Clinical trial NCT02231229: Rapid Detection of Rifampin and Isoniazid Resistance by PCR Before Tuberculosis (TB) Treatment Initiation
Official title: Rapid Detection of Rifampin and Isoniazid Resistance by PCR Before Tuberculosis (TB) Treatment Initiation: a National Multicenter Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
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
Isoniazid, Rifampicin, Pyrazinamide (HRZ)
Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (HRZE)
drug susceptibility testing (DST)
Acid-Fast Bacilli (AFB+)
Polymerase Chain Reaction (PCR)
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2014-09-04
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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). 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Proportion of patients with treatment success at the end of TB treatment
timeFrame: 6 or 12 months after enrollment
Secondary outcomes:
measure: Proportion of patients with relapse
timeFrame: within 12 months after the end of TB treatment
measure: Proportion of patients with failure
timeFrame: 6 or 12 months after enrollment
measure: Capillary drug concentration, for each of the prescribed treatment in hair segments
timeFrame: at 2 and 6 months
measure: Incidence and nature of grade 3 or grade 4 adverse events related or not to TB treatments
timeFrame: 6 months or at the latest 12 months after enrollment
measure: Direct medical costs associated with each strategy
timeFrame: within 18 or at the latest 12 months after enrolment
Other outcomes:
Locations:
city: Paris
country: France
facility: Bichat Claude Bernard Hospital
city: Paris
country: France
facility: Bichat hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Yazdan Yazdanpanah, MD-PHD
role: PRINCIPAL_INVESTIGATOR
References: