Rapid Detection of Rifampin and Isoniazid Resistance by PCR Before Tuberculosis (TB) Treatment Initiation (FAST-TB)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 4

Conditions: Tuberculosis

Treatments: Drug: conventional therapy; Other: PCR-based strategy

Study type: Interventional

Funder types: Other

Identifiers

NCT02231229

P120130 AOM12317

IDRCB2013-A01406-39 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 204 patients

Sex: All

Ages: 18 to 84 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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204 participants in 2 patient groups

PCR-based strategy

Experimental group

Description:

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

Treatment:

Other: PCR-based strategy

conventional therapy

Active Comparator group

Description:

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.

Treatment:

Drug: conventional therapy