Two-month Regimens Using Novel Combinations to Augment Treatment Effectiveness for Drug-sensitive Tuberculosis (TRUNCATE-TB)
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ClinicalTrials.gov Identifier: NCT03474198 |
Recruitment Status : Unknown
Verified April 2019 by University College, London.
Recruitment status was: Recruiting
First Posted : March 22, 2018
Last Update Posted : April 19, 2019
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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
Condition or disease | Intervention/treatment | Phase |
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Tuberculosis, Pulmonary | Drug: Rifampicin Drug: Isoniazid Drug: Pyrazinamide Drug: Ethambutol Drug: Linezolid Drug: Clofazimine Drug: Rifapentine Drug: Levofloxacin Drug: Bedaquiline | Phase 2 Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 900 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | This study uses a multi-arm, multi-stage (MAMS) parallel study design |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Two-month Regimens Using Novel Combinations to Augment Treatment Effectiveness for Drug-sensitive Tuberculosis |
Actual Study Start Date : | March 21, 2018 |
Estimated Primary Completion Date : | March 12, 2022 |
Estimated Study Completion Date : | March 12, 2022 |

Arm | Intervention/treatment |
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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
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Drug: Rifampicin
10mg/kg Drug: Isoniazid 5mg/kg Drug: Pyrazinamide 25mg/kg Drug: Ethambutol 15mg/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: Isoniazid
5mg/kg Drug: Pyrazinamide 25mg/kg Drug: Ethambutol 15mg/kg Drug: Linezolid 600mg Drug: Rifampicin 35mg/kg |
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: Isoniazid
5mg/kg Drug: Pyrazinamide 25mg/kg Drug: Ethambutol 15mg/kg Drug: Clofazimine 200mg Drug: Rifampicin 35mg/kg |
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 |
- 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
- Acceptability of the strategy using trial-specific questionnaire [ Time Frame: 96 weeks ]7-item trial-specific questionnaire
- Total days on TB drug treatment [ Time Frame: 96 weeks ]
- Time off work or study due to illness/treatment [ Time Frame: 96 weeks ]
- Total Quality of life using MOS-HIV questionnaire [ Time Frame: 96 weeks ]MOS-HIV questionnaire
- Respiratory disability at week 96 [ Time Frame: 96 weeks ]
- Total Grade 3 or 4 clinical adverse events [ Time Frame: 96 weeks ]
- Total serious adverse events [ Time Frame: 96 weeks ]
- Death [ Time Frame: 96 weeks ]
- Adherence to TB medication [ Time Frame: 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 ]
- Acquired drug resistance by week 96 [ Time Frame: 96 weeks ]
- Community transmission risk [ Time Frame: 96 weeks ]

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Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age 18 to 65 years
- Clinical symptoms consistent with pulmonary TB and/or evidence of pulmonary TB on chest X-ray (CXR)
- Sputum GeneXpert test positive
- Willing to comply with the study visits and procedures
- Resident at a fixed address
- Willing to have directly observed therapy
- Willing and able to provide written informed consent
Exclusion Criteria:
- Taken more than 10 daily doses of standard anti-TB medication or fluoroquinolones during the 3 months prior to randomisation
- Previous active TB disease for which treatment was given prior to the current episode
- Known or suspected extra-pulmonary TB
- Severe clinical pulmonary TB
- Sputum smear 3+ on microscopy*
- Cavity size > 4cm on screening CXR*
- Presence of rifampicin resistance on GeneXpert test
- Poorly-controlled diabetes that, in the opinion of the investigator, is unlikely to be controlled with available management strategies
- Active malignancy requiring systemic chemotherapy or radiotherapy
- Known Hepatitis B surface antigen positive and/or HCV antibody positive, unless liver function tests consistently within normal range for at least 2 years
- History of myocardial infarction, congestive cardiac failure, cardiac arrhythmias or any known congenital cardiac problems
- History of severe chronic lung disease with symptom score of ≥3 on MRC breathlessness scale
- History of seizures
- Current tendinitis or history of tendinopathy associated with fluoroquinolone use
- Symptomatic peripheral neuropathy causing greater than minimal interference with usual social and functional activities
- Current alcohol or drug abuse
- Women who are currently pregnant or breast-feeding
- Women of childbearing potential unwilling or unable to use appropriate effective contraception for the first 6 months of the trial
- Known allergy to one or more of the study drugs
- 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
- Taking any immunosuppressive drugs or use of systemic corticosteroids for more than 2 weeks prior to screening
- 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
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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
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03474198
Contact: Christopher Cousins, Project Leader | 65 6601 5371 | mdccdc@nus.edu.sg | |
Contact: Nicholas Paton, Chief Investigator | 65 6601 5371 | nick_paton@nuhs.edu.sg |
Indonesia | |
Universitas Padjadjaran | Recruiting |
Bandung, Indonesia | |
Persahbahatan Hospital | Recruiting |
Jakarta, Indonesia | |
Wahidin Sudirohusodo Hospital | Recruiting |
Makassar, Indonesia | |
Saiful Anwar Hospital | Recruiting |
Malang, Indonesia | |
Soetomo General Hospital | Recruiting |
Surabaya, Indonesia | |
Philippines | |
Perpetual Succour Hospital | Recruiting |
Cebu, Philippines | |
De La Salle Health Sciences Institute | Recruiting |
Manila, Philippines | |
Lung Center Philippines | Recruiting |
Manila, Philippines | |
Philippines Tuberculosis Society Incorporated (PTSI) | Not yet recruiting |
Manila, Philippines | |
Tropical Disease Foundation | Recruiting |
Manila, Philippines | |
Quezon Institute | Recruiting |
Quezon City, Philippines | |
Singapore | |
National University Hospital | Not yet recruiting |
Singapore, Singapore | |
Thailand | |
King Chulalongkorn Memorial Hospital | Recruiting |
Bangkok, Thailand | |
Central Chest Institute of Thailand | Recruiting |
Nonthaburi, Thailand |
Study Director: | Nicholas Paton | National University Hospital, Singapore |
Responsible Party: | University College, London |
ClinicalTrials.gov Identifier: | NCT03474198 |
Other Study ID Numbers: |
TRUNCATE-TB |
First Posted: | March 22, 2018 Key Record Dates |
Last Update Posted: | April 19, 2019 |
Last Verified: | April 2019 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Tuberculosis Tuberculosis, Pulmonary Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses Infections Respiratory Tract Infections Lung Diseases Respiratory Tract Diseases Levofloxacin Rifampin Isoniazid Linezolid |
Pyrazinamide Ethambutol Rifapentine Bedaquiline Clofazimine Anti-Infective Agents, Urinary Anti-Infective Agents Renal Agents Anti-Bacterial Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Cytochrome P-450 CYP1A2 Inhibitors |