New treatment for pulmonary TB with High dose Rifampicin, High dose Moxifloxacin and Linezolid

A Multicentre Controlled Open Randomized Clinical Trial to evaluate the efficacy and safety profile of an anti-TB drug combination based on High Dose Rifampicin, High Dose Moxifloxacin and Linezolid daily for DS AFB smear positive pulmonary TB patients during the initial 8 weeks of treatment. - RML-TB study

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-001626-22-ES

Enrollment

120

Registered

2022-03-29

Start date

2022-03-28

Completion date

Unknown

Last updated

2022-04-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Smear-positive rifampicin-sensitive pulmonary Tuberculosis

Interventions

Trade Name: Rifampicin Pharmaceutical Form: Capsule, hard

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1) Diagnosis of AFB smear-positive pulmonary TB. 2) Age = 18 years. 3) Sign informed consent. 4) Negative pregnancy test (women of childbearing age) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20

Exclusion criteria

Exclusion criteria: 1) Contact of a patient with multidrug-resistant TB. 2) Multidrug-resistant TB or monoresistance to any first-line drugs (except ethambutol). 3) AFB smear-positive pulmonary TB with negative mycobacterial culture. 4) Barthel 3x Upper limit of normality b) Bit> x3 Upper limit of normality c) Hb 0.5s b) Other clinically relevant changes in the ECG according to investigator criteria. 22) Treatment with any of the study drugs in the last month for more than 7 days.

Design outcomes

Primary

Measure	Time frame
Primary end point(s): The efficacy outcome is defined as the proportion of patients with sputum sterilization in liquid media culture at 8 weeks after treatment onset. Sputum culture negativization / sterilization: a participant with positive culture at the beginning of the treatment, but who has a negative culture at 8 weeks after treatment onset. Participants without signs or symptoms of active TB at 8 weeks after treatment onset and unable to produce a sputum specimen. Efficacy subset (per protocol): group of participants that have completed 75% of the treatment dosages and have provided 8-week sputum sample. Efficacy subset (Intention to treat): group of patients randomized to the experimental or standard arm regardless treatment adherence. Participants with no sample collected at 8-week will be considered as having sputum positive culture at 8 weeks (includes death due to TB, lost to follow up, referrals). Participant with treatment shift will also be considered as having sputum positive culture at 8 weeks. Decrease in linezolid dose is permitted during the first two weeks and will not be considered treatment shift. Non-assessable: participants who die due to a cause not related to TB or the study treatment. Participant will be considered with sputum culture negativization at 8 weeks if the last known sputum culture was negative. The safety outcome is defined as the proportion of patient with grade 3 or superior adverse event. Safety / Toxicity: a patient experiencing a severe adverse event (grade 3 or superior according to the CTEAE version 5). Tolerability: a patient experiencing any adverse event according to the CTCAE version 5. Safety subset (per protocol): includes all participants who completed assigned follow up and are at least 75% adherent to the treatment. Safety subset (intention to treat): includes all participants that received at least one dose of the study drugs. Modified safety subset (per procotol): includes all participants who completed assi	—

Measure

Time frame

Primary end point(s): The efficacy outcome is defined as the proportion of patients with sputum sterilization in liquid media culture at 8 weeks after treatment onset. Sputum culture negativization / sterilization: a participant with positive culture at the beginning of the treatment, but who has a negative culture at 8 weeks after treatment onset. Participants without signs or symptoms of active TB at 8 weeks after treatment onset and unable to produce a sputum specimen. Efficacy subset (per protocol): group of participants that have completed 75% of the treatment dosages and have provided 8-week sputum sample. Efficacy subset (Intention to treat): group of patients randomized to the experimental or standard arm regardless treatment adherence. Participants with no sample collected at 8-week will be considered as having sputum positive culture at 8 weeks (includes death due to TB, lost to follow up, referrals). Participant with treatment shift will also be considered as having sputum positive culture at 8 weeks. Decrease in linezolid dose is permitted during the first two weeks and will not be considered treatment shift. Non-assessable: participants who die due to a cause not related to TB or the study treatment. Participant will be considered with sputum culture negativization at 8 weeks if the last known sputum culture was negative. The safety outcome is defined as the proportion of patient with grade 3 or superior adverse event. Safety / Toxicity: a patient experiencing a severe adverse event (grade 3 or superior according to the CTEAE version 5). Tolerability: a patient experiencing any adverse event according to the CTCAE version 5. Safety subset (per protocol): includes all participants who completed assigned follow up and are at least 75% adherent to the treatment. Safety subset (intention to treat): includes all participants that received at least one dose of the study drugs. Modified safety subset (per procotol): includes all participants who completed assi

—

Secondary

Measure	Time frame
Secondary end point(s): a) To evaluate the tolerability (any adverse event) of high-dose rifampicin, high dose moxifloxacin and linezolid for 8 weeks. B)To evaluate the efficacy dynamics of the study intervention as time-dependent decline in sputum smear bacterial load and time-dependent increase in time-to-positivity of sputum culture between arms. C) To analyze the correlation between the AUC/MIC values for rifampicin, moxifloxacin and linezolid and the efficacy outcomes. D) To evaluate the quality of life using SF-12 and St Geroge’s respiratory questionnaire among participants and compare study arms. E) To conduct a cost-effectiveness study to explore the feasibility of implementing the experimental arm in the Spanish National Health System.;Timepoint(s) of evaluation of this end point: 8 weeks	—

Measure

Time frame

Secondary end point(s): a) To evaluate the tolerability (any adverse event) of high-dose rifampicin, high dose moxifloxacin and linezolid for 8 weeks. B)To evaluate the efficacy dynamics of the study intervention as time-dependent decline in sputum smear bacterial load and time-dependent increase in time-to-positivity of sputum culture between arms. C) To analyze the correlation between the AUC/MIC values for rifampicin, moxifloxacin and linezolid and the efficacy outcomes. D) To evaluate the quality of life using SF-12 and St Geroge’s respiratory questionnaire among participants and compare study arms. E) To conduct a cost-effectiveness study to explore the feasibility of implementing the experimental arm in the Spanish National Health System.;Timepoint(s) of evaluation of this end point: 8 weeks

—

Countries

Spain

Contacts

Public ContactAdrian Sanchez-Montalva

Vall d'Hebron Institute of Research

adrian.sanchez.montalva@gmail.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026