Clinical trial NCT02114684: Improving Retreatment Success (IMPRESS)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Recurrent Tuberculosis
Lead sponsor: Centre for the AIDS Programme of Research in South Africa
Sponsor class: NETWORK
First posted: 2014-04-15
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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.

Primary outcomes:
measure: Sputum Culture Conversion Rates at Week 8 and Month 6 Post Tuberculosis Treatment Initiation
timeFrame: 24 weeks
Secondary outcomes:
measure: Time to Culture-conversion of the Moxifloxacin Regimen and the Ethambutol Regimen
timeFrame: Up to 2 years
measure: Proportion of Patients With Any Grade 3 or 4 Adverse Reactions in the Two Study Arms
timeFrame: Up to 2 years
measure: Number of Participants With Adverse Events and 8-week Culture Conversion Rates Among HIV-infected Patients vs. HIV-uninfected Patients
timeFrame: up to 2 years for adverse events and 8 weeks for culture conversion rates
measure: Proportion of Patients With Unfavourable Outcomes or Tuberculosis Recurrence in the Moxifloxacin and Control Arm.
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Durban
country: South Africa
facility: CAPRISA eThekwini Clinical Research Site (eCRS)
state: KwaZulu Natal
Study officials:
affiliation: Centre for the AIDS Programme of Research in South Africa
name: Nesri Padayatchi, MBChB, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for the AIDS Programme of Research in South Africa
name: Kogieleum Naidoo, MBChB
role: STUDY_DIRECTOR
References:
citation: Perumal R, Padayatchi N, Yende-Zuma N, Naidoo A, Govender D, Naidoo K. A Moxifloxacin-based Regimen for the Treatment of Recurrent, Drug-sensitive Pulmonary Tuberculosis: An Open-label, Randomized, Controlled Trial. Clin Infect Dis. 2020 Jan 1;70(1):90-98. doi: 10.1093/cid/ciz152.
citation: Naidoo A, Chirehwa M, Ramsuran V, McIlleron H, Naidoo K, Yende-Zuma N, Singh R, Ncgapu S, Adamson J, Govender K, Denti P, Padayatchi N. Effects of genetic variability on rifampicin and isoniazid pharmacokinetics in South African patients with recurrent tuberculosis. Pharmacogenomics. 2019 Mar;20(4):225-240. doi: 10.2217/pgs-2018-0166. Epub 2019 Feb 15.