PredictEndTB Signature for Individualizing Treatment in Multidrug-Resistant Tuberculosis

Sponsor

Research Center Borstel (Other)

Overall Status

Recruiting

CT.gov ID

NCT04783727

Collaborator

Ludwig-Maximilians - University of Munich (Other)

342

Enrollment

Locations

Arms

Anticipated Duration (Months)

68.4

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis, Pulmonary Tuberculosis, Multidrug-Resistant Bacterial Infections Mycobacterial Infection	Diagnostic Test: Individualised treatment duration based on RNA transcriptomic model	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

342 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Masking Description:

During the treatment, both Participant and Care Provider will be masked but once the treatment end is achieved, they will be unmasked, and study participation is continued.

Primary Purpose:

Treatment

Official Title:

Personalized Therapy Durations Defined by the Blood RNA-based Model for Individualizing Treatment in Multidrug-Resistant Tuberculosis

Actual Study Start Date :

Apr 1, 2021

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental arm The individualised treatment durations defined by the RNA transcriptomic signature-based model	Diagnostic Test: Individualised treatment duration based on RNA transcriptomic model Anti-MDR-TB treatment with standard drugs and individual treatment duration guided by the RNA transcriptomic model; may be shorter or longer than standard WHO-recommended treatment duration of 20 months.
No Intervention: Control arm The locally accepted standard duration of treatment based on the WHO recommendation for treatment of MDR-TB patients

Arm

Intervention/Treatment

Experimental: Experimental arm

The individualised treatment durations defined by the RNA transcriptomic signature-based model

Diagnostic Test: Individualised treatment duration based on RNA transcriptomic model

Anti-MDR-TB treatment with standard drugs and individual treatment duration guided by the RNA transcriptomic model; may be shorter or longer than standard WHO-recommended treatment duration of 20 months.

No Intervention: Control arm

The locally accepted standard duration of treatment based on the WHO recommendation for treatment of MDR-TB patients

Outcome Measures

Primary Outcome Measures

Proportion of patients with favourable study outcome 12 months after treatment end [up to 36 months]
The non-inferiority of the experimental arm compared to the control arm will be established if in the Per-Protocol population the difference in proportions of patients with a favourable study outcome between study arms is greater than the lower equivalence margin of 12%. This outcome measure is assessed after up to 24 months of treatment (usually 20 months) plus 12 months of follow-up after the end of treatment.

Secondary Outcome Measures

Proportion of patients who was lost to follow-up during treatment [up to 24 months]
This outcome measure will be used in the secondary efficacy analysis in the Intention-to-Treat population
Proportion of patients who had a treatment failure [up to 24 months]
This outcome measure will be used in the secondary efficacy analysis in the Intention-to-Treat population
Proportion of patients who died from TB [up to 36 months]
This outcome measure will be used in the secondary efficacy analysis in the Intention-to-Treat population
Proportion of patients who died of any cause [up to 36 months]
This outcome measure will be used in the secondary efficacy analysis in the Intention-to-Treat population

Other Outcome Measures

Proportion of patients experiencing adverse events [up to 24 months]
This outcome measure will be used in the exploratory safety analysis in the safety population
Proportion of patients who experienced TB relapse that was identified on early stages [up to 36 months]
This outcome measure will be used in the safety analysis in the safety population
Characteristics of the transcriptomic signatures obtained at the end of therapy time point and at follow-up visits [up to 36 months]
This outcome measure will be used in the exploratory safety analysis in the safety population

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Center Borstel	Borstel	Schleswig-Holstein	Germany	23845
2	Phthisiopneumology Institute Chiril Draganiuc	Chisinau		Moldova, Republic of	2025
3	Marius Nasta Pulmonology Institute	Bucharest		Romania
4	Kharkiv National Medical University	Kharkiv		Ukraine	61000
5	National Pirogov Memorial Medical University	Vinnytsia		Ukraine	21018