and/or Xpert MTB/RIF or Xpert 
MTB/RIF Ultra. 
The Truenat testing system has great potential to enable true POC testing for TB and could be placed 
at the lowest tier of the health care system (i.e. primary health care clinics) potentially reducing 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
attrition along the diagnostic pathway. This in turn may reduce diagnostic delays and loss to follow-up 
during the diagnostic process and before initiating treatment resulting in decreased morbidity, 
mortality and reduced costs for the patient and health care system 
 
6.3 
Acquisition 
Procurement of the investigational products will be done through FIND, who will coordinate shipments 
from the manufacturer. It is the responsibility of each trial site to maintain an updated inventory of the 
trial materials and to inform FIND immediately if additional materials are required. The investigator or 
designee must confirm appropriate temperature conditions have been maintained during transit for 
the investigational product received and any discrepancies are reported and resolved before its use. 
 
6.4 
Storage 
Procedures for product storage and disposal will be described in the Trial Manual. The 
investigational product must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labelled storage conditions with access limited 
to the investigator and authorized site staff. 
 
6.5 
Test handling and performance 
Testing using the investigational products will be performed according to the manufacturer’s 
instructions outlined within the Trial Manual. Only sputum samples from participants enrolled in 
the trial will be processed with the investigational product and only authorized site staff will be 
responsible for processing. 
 
6.6 
Accountability 
The investigator is responsible for trial intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). Investigational Product 
Accountability logs filled at each site will ensure the proper follow-up of the used, failed and 
remaining investigational products. Further guidance and information for the final disposition 
of unused investigational product are provided in the Trial Manual. 
 
6.7 
Export and import permits 
It is expected that most countries will require import permits for receiving the investigational 
materials. Local sites are responsible for making import permit applications in a timely 
manner. 
 
6.8 
Quality control check for incoming shipments 
Upon arrival of each new shipment of assays, the sites will conduct and document an 
incoming quality check following the Trial Manual. New lots may only be used after this quality 
check is successfully passed. 
 
6.9 
Local procurement 
Sites are responsible for assessing their needs and procuring any supplies, reagents and kits 
needed for the trial that are locally available in order to include these costs in the trial budget. 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
 
7. RATIONALE FOR THE STUDY 
 
The Truenat platform/TB assays could in principle enable more rapid treatment initiation and thus 
reduce pre-treatment loss to follow up. However, it is uncertain whether this potential for 
improvement can and will be realised when implemented as part of routine practice. 
This cluster randomized trial aims to assess whether improvements in patient outcomes are truly 
achieved using a new diagnostic strategy involving the Truenat platform and the Truenat MTB Plus and 
the Truenat MTB-RIF DX assays implemented in primary health care in Tanzania and Mozambique. In 
addition, data on operational characteristics of the Truenat platform/TB assays will be determined. 
The findings of this trial will inform policy for decisions on use and scale up of the Truenat platform/TB 
assays for TB diagnosis in resource- limited settings. 
 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
8. STUDY OBJECTIVES 
 
8.1 
Primary objective 
The primary objective is to evaluate the effect of Truenat platform/TB assays (intervention arm) 
combined with rapid communication of results compared to SOC on TB diagnosis and treatment 
initiation for microbiologically confirmed TB at 7 days from enrolment. 
 
8.2 
Secondary objectives 
The secondary objectives are: 
 To evaluate the effect of the Truenat platform/TB assay on time to TB treatment initiation at 60 
days from enrolment: 
 
for microbiologically confirmed TB cases 
 
for clinically diagnosed TB cases 
 
all TB cases (clinically diagnosed and microbiologically confirmed) 
 Estimate the effect of the Truenat platform/TB assays on morbidity, mortality and on treatment 
loss to follow-up at 7 and 60 days from enrolment 
 Estimate the effect of Truenat platform/TB assays on total costs (patient costs and health system 
costs)  and productivity  
 
8.3 
Additional objectives 
The additional objectives are: 
 To evaluate the reliability of Truenat platform/TB assays as measured by rate of non-determined 
test results and platform failure 
 User preferences  
 
To investigate user perspectives on the Truenat platform/TB assays (including perspectives of 
end-users such as patients, but also of professional users such as laboratory technicians, 
clinicians, nurses, and decision-makers) for use as a diagnostic test for outpatients presenting 
with symptoms suggestive of pulmonary TB tuberculosis (TB) 
 
To investigate and compare experiences and challenges with diagnostic testing for TB in 
patients using the different diagnostic approaches (Xpert® MTB/RIF, Xpert® MTB/RIF Ultra, 
microscopy, culture) 
 
To understand feasibility and preferences with regard to diagnosing TB and how Truenat 
platform/TB assays changes these 
 
To assess the usability and acceptability of Truenat platform/TB assays  in the intended users 
 
 
 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
9. STUDY DESIGN 
 
9.1 
Summary 
This is a cluster randomized controlled trial to evaluate the effect of placing Truenat platforms /TB 
assays at clinics in Mozambique and Tanzania. 
In a setup period (survey of study centers) before randomization, the 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 with rapid communication of 
results on time to treatment initiation of microbiologically confirmed TB. Facilities will be randomly 
allocated to the SOC (control), or Truenat platform/TB assays (intervention). A cluster refers to a clinic. 
The clinics will be randomly assigned to intervention or control arm following a restricted 
randomization strategy, whereby 6-8 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 during the setup period and 
may be increased, typically 1 or 2 strata per site will be established. 
Individual level analysis will be performed with strata and intervention as fixed effects and cluster as 
random effect. 
 
9.2 
Intervention 
The intervention is the placements of the Truenat platform/TB assays at primary health care clinics 
combined with rapid communication of results and same day TB treatment initiation. 
 
9.3 
Standard of care (control) 
All control clinics will have access to off-site Xpert testing. The degree to which patients and/or samples 
are referred for Xpert testing will vary across clinics and potentially across time dependent on 
availability of transport. 
 
9.4 
Setup period (survey of study centres) 
During the setup period, the sites will be asked to collect TB notification numbers per quarter for each 
of the clinics for the period 1/2018-6/2020. 
From this information, the number of adults (“size of a clinic”) predicted to be investigated for TB at 
each of the clinics will be estimated. 
 
9.5 
Assignment of intervention 
 
9.5.1 
Allocation concealment mechanism 
The intervention will be allocated to clinics (i.e., clusters) rather than to individuals. Clinics will be 
identified and recruited before randomization, i.e. the allocation sequence will be concealed until 
participating clinics have agreed to participation. 
 
9.5.2 
Clinic randomization and sequence generation 
Taking into account the strata, a restricted randomisation approach will be applied to achieve balance 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
between the treatment arms.29 Among all possible distributions of clusters within strata those which 
are balanced due to specific stratification variables will be used. This stratification will be by site and 
size of clinic. In addition, the same or similar number of clusters (max. difference=1) should be 
allocated to each treatment arm within each stratum. The number of strata per site will depend on 
heterogeneity of the sizes of the clinics as established during setup period. Typically, 1 or 2 strata per 
site will be established. A total of 6-8 strata are expected but might be increased dependent on the 
results of the setup period. All possible allocations will be established, whereby balance criteria 
covering a prespecified variability of the stratification variables within a stratum will be applied. The 
size of the clinic (number of TB patients within a 2-month period) should not differ more than 20%. 
The allocations will be checked for validity, especially whether the clusters are spread independently 
among the allocations. If this is not the case, the balance criteria will be chosen less restrictive. If the 
number of allocations excess 10,000, a subsample is drawn. Finally, one of the allocations will be chosen 
randomly. 
 
9.5.3 
Implementation 
Clusters will be identified and asked to be part of the study by staff of participating sites. The allocation 
sequence will be generated by the trial statistician. The allocation to be applied is chosen randomly. All 
eligible individuals within each cluster will be enumerated and those willing to participate included in 
the study. 
 
9.5.4 
Bias reducing measures 
The objective of the trial is to assess the Truenat platform/TB assays in clinical care. The use of Truenat 
platform/TB assays does not allow blinding of clinicians and participants in this trial. The trial-related 
procedures will be embedded into the routine practice at the primary-level facility. Data analysts will be 
blinded to intervention allocation. 
Randomisation takes place on a cluster level rather than for the individual patients to avoid 
contamination between the arms within a health facility. Since clinics will be relatively far apart, 
contamination is unlikely. 
We will contact participants for the 7- and 60-day outcomes by telephone to investigate whether more 
diagnostics available at the level of the primary health care facility (without the need to refer samples) 
result in more microbiologically confirmed cases and more rapid treatment initiation. Losses to follow- 
up pre-diagnosis and during treatment are among the endpoints of the trial. There is a chance that 
contacting the participants after 7 days may influence their treatment seeking behaviour even in the 
control arm and reduce loss to follow-up. By keeping contact with trial participants to a minimum (i.e., 
two time points) we hope to limit the impact on treatment seeking behaviour. 
 
9.6 
Study endpoints 
Primary and secondary endpoints are summarised in Table 1. 
 
9.6.1 
Primary endpoint 
The primary endpoint is the estimate of the number and proportion of participants with microbiological 
confirmation starting TB treatment within 7 days of their first visit among enrolled participants. 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
9.6.2 
Secondary endpoint 
Secondary endpoints include diagnosis and treatment related endpoints. 
Diagnosis related endpoints: 
 Time to bacteriological confirmation of TB (up to 60 days) from enrolment 
 Number and proportion of patients treated for TB who are diagnosed within 60 days of enrolment 
 
microbiologically 
 
clinically 
Treatment/outcome related endpoints: 
 Number and proportion of participants with signs and symptoms suggestive of pulmonary TB 
starting TB treatment with microbiological confirmation within 60 days from enrolment 
 Number and proportion of participants with signs and symptoms suggestive of pulmonary TB 
starting TB treatment without microbiological confirmation within 7 and 60 days from enrolment 
 Number and proportion of participants with signs and symptoms suggestive of pulmonary TB 
starting TB treatment regardless of microbiological confirmation within 7 and 60 days from 
enrolment 
 Time to TB treatment initiation for those with microbiological confirmation and for all participants 
(censored at 60 days) from enrolment 
 Number and proportion of patients with ongoing treatment(on treatment) among: 
 
Participants diagnosed with TB either clinically or with microbiological confirmation 
 
Participants clinically diagnosed with TB 
 
Participants with microbiological confirmation of TB 
Morbidity related endpoints: 
 
Prevalence of current cough, limited appetite, weakness at 60 days from enrolment  
Cost and productivity related endpoints 
 
Patient costs related to diagnosis and treatment  
 
9.6.3 
Additional endpoints 
Operational characteristics 
 Truenat TB assays rate of non-determined test results 
 Rate of Truenat platform device failure 
 
9.7 
Study population and eligibility criteria 
The trial population will comprise consecutively recruited adults presenting with symptoms suggestive 
of pulmonary TB at primary-level facilities (clinics). Presumptive pulmonary TB patients will receive 
diagnostic procedures according to the random allocation assigned to the clinic. Clinics randomized to 
the intervention will have Truenat platforms placed in the facility and sputum samples will be 
investigated with the Truenat MTB Plus and the Truenat MTB-RIF DX assays. In addition, procedures 
will be put in place to ensure rapid communication of results and same day TB treatment initiation. 
These procedures will be site specific and informed by the local context. Participants accessing clinics 
randomized to SOC will be investigated according to the national standard, which in most cases will be 
smear microscopy and/or Xpert testing.  
 
9.7.1 
Inclusion criteria 
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Protocol short title: TB-CAPT CORE Truenat trial 
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Protocol Version: 4.0 
 
 
 
 
 
Presumptive pulmonary TB patients, 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 and who are 
able to provide a sputum sample 
 
Adults 18 years old and above (including pregnant women) who are able and willing to consent. 
 
9.7.2 
Exclusion criteria 
 
Children and adolescents <18 years of age 
 
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 
 
Enrolment into the trial at a previous visit 
 
9.8 
Schedule of events 
Consent, recruitment, and baseline questionnaire will be done by the primary health care nurses in 
each of the clinics. Microscopists in the intervention clinics will be trained in using the Truenat platform 
and will be performing the Truenat MTB Plus and the Truenat MTB-RIF DX assays. Care providers at 
the intervention clinics will be trained in how to interpret Truenat TB assay results. Referral pathways 
for patients diagnosed with RIF resistant TB are already in place in both countries. These referral 
pathways will be re-iterated as part of the training. Each site will develop procedures to ensure rapid 
communication of Truenat platform/TB assays results to the clinician. Also measures will be taken to 
ensure same day TB treatment initiation.  
For all participants who do not own a phone at the time of enrolment, a close contact number will be 
registered, otherwise, a home visit will be conducted for the study follow-up visits.  
Staff in the control clinics will receive refresher training on the national guidelines on how to diagnose and 
treat TB. Referral pathways for drug resistant TB will be discussed in these trainings.  
Participants will be asked about their contact details (phone number, phone number of a trusted proxy 
and home address) to enable follow-up. Each participant will get a study-ID. 
Contact details will be recorded in a locator form. Study-ID, names, age, sex, and date of first 
presentation will be noted in a study register, which will remain in the clinic. The study registers will 
be checked against the TB register by the research team supervisor every week. If and when a patient 
has started TB treatment, the TB-register number and the date of TB treatment initiation will be 
documented in the study TB outcome worksheet. A paper-based clinical report form (CRF) will be used 
to document the baseline (day 1) questionnaire (V1-D1). No names, addresses or contact details will 
be entered on the CRFs. Participants will be identified by study-ID (see above). The only identifiable 
information recorded on CRFs will be age and sex. The V1-D1 will be retrieved from each clinic in 
regular intervals. The V1-D1 will be entered into an electronic database centrally in real time to enable 
timely follow-up by the research team by phone. The locator forms (including the phone numbers and 
addresses) will not be entered electronically but kept in locked cupboards. Timely data entry of V1-D1 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
will allow creating lists of study-IDs for locator forms to be retrieved and follow-up to be coordinated. 
A proportion of participants (5-10%) will be sampled, by selecting every tenth participant, across 
intervention and control clinics and across both countries to administered all of the questions of the 
baseline questionnaire plus some additional questions about costs of care-seeking. The data will be 
documented on the V1-D1-SE CRF. All clinics will be given a list of study-ID numbers identifying those 
participants who will be asked to answer the V1-D1-SE CRF before the start of enrolment. 
Sites, which have the capacity to perform real-time data entry into electronic tablets, will be able to 
do so (as an alternative to paper-based CRFs). 
Visit 2 (Day 7) and Visit 3 (Day 60) interviews will be conducted between days 8-21 and 61-90 post 
enrolment, respectively. Three attempts will be made to contact the participant. If the participant 
cannot be reached, the trusted proxy (documented on the locator form) will be contacted and asked 
about the participant’s whereabouts. The trusted proxy will be asked on how best to contact the 
participant (i.e., other phone number or home visit). A home visit will be conducted for participants 
that cannot be reached by phone. A maximum of three home visit attempts will be made. Visit 2 and 
Visit 3 interviews will be recorded on paper-based CRFs (V2-D7, V3-D60) and entered electronically. 
Face-to-face visits may be considered for the Visit 3 interviews if a participant was sampled for a more 
extended socio-economic questionnaire (see above and below).  
Only the study-ID and not the participant’s name will be entered on the Truenat platform when a 
sample is tested. Pseudonymised Truenat TB assays results will be automatically uploaded to a secure, 
encrypted server at FIND using a Global SIM card on each Truelab micro PCR device in the intervention clinic 
on a regular basis using a File Transfer Protocol (FTP) or a similar system. This data maintains 
participant’s confidentiality thereby ensuring subject’s anonymity. Laboratory results such as smear 
microscopy or off-site Xpert MTB/RIF results will be captured by the research team supervisor and 
recorded in the study TB outcome worksheet. 
Assay data (rates of non-determined results) and device data (instrument failures) will be securely 
uploaded to the FIND server and access by the trial data manager. Maintenance logs will be reviewed 
at the end of the study. 
All sputum samples of participating patients in the intervention clinics will undergo Truenat platform/TB 
assays testing. The study-ID will be used as an identifier.  
 
9.9 
Participating sites 
This study will be coordinated by two research institutions (sites) in each country and a total of 29 to 
37 primary health care clinics (clinics).  
Tanzania 
1. Ifakara Health Institute (IHI) 
2. National Institute for Medical Research (NIMR/MMRC) 
 
Mozambique 
1. Centro de investigação de Saúde de Manhiça 
2. Instituto Nacional de Saúde (INS) 
 
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Protocol Version: 4.0 
 
 
 
 
If a primary health care clinic has to stop recruitment during the study, another clinic may be selected 
to replace that clinic. An additional 8 clinics have been selected as backup clinics, 6 by NIMR-MMRC 
and 2 by INS. 
 
9.10 Clinical laboratories 
Health care providers may be asked to send a sputum sample for culture for patients with high suspicion 
of TB but negative molecular results according to national guidelines. These samples will be processed 
in the following laboratories: 
 
Tanzania: 
TB Laboratory 
NIMR Mbeya Medical Research Centre, 
Hospital Hill Rd, P.O.Box 2410, 
Tel: +255 25 250 3364, 
Mbeya, Tanzania 
 
TB Laboratory, 
Ifakara Health Institute, 
Bagamoyo Research and Training Centre, 
P. O. Box 74, 
Tel:  +255 23 244 0065 
Bagamoyo, 
Pwani, Tanzania 
 
Mozambique: 
Laboratório Nacional de Tuberculose 
Instituto Nacional de Saúde 
Av. Eduardo Mondlane, No 1653 
Maputo, Moçambique 
Tel/Fax: (+258) 21 311 038 
Carla Madeira BSc, MSc 
Email: carlamariamadeira@hotmail.com 
 
Biosafety Level 3 (BSL3) TB laboratory 
Centro de Investigação em Saúde de Manhiça 
CP 1929 Maputo – Moçambique 
Tel./Fax: (+258) 21 810002/ 21810181 
Belén Saavedra Cervera BSc, Clinical Microbiologist, MSc 
Email: belen.saavedra@manhica.net 
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9.11 Data collection and handling 
There will be a maximum of three questionnaires administered per participant: at Visit 1 (baseline; V1-
D1 or V1-D1-SE), Visit 2 (Day 7; V2-D7) and Visit 3 (Day 60; V3-D60 or V3-D60-SE). All interviews will be 
documented on paper CRFs entered electronically, either centrally at the four sites, or at the clinics, 
into the OpenClinica eCRF/data base located at the LMU. Direct electronic data entry will be supported 
if a research site has the capacity to do that. The paper CRFs (V1-D1) will be retrieved from clinics on a 
weekly basis and stored at the central site or entered at the clinic. Data entry of V1-D1 will need to be 
entered within 6 days of enrolment as it is particularly critical to support the conduct of the V2-D7 
phone calls. 
V2-D7 and V3-D60 questionnaires will be administered mainly by phone by the research team, entered 
into the database and filed and stored centrally at the sites. For a subset of participants (approximately 
50 per site) a more detailed socio-economic questionnaire (V1-D1-SE) will be conducted at baseline 
and at the last visit (V3-D60-SE). For those participants the Visit 3 questionnaire may be administered  
face-to-face. 
In addition, details (study-ID, name, sex, age, date of enrolment) of each participant will be 
documented in a study register, which will stored in a secure location by the site until 10 years after 
the end of the study unless local regulations or institutional policies require a longer retention period. 
The study register will be compared with the TB registers and clinic records to ascertain diagnostic 
results (such as smear results in the standard of care clinics), TB registration number and TB initiation 
dates. This will be documented on the study TB outcome worksheet. The completed worksheet will be 
retrieved at the end of the study, entered electronically and stored centrally. 
Data on number of contact attempts, contact information provided by trusted proxy, date and location 
of home visits will be documented on paper in free text. This information will not be entered and stored 
centrally. 
All paper forms (including consent form) will be stored in secure and locked cupboards with only 
authorised person having access to the forms. The electronic database will not include any names, but 
only study numbers. The OpenClinica Enterprise version 4.0 database will be secure, password 
protected and regularly backed-up. Only authorised people will have access to the database. 
Truenat TB assay results and error logs will be regularly backed-up on secure FIND servers. Interviews 
with users will be documented on paper-based questionnaires (user appraisal form). These will be 
entered into an electronic database. 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
 
 
10. STUDY ASSESSMENTS 
 
10.1 
Visit 1:  
Demographic and background assessments 
Following demographic and background variables will be collected according to the schedule of events 
table: 
 
Inclusion and exclusion criteria 
 
Written informed consent 
 
Demographic data: date of birth, gender 
 
Symptoms suggestive of TB 
 
TB treatment history 
 
HIV status (including antiretroviral therapy), diabetes 
 
Smoking and mining history 
 
Household assets 
 
Number of visits to a health care provider 
 
Health care provider first visited 
 
Costs of care 
 
Loss of income (SE questionnaire only) 
 
TB investigations and treatment 
All participants will be asked to submit a sputum sample for testing using Truenat platform/TB assays 
(intervention clinics) or standard of care testing (control clinics). TB treatment will be initiated by the 
clinic team not the study staff.  
 
 
10.2 
Visit 2 and 3 assessments 
The following efficacy variables will be assessed for evaluation of efficacy outcomes, at the time points 
indicated in the schedule of events table and documented on V2-D7 and V3-D60 CRFs. 
 
TB treatment initiation (at 7 and 60 days from enrolment) 
 
Microbiological confirmed TB up to 60 days from enrolment from Truenat assay result 
downloads and study registers 
 
 
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11. PATIENT ENROLMENT 
 
A total of 4200 patients will be enrolled at a minimum of 29 and a maximum of 37 clinics, coordinated 
by 4 sites in 2 countries, Tanzania and Mozambique. In Mozambique the aim is to recruit 2300 
participants (800-1000 recruited by CISM and 1300-1500 by INS). The total number of participants 
recruited in Mozambique may change dependent on recruitment rates in Tanzania. Tanzania aims to 
recruit 2100-2600 participants.  
Patients will be enrolled into the study only if they meet all the inclusion criteria and none of the 
exclusion criteria. The unit of randomisation is the clinic; hence patients accessing a certain clinic and 
consenting to the participate will receive investigations according to the arm into which the clinic was 
randomised. 
 
11.1 
Recruitment procedures 
All patients presenting with symptoms suggestive of pulmonary TB will be approached by the primary 
health care nurses and invited to participate in the study. Posters explaining the study will be placed 
in the clinics. All materials will be used only upon approval of the ethics committees and/or regulatory 
authorities relevant for this study. 
 
11.2 
Patient informed consent 
Patients presenting with signs and symptoms suggestive of pulmonary TB (as per the National 
Guidelines) will be invited to be screened for inclusion in the study. They will be given a patient 
information sheet and consent form (ICF) about the study and will be explained the anticipated 
benefits and the potential risks associated with the protocol procedures. The principal investigator or 
a person designated by the principal investigator will fully inform the patient. The language used will 
be as non-technical as possible and the patient will not unduly be influenced to participate in the study. 
Patients will be told that screening includes asking for symptoms suggestive of pulmonary TB and age. 
Patients will be told that agreeing to be screened does not mean that they have to join the study, and 
that participation in the study is voluntary. Patients will be informed that they will be free to withdraw 
from the study at any time, and a withdrawal will have no negative effects on them receiving standard 
care afterwards. 
Written (or witnessed oral informed consent) must be obtained from every patient prior to any 
procedures being done specifically for the study. 
For illiterate patients, study information is given in the presence of an impartial, literate witness, who 
will read the information sheet to the patient or will witness the complete reading of the information 
sheet to the patient. The patient will give consent by thumb printing the ICF and the witness states 
that free, informed consent has been given by his/her signature on the ICF. 
The signed original ICF will be kept in a locked cabinet at each research institute. A second original of 
the signed ICF will be given to the patient or to the patient’s legally acceptable representative. 
The ICF template will be provided to the investigator by the sponsor. If any modifications to the form 
are proposed by the site, the consent form must be submitted to the sponsor for approval prior to 
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submission to the ethics committee. The ICF will be revised whenever new important information 
becomes available and will undergo ethics committee review. All active patients must then sign 
additionally the revised form, after ethics approval was received. 
 
11.3 
Incentives and expenses 
Participants will not receive any incentives for the participation in the study. For participants who opt 
to be interviewed and reviewed at the clinics rather than at their homes for the Visit 3, visit transport 
costs will be reimbursed. The exact amount will be decided by each of the sites. 
 
11.4 
Exclusion of particular groups 
Children and adolescents aged <18 years will be excluded, because clinical presentation of TB disease 
differs between children and adults. 
 
11.5 
Participant withdrawal 
Participant may decide to withdraw from the study at any time and for any reason. The investigator 
may also withdraw a patient for any of the following reasons: 
 
Protocol deviation 
 
If, for any reason, the investigator concludes that continued participation in the study would 
not be in the participant’s best interest 
The investigator will also withdraw a patient upon request of the sponsor or if the study is terminated 
as a whole. Participants who decide to withdraw or who have been withdrawn from the study will not 
be replaced. After discontinuation of the study participant, the study team will not collect more 
information for the study but clinical care should continue in the health center. The study will not 
interfere with treatment; however, it will guarantee adequate referral and assist with screening in the 
event of loss of follow-up. 
 
12. STUDY PROCEDURES 
 
12.1 
Visit 1 Baseline visit 
Patients presenting with symptoms suggestive of pulmonary TB to one of the study clinics will be 
invited to be screened for inclusion in the study. Before any study-specific screening procedures will 
be performed, all patients will sign and date (or thumbprint) the latest version of the ICF. Illiterate 
participants will be encouraged to have a witness present. 
After informed consent has been obtained, the patient will receive a study number. The ICF will be 
labelled with the study number. A primary health care nurse or dedicated researcher staff will 
administer a questionnaire (V1-D1) and ask the patient about their contact details and the contact 
details of a trusted proxy (locator form). In addition, 5 to 10% participants per site will be invited to 
answer a socio-economic questionnaire about income, cost of care seeking, productivity losses, 
diagnostics and treatment (V1-D1-SE). For these participants a face-to-face interview may be 
conducted.  
Depending on the clinic, the patient will receive a diagnostic work-up according to the national 
algorithm (smear microscopy and/or off-site Xpert testing) or the study intervention (Truenat 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
platform/TB assays on site). Further diagnostic investigations and TB treatment initiation will be as 
clinically indicated. All clinical care and further investigations will be provided within the governmental 
health care service. Patient details (including name, sex, age, and study-ID) will be documented in a 
study register, which will remain at the clinic. All patients will receive a study card with their details 
(including name, sex, age and study number and enrolment date) to take home with them. They will 
be asked to show the card if they present to the clinic again. 
 
12.2 
Visit 2: Day 7 
All participants will be called by telephone 7 days after enrolment (between day 8 and day 21 after 
enrolment). Three attempts will be made to contact a participant by phone. If these attempts are 
unsuccessful the trusted proxy will be contacted to find out about the participant’s whereabouts and 
arrange for a return call by the participants or a home visit. A home visit will be conducted for those 
participants who cannot be reached by phone. 
The questionnaire administered by phone or face-face (V2-D7 CRF) will include questions about 
symptoms, whether TB was diagnosed (and by what means) and treatment started and if the 
participant had accessed another health care provider. 
 
12.3 
Visit 3: Day 60 
All participants will be called by telephone 60 days after enrolment (between day 61 and day 90 after 
enrolment). Three attempts will be made to contact a participant by phone. If these attempts are 
unsuccessful the trusted proxy will be contacted to find out about the participant’s whereabouts and 
arrange for a return call or a home visit. A home visit will be conducted for those participants who 
cannot be reached by phone.  
The questionnaire administered by phone or face-face (V3-D60) will include questions about 
symptoms, whether TB was diagnosed (and by what means) and treatment started and if the 
participant had accessed another health care provider and how often.  
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
 
 
13. STATISTICAL CONSIDERATIONS 
 
13.1 
Populations to be analyzed 
Intent-to treat (ITT) population: The ITT population will consist of all enrolled patients in the groups to 
which randomly assigned to intervention and controls. Patients with missing outcome data at days 7 
and 60 will be assumed to not have started treatment. 
 
Per-Protocol (PP) population: The PP population will consist of all patients who fulfil the protocol in 
the terms of eligibility, interventions, and outcome assessment without any major protocol deviation. 
 
The Statistical Analysis Plan (SAP) will define the criteria for the exclusion of patients from any of the 
above-mentioned analysis populations and will be finalized prior to database lock.  The SAP will also 
provide a detailed summary of the analysis methodology for each of the outcomes of the trial.  
 
13.2 
Design considerations 
Matched paired design and stratification have been considered as a study design. In fact, matched 
paired design can be regarded as an extreme form of stratification. Stratification involves the grouping 
of available clusters into strata that are expected to be similar in outcome. We have decided for 
stratification for the following reasons33: 
 
Fewer degrees in freedom are lost which is effective considering the relative low number of 
clusters per arm (10 .. 15). 
 
Adjustment for covariates via (generalized) linear models is possible 
 
Single missing clusters can be handled without losing a pair. 
 
13.3 
Randomization 
See section 9.5.2 
 
13.4 
Descriptive statistics 
Baseline characteristics, such as demographic and analytical data will be summarized using descriptive 
statistical methods. Continuous data will be summarized using the mean, the median, standard 
deviation, the range (minimum and maximum value). Categorical values will be summarized using 
frequency counts and percentages. 
 
13.5 
Analysis of endpoints 
Endpoints referring to proportion of patients (primary endpoint, further secondary endpoints acc. 
Table 1) will be compared across the two arms via generalized linear models using logit link function 
with intervention and stratum as fixed effect and cluster as random effect. Sensitivity analyses based 
on cluster-level summaries will be applied. Adjustment for other variables (such as HIV status) may be 
considered in sensitivity analyses and will be described in detail in the statistical analysis plan (SAP). 
Endpoints referring to time to event analyses will be described by Kaplan-Meier-curves by treatment 
and stratum. Depending on the hazard functions the analysis method will be chosen. Details will be 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
presented in the SAP. Table 1 describes the definition of endpoints and the way to calculation of 
referring proportions.  
 
Table 1: definition and derivation of endpoints 
Endpoint 
Numerator 
Denominator 
(applicable to 
proportions and rates) 
Data source 
Number and proportion 
of participants with 
microbiological 
confirmation starting TB 
treatment within 7 days 
Participants with 
microbiological confirmation 
starting TB treatment within 
7 days 
All participants 
Visit 2 telephone call (V2-D7) 
Register 
Study TB outcome worksheet 
Time to bacteriological 
confirmation 
Participants with 
microbiological confirmed 
TB 
Person Time at risk 
Visit 2 telephone call (V2-D7) 
Visit 3 telephone call (V3-D60)  
Study TB outcome worksheet 
Number and proportion 
of patients treated for TB 
with microbiological 
diagnosis 
Participants with 
microbiological confirmed 
TB and treated 
All participants 
treated for TB 
Visit 2 telephone call (V2-D7) 
Visit 3 telephone call (V3-D60)  
Study TB outcome worksheet 
Number and proportion of 
patients treated for TB 
with clinical diagnosis 
Participants with clinically 
diagnosed TB and treated 
All participants 
treated for TB 
Visit 2 telephone call (V2-D7) 
Visit 3 telephone call (V3-D60)  
Study TB outcome worksheet 
Number and proportion 
of participants with 
microbiological 
confirmation starting TB 
treatment within 60 days 
Participants with 
microbiological confirmation 
starting TB treatment within 
60 days 
All participants 
Visit 2 telephone call (V2-D7) 
Visit 3 telephone call (V3-D60) 
Study TB outcome worksheet 
Time to TB treatment 
initiation for those with 
microbiological 
confirmation 
Participants with 
microbiological confirmed 
TB starting treatment 
Person Time at risk 
Visit 2 telephone call (V2-D7) 
Visit 3 telephone call (V3-D60)  
Study TB outcome worksheet 
Time to TB treatment 
initiation and for all 
participants 
Participants starting TB 
treatment 
Person Time at risk 
Visit 2 telephone call (V2-D7) 
Visit 3 telephone call (V3-D60)  
Study TB outcome worksheet 
Number and proportion 
of participants with 
ongoing TB treatment 
outcome 
Ongoing TB treatment 
outcomes (on TB 
treatment at 60 days) 
Participants 
diagnosed with TB 
Participants 
diagnosed with TB 
clinically 
Participants 
diagnosed with TB 
microbiologically 
Visit 2 telephone call (V2-D7) 
Visit 3 telephone call (V3-D60)  
Study TB outcome worksheet  
TB treatment register 
Cost of diagnosis and 
treatment 
Total cost to 
participants (among 
participants who 
respond to the costing 
survey) 
Not applicable 
Visit 1 extended questionnaire 
(V1-D1-SE) 
 
13.6 
Other analyses 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
Other analysis will include 
i) comparison of proportions using similar methodology as for proportion-related endpoints: 
 
initiating TB treatment with microbiologically diagnosed (or all) TB at 60  
ii) time to TB treatment initiation (adjusted for strata) across arms 
 
for microbiologically confirmed TB cases 
 
for clinical diagnosed TB case 
 
for all TB cases 
Analysis of cost, number of health care visits and symptoms will be done either by comparing 
proportions or mean (adjusted for strata). 
 
13.7 
Interim analysis 
For this study no formal interim analysis is planned. 
 
13.8 
Sample size determination 
For the purpose of sample size estimation, a matched design is regarded which is known to have 
a similar power in the range of number of clusters per treatment arm similar to this study 
(~15,30). Sample size calculation were based on 972 scenarios using assumptions for 
 
TB prevalence: 12%, 16%, 20% 
 
Sensitivity for intervention group: 89% 
 
Sensitivity for control group: 70%, 75%, 80% 
 
Diagnostic LTFU intervention arm: 2% 
 
Diagnostic LTFU control arm: 5%, 10% 
 
Pre-treatment LTFU1 intervention arm: 8%, 10%, 12% 
 
Pre-treatment LTFU control arm: 16%, 20%, 24%31 
 
Cluster size CS 100, 125, 150, 200 (cluster sizes are regarded as average values of a distribution 
of cluster sizes). 
 
Within pair coefficient variation 𝐶𝑉𝑚: 0.25 according to recommendation in case of 
missing information given in 
 
Alpha-level  = 0.05 
 
Power: 80% ( = 0.2) 
 
From the prevalence, sensitivity and LTFUs in the diagnostics the proportions p of treated patients is 
derived (𝑝 = 𝑝𝑟𝑒𝑣 ∙ 𝑠𝑒𝑛𝑠 ∙ (1 ― 𝐿𝑇𝐹𝑈𝑑𝑖𝑎𝑔) ∙ (1 ― 𝐿𝑇𝐹𝑈𝑝𝑟𝑒 ― 𝑡ℎ𝑒𝑟) for each of intervention and control 
arm ( 𝑝𝑖, 𝑝𝑐). 
The number of cluster pairs 𝑁𝑐𝑝 is calculated according to the following formula [Hayes RJ, Moulton LH 
2017]: 
𝑁𝑐𝑝= 𝐴+ (𝑧𝛼/2 + 𝑧𝛽)
2 𝑝𝑖(1 −𝑝𝑖)/𝐶𝑆+ 𝑝𝑐(1 −𝑝𝑐)/𝐶𝑆+ 𝐶𝑉𝑚
2(𝑝𝑖2 + 𝑝𝑐2)
(𝑝𝑖−𝑝𝑐)2
 
whereby the result is rounded up to the next whole number, with A = 1 [Hayes RJ, Moulton 2017]29. 
Note that Software PASS [PASS 2020] uses A=2, [Hayes and Bennett 1999]30 uses A=0. 
z = quantile of normal distribution. 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
One should note that smaller cluster sizes (which would result in more clusters) are advantageous in 
terms of total number of patients to be recruited. Thus, the scenario has to be selected taking in into 
account number of patients on the one hand and efforts to recruit and organise sites on the other 
hand. 
 
Following scenarios have been selected according to feasibility and mid-range choice of the 
ranges presented above: 
 
 
Cluster size 
Prevalence 
Sensitivity control 
diagn. LTFU control 
(diagn. LTFU for intervention: 0.02) 
pre-trt. LTFU intervention 
pre-trt. LTFU control 
success proportion intervention 
success proportion control 
number of cluster pairs 
Number of clusters 
Number of patients 
100 
16% 
70% 
10% 
10% 
20% 
13% 
8% 
14 
28 
2800 
100 
12% 
70% 
10% 
8% 
20% 
10% 
6% 
15 
30 
3000 
100 
12% 
70% 
10% 
10% 
20% 
9% 
6% 
17 
34 
3400 
100 
12% 
70% 
10% 
12% 
20% 
9% 
6% 
18 
36 
3600 
150 
12% 
70% 
10% 
10% 
20% 
9% 
6% 
13 
26 
3900 
150 
16% 
70% 
5% 
10% 
20% 
13% 
9% 
14 
28 
4200 
150 
16% 
70% 
10% 
10% 
20% 
13% 
8% 
12 
24 
3600 
200 
12% 
70% 
10% 
10% 
20% 
9% 
6% 
12 
24 
4800 
200 
16% 
70% 
5% 
10% 
20% 
13% 
9% 
13 
26 
5200 
200 
16% 
75% 
10% 
10% 
20% 
13% 
9% 
14 
28 
5600 
Table 2: selected scenarios. Colours vary with cluster size and prevalence. Red: final scenario. 
 
Applying an alpha-level of 0.05, a power of 80%, 12% prevalence, diagnostic LTFU-rates of 10% 
(control), 10% (pre-treatment intervention), 20% (pre-treatment control), a cluster size of 150 and a 
within-pair coefficient of variation (default value 0.2529), the results bring a total of 13 cluster pairs (3900 
patients). In order to address uncertainty, 1 additional cluster pair will be added, bringing the total to 
14 cluster-pairs (28 clinics, 4200 patients) to be included in the trial. If based on what will be observed 
in the initial setup period, smaller than average cluster sizes are expected, more sites will need to be 
included in the trial in order to match the total sample size. 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
 
14. DATA MANAGEMENT 
 
14.1 
Data management plan 
A data management plan will be drafted and agreed upon before the start of enrolment. 
 
14.2 
Data collection 
The investigator agrees to maintain accurate source data and CRFs. For each patient screened a CRF 
will be completed, even if the patient drops out at any time point during the study. All information 
from a telephone interview or a performed visit must be entered in the CRF. 
 
CRFs should be completed legibly with black ballpoint pen 
 
CRF information should be complete 
 
Corrections should be made such that the original information is not obscured, i.e., by 
striking through the incorrect entry with a single line and the corrected information should 
be entered next to the deleted item. Corrections should be initialled and dated by the person 
making the correction 
 
Each completed CRF must be reviewed, signed, and dated by the investigator or a 
responsible person the investigator has delegated this task to in a timely manner. The 
complete CRF will be collected by study monitors as soon as practical after completion. 
 
14.3 
Source documents 
The investigator agrees to maintain accurate source documents as part of the case histories and 
permits direct access for domestic and foreign regulatory authorities, sponsors, monitors and auditors. 
 
The following data will be recorded directly into the CRF and will be considered source data: 
 
Date of enrolment or interview 
 
Sex 
 
Age 
 
Symptoms 
 
Medical history 
 
TB diagnostic status 
 
TB treatment status 
 
Health seeking 
 
Symptoms 
 
Costs 
 
Vital status 
 
14.4 
Data entry 
Timely data entry is of utmost importance for this trial for the following reasons: 
 
To closely monitor patient recruitment and ensure recruitment is on target given the tight 
timelines 
 
To ensure Visit 2 follow-up calls (which directly inform the primary outcome) are conducted 
within 8-21 days post recruitment 
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Protocol short title: TB-CAPT CORE Truenat trial 
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Protocol Version: 4.0 
 
 
 
 
The investigator agrees to timely entry of all V1-D1, V2-D7 and V3-M2 within 7 days of data collection.  
 
14.5 
Data handling and record keeping 
Records and documents, including signed ICFs, pertaining to the conduct of this trial must be retained by 
the investigator for 10 years after trial completion unless local regulations or institutional policies require 
a longer retention period. No records may be destroyed during the retention period without the written 
approval of FIND. No records may be transferred to another location or party without written notification 
to FIND.  
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
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15. MONITORING AND QUALITY ASSURANCE 
 
15.1 
Study monitoring 
One or more monitors will be assigned to the study. The monitor, as a representative of the sponsor, 
has the obligation to follow the study closely. The monitor will visit the site at regular intervals and will 
be in contact by phone and written communication, as required. 
 
Site investigators and designated study personnel will allow the monitors to inspect study documents, 
clinic records as well as site facilities, as required. All aspects of the study will be carefully monitored 
in order to ensure compliance with Good Clinical Practice and all applicable regulatory guidelines. The 
monitor will be responsible for verification of 
 
 
adequacy of study personnel’s qualifications as well as facilities 
 
the accuracy and completeness of the CRF entries, source documents and other study- 
related records 
 
appropriate IMP storage, usage, and accountability 
 
informed consent procedures and patient eligibility 
 
maintenance of the essential documents 
 
all other aspects of the study relating to protection of the rights and well-being of 
patients, accuracy of study data and adherence to the protocol 
 
The study database will only be closed after data has been verified by the monitor and the sponsor, 
and all queries issued through data cleaning activities have been completed. 
 
15.2 
Inspection of record 
The investigator will allow the sponsor, the sponsor’s representatives, regulatory agencies and ethics 
committees access to all study records, if requested. The investigator will promptly notify the sponsor 
of any inspections scheduled by regulatory authorities or ethics committees and promptly forward 
copies of any inspection reports received to the sponsor. 
 
15.3 
Record retention 
The sponsor will keep essential study documents (including CRFs) for at least 10 years after completion 
or discontinuation of the study. 
 
15.4 
Confidentiality of personal data 
All patient records, lab specimen etc. will be identified in a manner to maintain patient confidentiality 
and will be kept in a secure storage area with limited access. Each participant will be assigned a 
pseudonymous study number. No data that could identify the patient other than this identification 
number (sex and date of birth) will appear on the CRFs. 
Data of study patients will only be used as defined in the ICF and in line with applicable data privacy 
regulations. Accordingly, patient records may be reviewed by inspectors of regulatory authorities or 
ethics committees, study monitors and auditors, who ensure the quality of the study. 
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An individual’s study data will not be released without the written agreement of the patient (or their 
legal guardian), except as necessary for monitoring and auditing by the sponsor or its representative, 
regulatory authorities, or ethics committees, or in case of medical emergencies when written consent 
cannot be obtained, as deemed in the participant’s best interest by the investigator. 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
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16. USER PREFERENCES (Qualitative sub-study 
assessing usability, feasibility, and acceptability) 
 
Incorporating patients’ preferences in the development of a POC strategy for TB diagnosis using the 
Truenat platform/TB assays may facilitate its implementation and improve health outcomes. Aside 
from evaluating the test accuracy, it is important to understand experiences and preferences of those 
who will use the technology. Qualitative methods are ideal for making sense of user experiences with 
and perspectives on diagnostic tools within “real-world” situations. Furthermore, an assessment of 
values and preferences, acceptability and ease-of-use is an integral part of the WHO evaluation of 
novel diagnostic tests. We intend to explore these aspects alongside the prospective study for the 
Truenat platform/TB assays. 
 
16.1  Objectives 
Primary 
objectives 
To investigate user perspectives on the Truenat platform/TB assays (including perspectives 
of end-users (such as patients), but also of professional users such as laboratory 
technicians, clinicians, nurses, and decision-makers) for use as a diagnostic test for 
outpatients presenting with symptoms suggestive of pulmonary TB. 
To investigate and compare experiences and challenges with diagnostic testing for TB in 
patients using the different diagnostic approaches (Xpert® MTB/RIF (Ultra), microscopy, 
culture). 
To understand feasibility and preferences with regard to diagnosing TB and how the 
Truenat platform /TB assays change these. 
To assess the usability and acceptability of the Truenat platform/TB assays in the intended 
users.  
Secondary 
objectives 
To explore potential implications for health equity of this POC test (for instance by cutting 
diagnostic delay, reducing loss to follow up, cost concerns, increased accessibility, linkage 
to care). 
 
16.2 General Design and participants 
We will use a qualitative approach using semi-structured interviews with patients, professional users 
(laboratory staff, nurses, clinicians) and decision makers. In addition, to assess the usability of the 
Truenat platform/TB assays, we will conduct direct observations of the testing procedures and perform 
Ease-of-use and usability surveys. 
Semi-structured interviews with professional users (healthcare and laboratory staff, study staff), decision 
makers and adult patients seeking diagnosis for TB (involved in the CORE trial):  
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Protocol short title: TB-CAPT CORE Truenat trial 
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To gain insights from various professional users, we will include 3-5 healthcare workers from each 
user group (including nurses, clinicians and laboratory technicians involved in routine care 
provision as well as study staff involved in the study) at each site, or until saturation is reached. 
Separately, we will include interviews with 3 TB and HIV programme officers (decision makers), 
which will allow us to gain insights in the perspective of decision makers in the program at each 
site.  In total, we seek to interview approximately 10-15 health care workers and decision makers 
per country. 
To gain end-user perspectives, we will invite 10-12 participants from each coordinating site 
(approx. 20-24 per country) for an interview, either when being enrolled in the study or later 
through the follow-up mechanisms that are part of the study. We will aim to obtain an equal 
number of patients who tested positive or negative, as well as from the intervention and control 
clinics. 
Observations at study sites and surveys (Ease-of-Use and System Usability Scale):  
At the intervention clinics, research staff will conduct a standardized training for the Truenat 
platform /TB assays. After completing the training, health workers will be asked to perform 
specimen collection and/or testing under direct observation up to 4 patients enrolled in the 
study. Namely, research staff will observe them while performing the test and will record the 
time spent on specimen collection and/or testing, as well as any errors or failures that occur. 
They will also ask participants to provide general comments on device usability. 
Following direct observation, participants will also be asked to complete a survey. The survey will 
include the System Usability Scale (SUS), a 10-item questionnaire on a 5-point Likert scale, to 
rate the usability of the test32,33, and additional questions for health workers to rate the 
acceptability, and an Ease-of-Use questionnaire developed especially for the Truenat platform 
/TB assays. 
Ten eligible health workers (operators of the test) preferably from the intervention clinics will be 
invited to participate in the direct observations and surveys per country. Health workers will be 
purposively sampled to reflect the intended setting of use for the Truenat platform /TB assays. 
16.3  Sample size and sampling 
Sample size determination in qualitative research rests on maximizing potential for “saturation” (when 
new interviews do not meaningfully add to codes and themes already represented in the previously 
collected data).  Based on previous experience on assessing user preferences, and literature in sampling 
for qualitative research34, we expect to reach saturation for thematic analysis of patients (20-24/country) 
and professional users, while an exploratory analysis of the decision makers perspectives (overall 
professionals: 10-15/country, although only 3/country are expected to be decision makers).  
 
Participants will be purposively sampled35, with a maximum variation approach36, which seeks to capture 
the maximum variation for a defined spectrum to identify information-rich cases.  A sampling frame, with 
potential participants matching the eligibility and purposive sampling criteria, will be created based on 
demographic and trial data. Patients will then be invited to participate by the local study staff.  
16.4  Inclusion & Exclusion Criteria 
Inclusion criteria for semi-structured interviews: 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
- 
Adult aged ≥ 18 years old 
- 
Either: 
o (1) Routine healthcare worker participating in the CORE trial, or  
o (2) Patient tested or to be tested for TB as part of the CORE study, or  
o (3) Decision maker involved with implementation of novel tests at the local, national 
and/or regional level. 
 
Inclusion criteria for direct observations and surveys (Ease-of-Use and SUS): 
- 
Adult aged ≥ 18 years old 
- 
Involved in routine TB testing (collecting specimens for or performing TB tests). 
 
Exclusion criteria (all): unable or unwilling to provide consent  
Exclusion criteria (semi-structured interviews): does not agree to allow audio recording of interviews 
 
16.5 Topic guide, data management (protection) and analysis 
An interview topic guide to support the qualitative data collection will be developed for the study. 
Data will be stored in a secure way accessible only to the researchers involved: password encrypted 
(digital) and in a locked office in a locked fireproof cabinet (hard copies/notebooks). All the 
information collected for this study will be kept strictly confidential by identifying the participants 
with a unique code (or study ID) to which only the study investigators have access. Only de-identified 
transcripts, survey answers and notes will be kept on a password protected server or a locked 
cabinet for 10 years following Proposals for Safeguarding Good Scientific Practice (version 2013) of 
the German Research Foundation (or longer if local regulations require). Audio-files will be 
destroyed after transcription. Information may only be passed on to other institutions involved in 
the study if they are pseudonymized for data protection reasons and after signing Data Transfer 
Agreement between collaborating institutions. The third parties will not have access to the data. 
Personal information and names will not be revealed at publication and all personal data will be 
anonymized accordingly to the research purpose. 
 
Thematic analysis will be conducted for the qualitative data using NVivo software. We will use a pre-
defined coding framework, which will be updated as the analysis is conducted, to reflect emerging 
themes. Reporting will follow guidelines for qualitative studies (Consolidated criteria for reporting 
qualitative research (COREQ), 2007).  
Descriptive analysis will be done for the survey data (Ease of Use and SUS).    
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
 
 
17. ETHICAL CONSIDERATIONS 
 
17.1 Risks and benefits  
As the Truenat platform and TB assays are WHO approved diagnostics for smear replacement, and 
no additional study specific samples are being collected, there are no specific ethical 
considerations and risks for this study. Participants accessing the intervention clinic will receive 
timely diagnosis with a CE-marked WHO endorsed diagnostic (the Truenat platform). Diagnostic 
testing will be closely monitored and all staff members performing the testing will be adequately 
trained. 
 
17.2 Safety and incident reporting 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an adverse events (AE) or severe adverse events (SAE) 
and remain responsible for following up and reporting AEs that are serious, considered related to the 
trial intervention or trial procedures, or that caused the participant to discontinue the trial. 
Given that this is a trial of near patient testing of a WHO endorsed assay (the Truenat platform) the 
probability of an AE or SAE occurring to a trial participant to be associated with the investigational 
products is extremely low. 
 
17.3 Basic principles 
This study will be performed in accordance with the study protocol, the current ICH- Guideline for GCP 
E6 (R2) (2016)/WHO Guidelines for GCP/WHO Handbook for Good Clinical Research Practice 
/Declaration of Helsinki/CIOMS International Ethical Guidelines for Biomedical Research Involving 
Human Subjects as well as any other applicable national and other regulatory guidelines. 
 
17.4 Involvement of ethics committees and regulatory authorities 
The protocol and the informed consent document to be used in this study must be submitted to the 
responsible investigators’ ethics committees and regulatory authorities, and also to the sponsor’s EC 
for approval. Written documentation of approval of the project and all relevant documents must be 
provided to the sponsor before starting the study. 
The investigator will promptly report to the EC deviations from the protocol and all unanticipated risks 
to human subjects or others, and will not make changes in the defined research without EC approval, 
except where necessary to eliminate apparent immediate hazards to human subjects. 
 
17.5 Protocol amendment policy 
Any substantial change to the protocol will be affected by means of a protocol amendment and has to 
be submitted to ethics committees and regulatory authorities. No amendment will be implemented 
until approved and signed by all required parties. Exceptions to this are when the investigator considers 
that the subject’s safety is compromised. 
Protocol amendments detailing minor administrative changes should be agreed in advance with the 
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Protocol short title: TB-CAPT CORE Truenat trial 
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Protocol Version: 4.0 
 
 
 
 
sponsor and submitted by the investigator to ethics committees and regulatory authorities for 
notification purposes as appropriate. 
 
17.6 Discontinuation criteria 
FIND reserves the right to close the trial site or terminate the trial at any time for any reason at its sole 
discretion. Investigational sites will be closed upon trial completion. A trial site is considered closed 
when all required documents and trial supplies have been collected. The investigator may initiate trial- 
site closure at any time, provided there is reasonable cause and sufficient notice is given in advance of 
the intended termination. Reasons for early closure of a trial site by FIND are described in the 
contractual agreement. 
 
17.7 Falsification of data 
Any proven evidence of falsification of data will be dealt with in accordance with the policy of the 
sponsor and appropriate action will be taken. 
 
 
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Protocol short title: TB-CAPT CORE Truenat trial 
Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
 
 
18. ADMINISTRATIVE CONSIDERATIONS 
 
18.1 Financing 
The study sponsor is the Foundation of Innovative Diagnostics. The study is funded by the European 
and Developing Countries Clinical Trials Partnership (EDCTP). 
 
18.2 Study registration 
Before study start, the study will be registered in a WHO recognised study registry (clinicaltrials.gov). 
 
18.3 Patient insurance and compensation 
The sponsor certifies that it has obtained or will obtain clinical study insurance in line with the 
requirements in each country prior to study start and will provide an associated certificate upon 
request. The insurance does not relieve the investigators of the obligation to maintain their own 
liability insurance as required by applicable law. The sponsor does not assume any obligation for the 
medical treatment of other injuries and illnesses. 
 
18.4 Training for staff involved in the study 
During the initiation visit the monitor will ensure all involved site personnel is trained on all procedures 
relevant for their study responsibilities. This will include weekly monitoring visits to each of the clinics 
to collect CRFs, administration of V1-D1, V2-D7 and V3-M2 CRFs. 
Training and supervision of primary health care nurses on study procedures and microscopists will be 
performed separately and documented in the electronic trial master file. The site personnel will be 
responsible to monitor the primary health care nurses and microscopists and re-train as necessary. 
 
18.5 Publication policy 
A dedicated TB-CAPT publication policy has been developed.  In brief, after completion of the study, 
the data will be considered for presenting at a scientific conference or for publication in a scientific 
journal. The sponsor will be responsible for these activities and will collaborate with the Scientific 
Advisory Board to determine how the manuscript is written and edited, the number and order of 
authors, the journal to which it will be submitted and other related issues. 
 
The results of the study will be published independent of the outcome – positive or negative - of the 
study. 
 
Under certain circumstances, i.e., when the publication of particular findings (of an epidemiological, 
sociological or genetics study) may present a risk to the interest of a community or population or a 
racially or ethnically defined group of people, it may be considered inappropriate to publish findings. 
 
 
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Protocol Number: TB041-3/1 -MZ 
Protocol Version: 4.0 
 
 
 
 
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