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

NCT ID: NCT02231229

Last Updated: 2020-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-23
• Study Completion Date: 2020-02-18

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.

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PCR-based strategy

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

Group Type: EXPERIMENTAL

PCR-based strategy

Intervention Type: OTHER

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.

conventional therapy

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.

Group Type: ACTIVE_COMPARATOR

conventional therapy

Intervention Type: DRUG

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.

Interventions

PCR-based strategy

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.

Intervention Type: OTHER

conventional therapy

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.

Intervention Type: DRUG

Other Intervention Names

HRZ combination therapy; 4 drug combination (HRZE)

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 84 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yazdan Yazdanpanah, MD-PHD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Bichat Claude Bernard Hospital

Paris, , France

Bichat hospital

Paris, , France

Countries

France

Other Identifiers

IDRCB2013-A01406-39

Identifier Type: OTHER

Identifier Source: secondary_id

P120130 AOM12317

Identifier Type: -

Identifier Source: org_study_id