Improving Retreatment Success (IMPRESS)

Condition(s) targeted: Recurrent Tuberculosis

Intervention: moxifloxacin (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Centre for the AIDS Programme of Research in South Africa

Official(s) and/or principal investigator(s):
Nesri Padayatchi, MBChB, MSc, Principal Investigator, Affiliation: Centre for the AIDS Programme of Research in South Africa
Kogieleum Naidoo, MBChB, Study Director, Affiliation: Centre for the AIDS Programme of Research in South Africa

Overall contact:
Dhineshree Govender, MSc, Phone: +27 31 260, Ext: 1905, Email: Dhineshree.govender@caprisa.org

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.

Official title: An Open Label Randomized Controlled Clinical Trial Comparing a 24Week Oral Regimen Containing Moxifloxacin With a 24 Week Standard Drug Regimen for the Treatment of Smear-positive Pulmonary Tuberculosis in Patients Previously Treated for TB

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome: A moxifloxacin-containing regimen, substituting moxifloxacin for ethambutol, is superior to a control regimen in improving treatment outcomes

Secondary outcome:

1.Time to culture-conversion of the moxifloxacin regimen and the ethambutol regimen using data from 2-, 4-, 6-, and 8-week cultures

Compare the proportion of patients with any Grade 3 or 4 adverse reactions

Compare adverse events and 2-month culture conversion rates among HIV-infected patients vs. HIV-uninfected patients

Compare the rates of treatment failure and recurrence of the intervention and control arm.

Detailed description: Intervention Arm :12 months (6 months treatment + 6 months post treatment follow up) Control Arm :12 months (8 months treatment + 6 months post treatment follow up) Total sample size is 330.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Dhineshree Govender, MSc, Phone: +27 31 260, Ext: 1905, Email: Dhineshree.govender@caprisa.org

CAPRISA eThekwini Clinical Research Site (eCRS), Durban, KwaZulu Natal 4001, South Africa; Recruiting
Dhineshree Govender, MSc, Phone: +27 31 260, Ext: 1905, Email: Dhineshree.govender@caprisa.org
Rochelle N Adams, MBBCh, Sub-Investigator
Aveshen Govender, MBChB, Sub-Investigator
Shanisa Naidoo, MBChB, Sub-Investigator
Tilagavathy Chinappa, MBChB, Sub-Investigator

Starting date: November 2013
Last updated: July 27, 2015