PredictEndTB Signature for Individualizing Treatment in Multidrug-Resistant Tuberculosis

Bacterial Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04783727
• Other study ID #: PredictEndTBSignature
• Status: Terminated
• Phase: N/A
• Start date: April 1, 2021
• Est. completion date: November 1, 2022

Study information

• Verified date: December 2023
• Source: Research Center Borstel
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: November 1, 2022
• Est. primary completion date: November 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Infections
• Mycobacterial Infection
• Mycobacterium Infections
• Tuberculosis
• Tuberculosis, Multidrug-Resistant
• Tuberculosis, Pulmonary

Intervention

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.

Locations

Country	Name	City	State
Germany	Research Center Borstel	Borstel	Schleswig-Holstein
Moldova, Republic of	Phthisiopneumology Institute Chiril Draganiuc	Chisinau
Romania	Marius Nasta Pulmonology Institute	Bucharest
Ukraine	Kharkiv National Medical University	Kharkiv
Ukraine	National Pirogov Memorial Medical University	Vinnytsia

Sponsors (2)

Lead Sponsor	Collaborator
Research Center Borstel	Ludwig-Maximilians - University of Munich

Countries where clinical trial is conducted

Germany,  Moldova, Republic of,  Romania,  Ukraine, 

References & 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of patients experiencing adverse events	This outcome measure will be used in the exploratory safety analysis in the safety population	up to 24 months
Other	Proportion of patients who experienced TB relapse that was identified on early stages	This outcome measure will be used in the safety analysis in the safety population	up to 36 months
Other	Characteristics of the transcriptomic signatures obtained at the end of therapy time point and at follow-up visits	This outcome measure will be used in the exploratory safety analysis in the safety population	up to 36 months
Primary	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	Proportion of patients who was lost to follow-up during treatment	This outcome measure will be used in the secondary efficacy analysis in the Intention-to-Treat population	up to 24 months
Secondary	Proportion of patients who had a treatment failure	This outcome measure will be used in the secondary efficacy analysis in the Intention-to-Treat population	up to 24 months
Secondary	Proportion of patients who died from TB	This outcome measure will be used in the secondary efficacy analysis in the Intention-to-Treat population	up to 36 months
Secondary	Proportion of patients who died of any cause	This outcome measure will be used in the secondary efficacy analysis in the Intention-to-Treat population	up to 36 months