Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| IDRCB2013-A01406-39 | Other Identifier | FRENCH AUTHORITY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PCR-based strategy | Experimental | 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 |
|
| conventional therapy | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PCR-based strategy | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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
| 6 or 12 months after enrollment |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | within 12 months after the end of TB treatment |
| Proportion of patients with failure |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Yazdan Yazdanpanah, MD-PHD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bichat Claude Bernard Hospital | Paris | 75018 | France | |||
| Bichat hospital |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D014397 | Tuberculosis, Pulmonary |
| C537526 | Sclerotylosis |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| conventional therapy | 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. |
|
|
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:
|
| 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 | 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 | 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 | within 18 or at the latest 12 months after enrolment |
| Paris |
| 75018 |
| France |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |