PredictEndTB Signature for Individualizing Treatment in Multidrug-Resistant Tuberculosis

NCT04783727 | Terminated DMC

• 1 other identifier: PredictEndTBSignature
• Study Type: interventional
• Target: 4
• Locations: 4 countries
• Sites: 5

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.

Conditions

Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant; Bacterial Infections; Mycobacterial Infection

Keywords

tuberculosis; multidrug resistance; treatment duration

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with favourable study outcome 12 months after treatment end

  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.

  up to 36 months

Secondary Outcomes (4)

• Proportion of patients who was lost to follow-up during treatment

  up to 24 months

• Proportion of patients who had a treatment failure

  up to 24 months

• Proportion of patients who died from TB

  up to 36 months

• Proportion of patients who died of any cause

  up to 36 months

Other Outcomes (3)

• Proportion of patients experiencing adverse events

  up to 24 months

• Proportion of patients who experienced TB relapse that was identified on early stages

  up to 36 months

• Characteristics of the transcriptomic signatures obtained at the end of therapy time point and at follow-up visits

  up to 36 months

Study Arms (2)

Experimental arm

EXPERIMENTAL

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

Diagnostic Test: Individualised treatment duration based on RNA transcriptomic model

Control arm

NO INTERVENTION

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

Interventions

Individualised treatment duration based on RNA transcriptomic model DIAGNOSTIC_TEST

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.

Experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Research Center Borstel: lead
• Ludwig-Maximilians - University of Munich: collaborator

Study Sites (5)

Research Center Borstel

Borstel, Schleswig-Holstein, 23845, Germany

Location

Phthisiopneumology Institute Chiril Draganiuc

Chisinau, 2025, Moldova

Location

Marius Nasta Pulmonology Institute

Bucharest, Romania

Location

Kharkiv National Medical University

Kharkiv, 61000, Ukraine

Location

National Pirogov Memorial Medical University

Vinnytsia, 21018, Ukraine

Location

Related Publications (2)

• Heyckendorf J, Marwitz S, Reimann M, Avsar K, DiNardo AR, Gunther G, Hoelscher M, Ibraim E, Kalsdorf B, Kaufmann SHE, Kontsevaya I, van Leth F, Mandalakas AM, Maurer FP, Muller M, Nitschkowski D, Olaru ID, Popa C, Rachow A, Rolling T, Rybniker J, Salzer HJF, Sanchez-Carballo P, Schuhmann M, Schaub D, Spinu V, Suarez I, Terhalle E, Unnewehr M, Weiner J 3rd, Goldmann T, Lange C. Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model. Eur Respir J. 2021 Sep 2;58(3):2003492. doi: 10.1183/13993003.03492-2020. Print 2021 Sep.

  PMID: 33574078 BACKGROUND

• Heyckendorf J, Reimann M, Marwitz S, Lange C; DZIF-TB cohort study group. Pathogen-free diagnosis of tuberculosis. Lancet Infect Dis. 2021 Aug;21(8):1066. doi: 10.1016/S1473-3099(21)00337-6. No abstract available.

  PMID: 34331877 BACKGROUND

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant; Bacterial Infections; Mycobacterium Infections; Tuberculosis

Condition Hierarchy (Ancestors)

Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jan Heyckendorf, MD

  Research Center Borstel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 5, 2021
• Study Start: April 1, 2021
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2022
• Last Updated: December 13, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

UA (2); RO (1); DE (1); MO (1)