Clinical trial NCT04783727: PredictEndTB Signature for Individualizing Treatment in Multidrug-Resistant Tuberculosis
Official title: Personalized Therapy Durations Defined by the Blood RNA-based Model for Individualizing Treatment in Multidrug-Resistant Tuberculosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Tuberculosis, Pulmonary
Tuberculosis, Multidrug-Resistant
Bacterial Infections
Mycobacterial Infection
Keywords: tuberculosis
multidrug resistance
treatment duration
Lead sponsor: Research Center Borstel
Sponsor class: OTHER
Collaborators: name: Ludwig-Maximilians - University of Munich
First posted: 2021-03-05
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients with favourable study outcome 12 months after treatment end
timeFrame: up to 36 months
Secondary outcomes:
measure: Proportion of patients who was lost to follow-up during treatment
timeFrame: up to 24 months
measure: Proportion of patients who had a treatment failure
timeFrame: up to 24 months
measure: Proportion of patients who died from TB
timeFrame: up to 36 months
measure: Proportion of patients who died of any cause
timeFrame: up to 36 months
Other outcomes:
measure: Proportion of patients experiencing adverse events
timeFrame: up to 24 months
measure: Proportion of patients who experienced TB relapse that was identified on early stages
timeFrame: up to 36 months
measure: Characteristics of the transcriptomic signatures obtained at the end of therapy time point and at follow-up visits
timeFrame: up to 36 months
Locations:
city: Borstel
country: Germany
facility: Research Center Borstel
state: Schleswig-Holstein
city: Chisinau
country: Moldova, Republic of
facility: Phthisiopneumology Institute Chiril Draganiuc
city: Bucharest
country: Romania
facility: Marius Nasta Pulmonology Institute
city: Kharkiv
country: Ukraine
facility: Kharkiv National Medical University
city: Vinnytsia
country: Ukraine
facility: National Pirogov Memorial Medical University
Study officials:
affiliation: Research Center Borstel
name: Jan Heyckendorf, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.