PredictEndTB Signature for Individualizing Treatment in Multidrug-Resistant Tuberculosis
PredictEndTB Signature for Individualizing Treatment in Multidrug-Resistant Tuberculosis
PredictEndTB signature is a non-inferiority, prospective, parallel-group open-label
 randomized controlled trial evaluating the efficacy of individualised antituberculous
 treatment durations that utilize the transcriptomic signature-based model compared to the
 standardised twenty months treatment in a cohort of multidrug-resistant tuberculosis
 patients.
This study is a non-inferiority, prospective, parallel-group open-label randomized controlled
 trial. Three hundred forty-two HIV-negative patients diagnosed with pulmonary tuberculosis
 (TB) and starting a new anti-multidrug-resistant tuberculosis (MDR-TB) treatment cycle will
 be included in the study. Two randomized arms of 171 patients each will be recruited over the
 two-year period, each patient will be followed-up over the entire course of anti-TB treatment
 and one year after the end of therapy. Regular study visits will include physical
 examination, collection of sputum, blood and urine and filling in the study questionnaire. On
 the collected specimens standard bacteriological and blood tests, as well as extended
 immunological analysis, will be performed. In the experimental group, an RNA transcriptomic
 analysis using RNA-Seq technology will also be performed.

 In the control arm, the patients will receive a standardised World Health Organization
 recommended 20 months treatment while in the experimental arm the treatment duration will be
 guided by the transcriptomic signature-based model.

 Treatment outcomes and level of TB relapse and survival within the follow-up period will be
 compared between the experimental and control arms. The efficacy of biomarker-guided
 treatment therapy will be assessed by a comparison of the proportions of favourable study
 outcome between two arms.
Inclusion Criteria:

 -  Patient starting an MDR-TB treatment or within the first 4 weeks after treatment
 initiation and before culture conversion.

 -  Rifampicin resistant M. tuberculosis detected in sputum using a nucleic acid
 amplification test.

 -  New case of TB or re-treatment.

 -  Can give informed consent at the point of recruitment.

 -  Contactable (residing in the area covered by participating TB centres and possessing a
 landline or a mobile phone).

 -  Willing to participate for the entire course of the treatment and extensive follow-up.

 Exclusion Criteria:

 -  Age <18 years old.

 -  Anti-MDR-TB therapy within 6 months prior to the start date of the current treatment
 cycle.

 -  HIV infection.

 -  Non-adherent patient with frequent interruptions.

 -  Patient in custodianship or guardianship.

 -  Late exclusion criterion: no positive cultures at inclusion and within the first 3
 months of treatment.