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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
204
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.
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.
Bichat Claude Bernard Hospital
Paris, France
Bichat hospital
Paris, France
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
Time frame: 6 or 12 months after enrollment
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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: within 18 or at the latest 12 months after enrolment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.