TuberculosisPhase 4FAST-TBNCT02231229
Rapid Detection of Rifampin and Isoniazid Resistance by PCR Before Tuberculosis (TB) Treatment Initiation
A Phase 4 study testing PCR-based strategy and conventional therapy in people with Tuberculosis, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial summary
French guidelines currently recommend to initiate a 4-drug containing regimen associating isoniazid (INH or H), rifampicin (RIFor RMP or R), pyrazinamide (PZA or Z) and ethambutol (EMB or E) pending the results of drug susceptibility testing (DST). Read more about this study
- Who is it for?
- Ages 18 to 84 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- PCR-based strategy and conventional therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 204 participants
- Where
- 2 sitesFrance
- Study dates
- 23 Jul 2014to 18 Feb 2020
- Phase
- Phase 4
- 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 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients
- with active pulmonary tuberculosis (TB) and positive respiratory samples on microscopic examination for acid-fast bacilli (AFB+,) who are eligible for a standard TB treatment with a 4 drug combination
- PCR (Genotype MTBDR Plus v2.0, Hain Lifescience) result available within the first 7 days of tuberculosis treatment.
- who are seeking care in France (metropolitan or overseas) and accept a follow-up of 18 to 24 months after inclusion.
- who have had a prior clinical examination
Who cannot join
- Refusal to participate in the study
- Prior history of TB treatment
- For women of child bearing age, pregnancy, willing to become pregnant or breastfeeding
- Patient without healthcare insurance (French social security)
- Patient participating in another clinical trial
- Any condition that might compromise, in the investigator's opinion, patient's compliance with the protocol.
- Results of cultures available at enrollment
- No HIV testing available within the last 3 months prior to inclusion in the study.
Trial locations and contacts
2 sites in 1 country.
France2 sites
Bichat Claude Bernard Hospital
Paris, 75018
Bichat hospital
Paris, 75018
About this study
Official title: Rapid Detection of Rifampin and Isoniazid Resistance by PCR Before Tuberculosis (TB) Treatment Initiation: a National Multicenter Randomized Clinical Trial
French guidelines currently recommend to initiate a 4-drug containing regimen associating isoniazid (INH or H), rifampicin (RIFor RMP or R), pyrazinamide (PZA or Z) and ethambutol (EMB or E) pending the results of drug susceptibility testing (DST). The rationale behind routine use of EMB is to prevent the emergence of resistance to rifampicin (RMP), in case of primary resistance to INH. Hence, early detection of resistance to INH and RIF using molecular testing in Mycobacterium tuberculosis could allow early adaptation of antituberculosis treatment: i) start with a 3-drug containing regimen (i.e. INH, RIF, and PZA); ii) early enforcement of treatment when resistance is suspected, pending in depth susceptibility testings.
the duration of treatment is 6 months or 12 months.
Read the detailed description
The impact of rapid detection of resistance with PCR has been poorly evaluated in low-endemic countries. In France, primary resistance to isoniazid and rifampicin were estimated at, respectively, 5.2%, and 1.2 %. Based on these estimates, French guidelines currently recommends to initiate a 4-drug containing regimen associating isoniazid (INH or H), rifampicin (RIFor RMP or R), pyrazinamide (PZA or Z) and ethambutol (EMB or E) pending the results of drug susceptibility testing (DST). The rationale behind routine use of EMB is to prevent the emergence of resistance to rifampicin (RMP), in case of primary resistance to INH. Hence, early detection of resistance to INH and RIF using molecular testing in Mycobacterium tuberculosis could allow early adaptation of antituberculosis treatment: i) start with a 3-drug containing regimen (i.e. INH, RIF, and PZA), in patients with fully susceptible isolates (currently 95% of cases); ii) early enforcement of treatment when resistance is suspected, pending in depth susceptibility testings. GenoType ®MTB DR plus sensitivity for RIF and INH resistance detection has been estimated at 100% and 83%, respectively.
- Conditions
- Tuberculosis
- Being tested
- PCR-based strategy, conventional therapy
- Keywords
- Pulmonary tuberculosis, Mycobacterium tuberculosis (MTB), Drug Resistance (DR), Isoniazid (INH or H), Rifampicin (RIF or RMP or R), Pyrazinamide (PZA or Z), Ethambutol (EMB or E), Fast-TB, Isoniazid, Rifampicin, Pyrazinamide (HRZ), Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (HRZE), drug susceptibility testing (DST), Acid-Fast Bacilli (AFB+), Polymerase Chain Reaction (PCR)
- Medical subject headings
- Tuberculosis, Tuberculosis, Pulmonary, Sclerotylosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCR-based strategyOther
Also called HRZ combination therapy
Treatment based on the results of detection of resistance to isoniazid and rifampicin using PCR (GenoType ® Mycobacterium Tuberculosis Drug Resistance (MTBDR)plus 2.0) in a smear positive patient with pulmonary tuberculosis: initiation of a 3 drug combination (isoniazid (H / INH); rifampicin (R /RIF); pyrazinamide (Z / PZA)) if no resistance is detected and treatment based on suspected resistance in case of INH and/or RIF resistant strain.
Also called 4 drug combination (HRZE)
Initiation of a standard 4 drug combination (isoniazid (H / INH); rifampicin (R /RIF); pyrazinamide (Z / PZA); ethambutol (EMB or E)) until the results of DST are available.
| Study group | Role | What they receive |
|---|---|---|
| PCR-based strategy | Experimental | PCR-based strategy: after testing for isoniazid and rifampin resistance using a molecular testing with PCR (GenoType ®MTB DR plus), patients will receive HRZ combination therapy (INH , RIF, PZA) if no resistance is detected Receives: Other: PCR-based strategy |
| conventional therapy | Active comparator | Conventional therapy: based on the standard of care in France: initiation of the standard 4 drug regimen INH, RIF, PZA, and EMB, until drug susceptibility testing (DST) results are available. Receives: Drug: conventional therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with treatment success at the end of TB treatment
TB treatment success (cure certain or probable cure) at the end of TB treatment
- cure certain: negative sputum cultures or negative sputum direct examination in a patient who has completed treatment and have never filled the definition of treatment failure.
- probable cure: clinical and radiological improvement of symptoms associated with tuberculosis in a patient who has completed treatment and have never filled the definition of treatment failure.
- completed treatment: patients who took more than 80% of prescribed treatment.
- clinical improvement: improvement in overall score of Teeter AND no weight loss
- radiological improvement: between baseline and end of treatment
- failure: if Positive sputum culture after 5 months of treatment, death during treatment whatever the cause, treatment interrupted for more than two months, decision of the clinician to change TB treatment because of the suspicion of failure after 5 months of TB treatment
Measured: 6 or 12 months after enrollment
Secondary outcomes (5)
Proportion of patients with relapse
positive culture of respiratory sample after TB treatment and after having had negative cultures during treatment or decision by the clinician to restart treatment because of suspicion of relapse
Measured: within 12 months after the end of TB treatment
Proportion of patients with failure
proportion of patients with treatment changes or discontinuations including the proportion of subjects stopping strategy and treatment assigned at randomization, and the delay between the stop and inclusion.
Will not be considered modifications or discontinuations:
- adaptation of treatment on the results of susceptibility testing in the conventional arm (adaptations following the susceptibility in the PCR arm will therefore be considered as a modification).
- switching to bitherapy in the 2 arms.
Measured: 6 or 12 months after enrollment
Capillary drug concentration, for each of the prescribed treatment in hair segments
measure of drug concentrations in hair segments, for each of the prescribed treatment, in order to estimate treatment observance and if drug hair concentrations are associated with therapy success or toxicity
Measured: at 2 and 6 months
Incidence and nature of grade 3 or grade 4 adverse events related or not to TB treatments
comparison between the 2 arms of incidence and nature of grade 3 or grade 4 adverse events related or not to TB treatments
Measured: 6 months or at the latest 12 months after enrollment
Direct medical costs associated with each strategy
comparison of direct medical costs induced by PCR strategy and by conventional strategy
Measured: within 18 or at the latest 12 months after enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2014 (estimated)
- Study start23 Jul 2014
- Primary completion4 Jul 2018
- Study completion18 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 204 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yazdan Yazdanpanah, MD-PHD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02231229
- Sponsor's protocol ID
- P120130 AOM12317
- Other IDs
- IDRCB2013-A01406-39
- Acronym
- FAST-TB
- Status last verified
- Mar 2020
- First submitted
- 3 Jul 2014
- Last updated
- 18 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rapid Detection of Rifampin and Isoniazid Resistance by PCR Before Tuberculosis (TB) Treatment Initiation: a National Multicenter Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02231229
- Acronym / sponsor ID
- FAST-TB / P120130 AOM12317
- Conditions
- Tuberculosis
- Keywords
- Pulmonary tuberculosis, Mycobacterium tuberculosis (MTB), Drug Resistance (DR), Isoniazid (INH or H), Rifampicin (RIF or RMP or R), Pyrazinamide (PZA or Z), Ethambutol (EMB or E), Fast-TB
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 204 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 23 Jul 2014 (actual)
- Primary completion
- 4 Jul 2018 (actual)
- Study completion
- 18 Feb 2020 (actual)
- First posted
- 4 Sep 2014 (estimated)
- 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.
French guidelines currently recommend to initiate a 4-drug containing regimen associating isoniazid (INH or H), rifampicin (RIFor RMP or R), pyrazinamide (PZA or Z) and ethambutol (EMB or E) pending the results of drug susceptibility testing (DST). The rationale behind routine use of EMB is to prevent the emergence of resistance to rifampicin (RMP), in case of primary resistance to INH. Hence, early detection of resistance to INH and RIF using molecular testing in Mycobacterium tuberculosis could allow early adaptation of antituberculosis treatment: i) start with a 3-drug containing regimen (i.e. INH, RIF, and PZA); ii) early enforcement of treatment when resistance is suspected, pending in depth susceptibility testings.
the duration of treatment is 6 months or 12 months.
Detailed description
The impact of rapid detection of resistance with PCR has been poorly evaluated in low-endemic countries. In France, primary resistance to isoniazid and rifampicin were estimated at, respectively, 5.2%, and 1.2 %. Based on these estimates, French guidelines currently recommends to initiate a 4-drug containing regimen associating isoniazid (INH or H), rifampicin (RIFor RMP or R), pyrazinamide (PZA or Z) and ethambutol (EMB or E) pending the results of drug susceptibility testing (DST). The rationale behind routine use of EMB is to prevent the emergence of resistance to rifampicin (RMP), in case of primary resistance to INH. Hence, early detection of resistance to INH and RIF using molecular testing in Mycobacterium tuberculosis could allow early adaptation of antituberculosis treatment: i) start with a 3-drug containing regimen (i.e. INH, RIF, and PZA), in patients with fully susceptible isolates (currently 95% of cases); ii) early enforcement of treatment when resistance is suspected, pending in depth susceptibility testings. GenoType ®MTB DR plus sensitivity for RIF and INH resistance detection has been estimated at 100% and 83%, respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PCR-based strategy | Experimental | Other: PCR-based strategyPCR-based strategy: after testing for isoniazid and rifampin resistance using a molecular testing with PCR (GenoType ®MTB DR plus), patients will receive HRZ combination therapy (INH , RIF, PZA) if no resistance is detected |
| conventional therapy | Active comparator | Drug: conventional therapyConventional therapy: based on the standard of care in France: initiation of the standard 4 drug regimen INH, RIF, PZA, and EMB, until drug susceptibility testing (DST) results are available. |
Who may qualify
- Ages
- 18 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients
- with active pulmonary tuberculosis (TB) and positive respiratory samples on microscopic examination for acid-fast bacilli (AFB+,) who are eligible for a standard TB treatment with a 4 drug combination
- PCR (Genotype MTBDR Plus v2.0, Hain Lifescience) result available within the first 7 days of tuberculosis treatment.
- who are seeking care in France (metropolitan or overseas) and accept a follow-up of 18 to 24 months after inclusion.
- who have had a prior clinical examination
Key exclusion criteria (8 listed)
- Refusal to participate in the study
- Prior history of TB treatment
- For women of child bearing age, pregnancy, willing to become pregnant or breastfeeding
- Patient without healthcare insurance (French social security)
- Patient participating in another clinical trial
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 |
|---|---|---|
| PCR-based strategyAlso: HRZ combination therapyTreatment based on the results of detection of resistance to isoniazid and rifampicin using PCR (GenoType ® Mycobacterium Tuberculosis Drug Resistance (MTBDR)plus 2.0) in a smear positive patient with pulmonary tuberculosis: initiation of a 3 drug combination (isoniazid (H / INH); rifampicin (R /RIF); pyrazinamide (Z / PZA)) if no resistance is detected and treatment based on suspected resistance in case of INH and/or RIF resistant strain. | Other | PCR-based strategy |
| conventional therapyAlso: 4 drug combination (HRZE)Initiation of a standard 4 drug combination (isoniazid (H / INH); rifampicin (R /RIF); pyrazinamide (Z / PZA); ethambutol (EMB or E)) until the results of DST are available. | Drug | conventional therapy |
Primary outcome
Proportion of patients with treatment success at the end of TB treatment
Time frame: 6 or 12 months after enrollment
TB treatment success (cure certain or probable cure) at the end of TB treatment * cure certain: negative sputum cultures or negative sputum direct examination in a patient who has completed treatment and have never filled the definition of treatment failure. * probable cure: clinical and radiological improvement of symptoms associated with tuberculosis in a patient who has completed treatment and have never filled the definition of treatment failure. * completed treatment: patients who took more than 80% of prescribed treatment. * clinical improvement: improvement in overall score of Teeter AND no weight loss * radiological improvement: between baseline and end of treatment * failure: if Positive sputum culture after 5 months of treatment, death during treatment whatever the cause, treatment interrupted for more than two months, decision of the clinician to change TB treatment because of the suspicion of failure after 5 months of TB treatment
5 secondary outcomes
Proportion of patients with relapse
Time frame: within 12 months after the end of TB treatment
Proportion of patients with failure
Time frame: 6 or 12 months after enrollment
Capillary drug concentration, for each of the prescribed treatment in hair segments
Time frame: at 2 and 6 months
Incidence and nature of grade 3 or grade 4 adverse events related or not to TB treatments
Time frame: 6 months or at the latest 12 months after enrollment
Direct medical costs associated with each strategy
Time frame: within 18 or at the latest 12 months after enrolment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2020.
- Individual participant dataSharing planned: Undecided
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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.
Yazdan Yazdanpanah, MD-PHD principal investigator
Assistance Publique - Hôpitaux de Paris
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing PCR-based strategy and conventional therapy in people with Tuberculosis, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
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 5 inclusion and 8 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: finished, as of the sponsor's last update on 18 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 treatment success at the end of TB treatment (time frame: 6 or 12 months after enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Mar 2020.