Two-month Regimens Using Novel Combinations to Augment Treatment Effectiveness for Drug-sensitive Tuberculosis

Summary

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

Conditions

• Tuberculosis, Pulmonary

Interventions

DRUG

Rifampicin

10mg/kg

DRUG

Isoniazid

5mg/kg

DRUG

Pyrazinamide

25mg/kg

DRUG

Ethambutol

15mg/kg

DRUG

Linezolid

600mg

DRUG

Clofazimine

200mg

DRUG

Rifapentine

1200mg

DRUG

Levofloxacin

1000mg

DRUG

Bedaquiline

400mg once daily for 2 weeks then 200mg 3x a week

DRUG

Rifampicin

35mg/kg

Sponsors & Collaborators

• National University Hospital, Singapore

  collaborator OTHER

• Singapore Clinical Research Institute (SCRI)

  collaborator UNKNOWN

• University College, London

  lead OTHER

Principal Investigators

• Nicholas Paton · National University Hospital, Singapore

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-03-21

Primary Completion

2022-01-20

Completion

2022-01-20

Countries

• India
• Indonesia
• Philippines
• Singapore
• Thailand
• Uganda

Study Locations