Two-month Regimens Using Novel Combinations to Augment Treatment Effectiveness for Drug-sensitive Tuberculosis (TRUNCATE-TB)

August 9, 2023 updated by: University College, London

The current standard management strategy for drug-sensitive pulmonary tuberculosis (TB) is to treat with multiple drugs for 6 months, although patients often fail to adhere to the long treatment, leading to poor clinical outcomes including drug resistance, which is expensive and difficult to treat.

The TRUNCATE-TB trial evaluates an alternative strategy (the TRUNCATE-TB Management Strategy) comprising treatment for 2 months (8 weeks, extended to 12 weeks if inadequate clinical response) with a regimen predicted to have enhanced sterilising activity ("boosted regimen") and monitoring closely after treatment cessation. Those who relapse (predicted to be always drug sensitive and likely to occur early) will be retreated with a standard 6 month regimen.

The trial is a randomized, open-label, multi-arm, multi-stage (MAMS) trial to test the hypothesis that the TRUNCATE-TB Management Strategy is non-inferior to the standard management strategy in terms of longer-term outcomes (clinical status at 96 weeks). If non-inferiority is demonstrated then the advantages/disadvantages of implementing the strategy will be explored in secondary outcomes (from patient and programme perspective).

The trial will evaluate the TRUNCATE-TB Management Strategy with 4 potential boosted regimens (180 per arm, total 900 with the standard TB management strategy arm). The boosted regimens include new drugs (licensed drugs, repurposed from other indications) and optimized doses of standard drugs, selected based on consideration of maximal sterilising effect, absence of drug-drug interactions, as well as safety and tolerability over a period of 2 months

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
675

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Christopher Cousins, Project Leader
  • Phone Number: 65 6601 5371
  • Email: mdccdc@nus.edu.sg

Study Contact Backup

Study Locations

  • India
      • New Delhi, India
        • National Institute of TB and Respiratory Diseases
  • Indonesia
      • Bandung, Indonesia
        • Universitas Padjadjaran
      • Jakarta, Indonesia
        • Persahbahatan Hospital
      • Makassar, Indonesia
        • Wahidin Sudirohusodo Hospital
      • Malang, Indonesia
        • Saiful Anwar Hospital
      • Surabaya, Indonesia
        • Soetomo General Hospital
  • Philippines
      • Cebu, Philippines
        • Perpetual Succour Hospital
      • Manila, Philippines
        • De La Salle Health Sciences Institute
      • Manila, Philippines
        • Lung Center Philippines
      • Manila, Philippines
        • Philippines Tuberculosis Society Incorporated (PTSI)
      • Manila, Philippines
        • Tropical Disease Foundation
      • Quezon City, Philippines
        • Quezon Institute
  • Singapore
      • Singapore, Singapore
        • National University Hospital
  • Thailand
      • Bangkok, Thailand
        • King Chulalongkorn Memorial Hospital
      • Nonthaburi, Thailand
        • Central Chest Institute of Thailand
  • Uganda
      • Kampala, Uganda
        • Infectious Diseases Institute
      • Kampala, Uganda
        • Joint Clinical Research Centre
      • Mbarara, Uganda
        • Joint Clinical Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 18 to 65 years
  2. Clinical symptoms consistent with pulmonary TB and/or evidence of pulmonary TB on chest X-ray (CXR)
  3. Sputum GeneXpert test positive
  4. Willing to comply with the study visits and procedures
  5. Resident at a fixed address
  6. Willing to have directly observed therapy
  7. Willing and able to provide written informed consent

Exclusion Criteria:

  1. Taken more than 10 daily doses of standard anti-TB medication or fluoroquinolones during the 3 months prior to randomisation
  2. Previous active TB disease for which treatment was given prior to the current episode
  3. Known or suspected extra-pulmonary TB
  4. Severe clinical pulmonary TB
  5. Sputum smear 3+ on microscopy*
  6. Cavity size > 4cm on screening CXR*
  7. Presence of rifampicin resistance on GeneXpert test
  8. Poorly-controlled diabetes that, in the opinion of the investigator, is unlikely to be controlled with available management strategies
  9. Active malignancy requiring systemic chemotherapy or radiotherapy
  10. Known Hepatitis B surface antigen positive and/or HCV antibody positive, unless liver function tests consistently within normal range for at least 2 years
  11. History of myocardial infarction, congestive cardiac failure, cardiac arrhythmias or any known congenital cardiac problems
  12. History of severe chronic lung disease with symptom score of ≥3 on MRC breathlessness scale
  13. History of seizures
  14. Current tendinitis or history of tendinopathy associated with fluoroquinolone use
  15. Symptomatic peripheral neuropathy causing greater than minimal interference with usual social and functional activities
  16. Current alcohol or drug abuse
  17. Women who are currently pregnant or breast-feeding
  18. Women of childbearing potential unwilling or unable to use appropriate effective contraception for the first 6 months of the trial
  19. Known allergy to one or more of the study drugs
  20. Taking a concomitant medication that has a known or predicted interaction with any of the study drugs to which the patient might be randomised, or is known to prolong the QTc interval
  21. Taking any immunosuppressive drugs or use of systemic corticosteroids for more than 2 weeks prior to screening
  22. Colour blindness detected by Ishihara test

23.12-lead ECG at screening shows QTc greater than 450ms and/or any other clinically-significant abnormality such as arrhythmia or ischaemia

24.Any of the following laboratory parameters at screening:

  • Absolute neutrophil <1000 cells/mL, haemoglobin <7.0 g/dL, OR platelet count <50,000 cells/mm3
  • Creatinine clearance of <60ml/min (calculated using Cockcroft-Gault equation)
  • ALT greater than 3 times the upper limit of normal

  • Uncorrected serum potassium <3.5 mmol/L

    25.HIV antibody positive at screening*

    26.Any other significant condition (e.g. psychiatric illness, chronic diarrhoeal disease), that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial or lead to poor compliance with study visits and protocol requirements

    27.Participation in other clinical intervention trial or research protocol

Note: *Criteria may be modified in later stages of the trial

-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard TB Management Strategy
Standard combination treatment for pulmonary TB of 8 weeks rifampicin, isoniazid, pyrazinamide, ethambutol, then 16 weeks rifampicin, isoniazid only
Drug: Rifampicin
10mg/kg
Drug: Isoniazid
5mg/kg
Drug: Pyrazinamide
25mg/kg
Drug: Ethambutol
15mg/kg
Drug: Rifampicin
35mg/kg
Experimental: TRUNCATE-TB Management Strategy using Regimen B

TRUNCATE-TB Management Strategy: 8 weeks* of initial treatment using Regimen B; close monitoring after treatment completion; treatment of relapse with 24 weeks of standard treatment.

*If persistent symptoms and positive smear at week 8, extend to 12 weeks of treatment using Regimen B; if persistent symptoms and positive smear at week 12, switch to standard treatment regimen and extend to 24 weeks of treatment.

Regimen B: Rifampicin (35mg/kg), isoniazid, pyrazinamide, ethambutol, linezolid
Drug: Rifampicin
10mg/kg
Drug: Isoniazid
5mg/kg
Drug: Pyrazinamide
25mg/kg
Drug: Ethambutol
15mg/kg
Drug: Rifampicin
35mg/kg
Drug: Linezolid
600mg
Experimental: TRUNCATE-TB Management Strategy using Regimen C

TRUNCATE-TB Management Strategy as described above, using Regimen C in place of B.

Regimen C: Rifampicin (35mg/kg), isoniazid, pyrazinamide, ethambutol, clofazimine
Drug: Rifampicin
10mg/kg
Drug: Isoniazid
5mg/kg
Drug: Pyrazinamide
25mg/kg
Drug: Ethambutol
15mg/kg
Drug: Rifampicin
35mg/kg
Drug: Clofazimine
200mg
Experimental: TRUNCATE-TB Management Strategy using Regimen D

TRUNCATE-TB Management Strategy as described above, using Regimen D in place of B.

Regimen D: Rifapentine, isoniazid, pyrazinamide, linezolid, levofloxacin
Drug: Isoniazid
5mg/kg
Drug: Pyrazinamide
25mg/kg
Drug: Linezolid
600mg
Drug: Rifapentine
1200mg
Drug: Levofloxacin
1000mg
Experimental: TRUNCATE-TB Management Strategy using Regimen E

TRUNCATE-TB Management Strategy as described above, using Regimen E in place of B.

Regimen E: Isoniazid, pyrazinamide, ethambutol, linezolid, bedaquiline
Drug: Isoniazid
5mg/kg
Drug: Pyrazinamide
25mg/kg
Drug: Ethambutol
15mg/kg
Drug: Linezolid
600mg
Drug: Bedaquiline
400mg once daily for 2 weeks then 200mg 3x a week

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Unsatisfactory clinical outcome at week 96 after randomisation
Time Frame: 96 weeks
As defined by ongoing requirement for TB treatment at week 96 OR ongoing TB disease activity at week 96 (clinical, microbiological and/or imaging evidence) OR death before week 96
96 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Acceptability of the strategy using trial-specific questionnaire
Time Frame: 96 weeks
7-item trial-specific questionnaire
96 weeks
Total days on TB drug treatment
Time Frame: 96 weeks
96 weeks
Time off work or study due to illness/treatment
Time Frame: 96 weeks
96 weeks
Total Quality of life using MOS-HIV questionnaire
Time Frame: 96 weeks
MOS-HIV questionnaire
96 weeks
Respiratory disability at week 96
Time Frame: 96 weeks
96 weeks
Total Grade 3 or 4 clinical adverse events
Time Frame: 96 weeks
96 weeks
Total serious adverse events
Time Frame: 96 weeks
96 weeks
Death
Time Frame: 96 weeks
96 weeks
Adherence to TB medication
Time Frame: Either during first 8 weeks or at any time during period when TB treatment is prescribed
Either during first 8 weeks or at any time during period when TB treatment is prescribed
Treatment default
Time Frame: Either during first 8 weeks or at any time during period when TB treatment is prescribed
Either during first 8 weeks or at any time during period when TB treatment is prescribed
Acquired drug resistance by week 96
Time Frame: 96 weeks
96 weeks
Community transmission risk
Time Frame: 96 weeks
96 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University College, London

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National University Hospital, Singapore
Singapore Clinical Research Institute (SCRI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Nicholas Paton, National University Hospital, Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 21, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 20, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 20, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 12, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 21, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 22, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 9, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TRUNCATE-TB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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