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

NCT02231229 | Completed Phase 4

• 2 other identifiers: P120130 AOM12317IDRCB2013-A01406-39
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 2

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.

Conditions

Tuberculosis

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)

Outcome Measures

Primary Outcomes (1)

• 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

  6 or 12 months after enrollment

Secondary Outcomes (5)

• Proportion of patients with relapse

  within 12 months after the end of TB treatment

• Proportion of patients with failure

  6 or 12 months after enrollment

• Capillary drug concentration, for each of the prescribed treatment in hair segments

  at 2 and 6 months

• 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

  within 18 or at the latest 12 months after enrolment

Study Arms (2)

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

Other: PCR-based strategy

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.

Drug: conventional therapy

Interventions

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.

Also known as: HRZ combination therapy

PCR-based strategy

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.

Also known as: 4 drug combination (HRZE)

conventional therapy

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 have had a prior clinical examination

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Bichat Claude Bernard Hospital

Paris, 75018, France

Location

Bichat hospital

Paris, 75018, France

Location

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Pulmonary; Sclerotylosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yazdan Yazdanpanah, MD-PHD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2014
• First Posted: September 4, 2014
• Study Start: July 23, 2014
• Primary Completion: July 4, 2018
• Study Completion: February 18, 2020
• Last Updated: March 18, 2020

Record last verified: 2020-03

Locations

FR (2)