Tuberculosis, PulmonaryNCT04783727
PredictEndTB Signature for Individualizing Treatment in Multidrug-Resistant Tuberculosis
A study testing Individualised treatment duration based on RNA transcriptomic model in people with Tuberculosis, Pulmonary and Tuberculosis, Multidrug-Resistant, run by Research Center Borstel at 5 sites in 4 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Bacterial Infections
- What is being tested?
- Individualised treatment duration based on RNA transcriptomic model
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 1 Apr 2021to 1 Nov 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Ukraine2 sites
Kharkiv National Medical University
Kharkiv, 61000
National Pirogov Memorial Medical University
Vinnytsia, 21018
About this study
Official title: Personalized Therapy Durations Defined by the Blood RNA-based Model 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.
Read the 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.
- Conditions
- Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Bacterial Infections, Mycobacterial Infection
- Being tested
- Individualised treatment duration based on RNA transcriptomic model
- Keywords
- tuberculosis, multidrug resistance, treatment duration
- Medical subject headings
- Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Bacterial Infections, Mycobacterium Infections, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Individualised treatment duration based on RNA transcriptomic modelDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | The individualised treatment durations defined by the RNA transcriptomic signature-based model Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 36 months
Secondary outcomes (4)
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
Measured: up to 24 months
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
Measured: up to 24 months
Proportion of patients who died from TB
This outcome measure will be used in the secondary efficacy analysis in the Intention-to-Treat population
Measured: up to 36 months
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
Measured: up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2021
- Study start1 Apr 2021
- Primary completion1 Nov 2022
- Study completion1 Nov 2022
Why it stopped: Change in WHO recommendations for standard of care (control arm); availability of new shorter treatment regimens for MDR-TB; war in Ukraine where two study sites are located; key trial team members left the team.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis, PulmonaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Research Center Borstel
- Sponsor type
- University, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich
- Responsible party
- Sponsor
- Investigators
- Jan Heyckendorf, MD, Principal investigator, Research Center Borstel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04783727
- Sponsor's protocol ID
- PredictEndTBSignature
- Status last verified
- Dec 2023
- First submitted
- 2 Mar 2021
- Last updated
- 13 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: All study data will be pseudonymised and shared with other researchers only in pseudonymised form
Publications
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.
PubMed 33574078Heyckendorf 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.
PubMed 34331877
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalized Therapy Durations Defined by the Blood RNA-based Model for Individualizing Treatment in Multidrug-Resistant Tuberculosis
- ClinicalTrials.gov ID
- NCT04783727
- Acronym / sponsor ID
- PredictEndTBSignature
- Conditions
- Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Bacterial Infections, Mycobacterial Infection
- Keywords
- tuberculosis, multidrug resistance, treatment duration
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Change in WHO recommendations for standard of care (control arm); availability of new shorter treatment regimens for MDR-TB; war in Ukraine where two study sites are located; key trial team members left the team.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Research Center BorstelUniversity, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 1 Nov 2022 (actual)
- Study completion
- 1 Nov 2022 (actual)
- First posted
- 5 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Diagnostic Test: Individualised treatment duration based on RNA transcriptomic modelThe individualised treatment durations defined by the RNA transcriptomic signature-based model |
| Control arm | No intervention | –The locally accepted standard duration of treatment based on the WHO recommendation for treatment of MDR-TB patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Individualised treatment duration based on RNA transcriptomic modelAnti-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. | Diagnostic test | Experimental arm |
Primary outcome
Proportion of patients with favourable study outcome 12 months after treatment end
Time frame: 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.
4 secondary outcomes
Proportion of patients who was lost to follow-up during treatment
Time frame: up to 24 months
Proportion of patients who had a treatment failure
Time frame: up to 24 months
Proportion of patients who died from TB
Time frame: up to 36 months
Proportion of patients who died of any cause
Time frame: up to 36 months
Results and safety
The study was stopped early (reason given: Change in WHO recommendations for standard of care (control arm); availability of new shorter treatment regimens for MDR-TB; war in Ukraine where two study sites are located; key trial team members left the team.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2023.
- Background: PubMed 33574078Heyckendorf 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.
- Background: PubMed 34331877Heyckendorf 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.
- Individual participant dataSharing planned: No. All study data will be pseudonymised and shared with other researchers only in pseudonymised form
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Heyckendorf, MD principal investigator
Research Center Borstel
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Individualised treatment duration based on RNA transcriptomic model in people with Tuberculosis, Pulmonary and Tuberculosis, Multidrug-Resistant, run by Research Center Borstel at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Ukraine, Germany, Moldova, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Change in WHO recommendations for standard of care (control arm); availability of new shorter treatment regimens for MDR-TB; war in Ukraine where two study sites are located; key trial team members left the team.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with favourable study outcome 12 months after treatment end (time frame: up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04783727, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2023.