Improving Retreatment Success (IMPRESS)

Phase 1

Completed

Conditions: Recurrent Tuberculosis

Interventions: Drug: moxifloxacin

Registration Number: NCT02114684

Lead Sponsor: Centre for the AIDS Programme of Research in South Africa

Brief Summary: This is an open label randomized controlled clinical trial comparing two regimens for treatment of smear-positive pulmonary TB, among patients previously treated for TB. The primary objective is to determine if a moxifloxacin-containing regimen, substituting moxifloxacin for ethambutol, of 24 weeks duration is superior to a control regimen of 24 weeks duration in improving treatment outcomes in patients with recurrent TB and shortens the duration of TB treatment.

Detailed Description: Intervention Arm :12 months (6 months treatment + 12 months post treatment follow up) Control Arm :12 months (6 months treatment + 12 months post treatment follow up) Total sample size is 330.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 197

Inclusion Criteria

Adults ≥ 18 years of age
Previous history of anti-TB chemotherapy
HIV status: HIV infected and uninfected patients are allowed in the study:
All patients must agree to HIV testing to confirm HIV status.
Patients already on ARVs will be allowed in the study provided that the ART regimen is not contraindicated with any of the study agents .
HIV infected patients at any CD4 count irrespective of ART commencement and duration will be included in the study
Smear positive or Gene Xpert positive pulmonary tuberculosis
Rifampicin susceptible as determined by Gene Xpert at screening. Gene Xpert will be used to determine rifampicin resistance, hence the study team will made aware of resistance within 48 hours and prior to study enrolment.
Karnofsky score greater than 70
Female candidates of reproductive potential must agree to use two reliable methods of contraception while on study: a barrier method of contraception (condoms or cervical cap) together with another reliable form of contraceptive (condoms with a spermicidal agent, a diaphragm or cervical cap with spermicide, an Intrauterine Device (IUD), or hormone-based contraceptive)
A negative pregnancy test
Laboratory parameters done at, or 14 days prior to, screening:
- Haemoglobin level of at least 7.0 g/dL
- Serum aspartate transaminase (AST) and alanine transaminase (ALT) activity less than 3 times the upper limit of normal
- Serum total bilirubin level less than 2.5 times upper limit of normal
- Creatinine clearance (CrCl) level greater than 60 mls/min
- Platelet count of at least 50 x109cells/L
- Serum potassium greater than 3.0 mmol/L

Exclusion Criteria

Patients on a Nevirapine (NVP)-containing ART regimen at screening
Pregnant or breastfeeding
Received an antibiotic active against M. tuberculosis in the last 14 days (e.g. fluoroquinolones, macrolides, standard anti-tuberculosis drugs).
Patients with known M. tuberculosis resistance to any of the study drugs at screening
History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, or ziprasidone during the intensive phase of tuberculosis treatment.
Known allergies or intolerance to any of the study drugs.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Moxifloxacin	moxifloxacin	A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol, daily for 24 weeks, see information below. Intensive phase 7 days a week for 8 weeks Continuation phase - 7 days a week for 16 weeks RH(150,75mg), Z (500mg), M (400mg) Dosage and number of tablets dispensed is dependent on participants weight band.
Ethambutol	moxifloxacin	An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), daily for 24 weeks duration, substituting Ethambutol for Moxifloxacin. Intensive phase 7 days a week for 8 weeks Continuation phase - 7 days a week for 16 weeks.See details below. (150,75,400,275 mg) RHZE Dosage and number of tablets dispensed is dependent on participants weight band.

Primary Outcome Measures

Name	Time	Method
Sputum Culture Conversion Rates at Week 8 and Month 6 Post Tuberculosis Treatment Initiation	24 weeks	The proportion of patients with negative sputum cultures at the end of the intensive phase (8 weeks) and the proportion of patients with negative sputum cultures at 6 months were compared between the two study arms. All participants with sputum culture results at week 8 and month 6 were included in the analysis.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events and 8-week Culture Conversion Rates Among HIV-infected Patients vs. HIV-uninfected Patients	up to 2 years for adverse events and 8 weeks for culture conversion rates	To compare adverse events and 8-week culture conversion rates among HIV-infected patients vs. HIV-uninfected patients. The proportion of participants with at least one grade 3 or 4 adverse event was measured.
Proportion of Patients With Unfavourable Outcomes or Tuberculosis Recurrence in the Moxifloxacin and Control Arm.	up to 2 years	A patient was defined as having an unfavourable outcome if he/she was not cured at the end of treatment or did not successfully complete treatment. Recurrence after completion of treatment was defined as two positive cultures within a period of four months without an intervening negative culture.
Time to Culture-conversion of the Moxifloxacin Regimen and the Ethambutol Regimen	Up to 2 years	To determine the time to culture-conversion of the moxifloxacin regimen and the ethambutol regimen.
Proportion of Patients With Any Grade 3 or 4 Adverse Reactions in the Two Study Arms	Up to 2 years	To compare the proportion of patients with any Grade 3 or 4 adverse reactions in the two study arms. Outcome measured in terms of number of participants with at least one grade 3 or 4 events, and not in number of events.