Rapid Detection of Rifampin and Isoniazid Resistance by PCR Before Tuberculosis (TB) Treatment Initiation
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): PCR-based strategy; conventional therapy
Intervention type(s): Other; Drug
Intervention description(s): 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.
Other intervention name(s): HRZ combination therapy; 4 drug combination (HRZE)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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)