Improving Retreatment Success (IMPRESS)

Centre for the AIDS Programme of Research in South Africa

Status and phase: Completed; Phase 2; Phase 1

Conditions: Recurrent Tuberculosis

Treatments: Drug: moxifloxacin

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT02114684

CAP 011

Details and patient eligibility

About

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.

Full 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.

Enrollment: 197 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

197 participants in 2 patient groups

Moxifloxacin

Active Comparator group

Description:

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.

Treatment:

Drug: moxifloxacin

Ethambutol

Active Comparator group

Description:

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.

Treatment:

Drug: moxifloxacin