Improving Retreatment Success (IMPRESS)

NCT02114684 | Completed Phase 1 Results

• 1 other identifier: CAP 011
• Study Type: interventional
• Target: 197
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Sputum Culture Conversion Rates at Week 8 and Month 6 Post Tuberculosis Treatment Initiation

  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.

  24 weeks

Secondary Outcomes (4)

• Time to Culture-conversion of the Moxifloxacin Regimen and the Ethambutol Regimen

  Up to 2 years

• Proportion of Patients With Any Grade 3 or 4 Adverse Reactions in the Two Study Arms

  Up to 2 years

• 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

• Proportion of Patients With Unfavourable Outcomes or Tuberculosis Recurrence in the Moxifloxacin and Control Arm.

  up to 2 years

Study Arms (2)

Moxifloxacin

ACTIVE COMPARATOR

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.

Drug: moxifloxacin

Ethambutol

ACTIVE COMPARATOR

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.

Drug: moxifloxacin

Interventions

moxifloxacin DRUG

\[isoniazid (H), rifampicin (R), pyrazinamide (Z), moxifloxacin (M)\]

Also known as: AVELON

Ethambutol; Moxifloxacin

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre for the AIDS Programme of Research in South Africa: lead

Study Sites (1)

CAPRISA eThekwini Clinical Research Site (eCRS)

Durban, KwaZulu-Natal, 4001, South Africa

Location

Related Publications (3)

• Rambaran S, Maseko TG, Lewis L, Hassan-Moosa R, Archary D, Ngcapu S, Garrett N, McKinnon LR, Padayatchi N, Naidoo K, Sivro A. Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection. BMC Immunol. 2023 Jul 21;24(1):21. doi: 10.1186/s12865-023-00558-z.

  PMID: 37480005 DERIVED

• 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.

  PMID: 30809633 DERIVED

• 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.

  PMID: 30767706 DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

Moxifloxacin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Mrs Nonhlanhla Yende-Zuma
• Organization: CAPRISA

Nonhlanhla.Yende@caprisa.org

0027312604392

Study Officials

• Nesri Padayatchi, MBChB, MSc

  Centre for the AIDS Programme of Research in South Africa

  PRINCIPAL INVESTIGATOR

• Kogieleum Naidoo, MBChB

  Centre for the AIDS Programme of Research in South Africa

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: January 29, 2014
• First Posted: April 15, 2014
• Study Start: November 1, 2013
• Primary Completion: July 1, 2017
• Study Completion: July 17, 2017
• Last Updated: August 5, 2019
• Results First Posted: August 5, 2019

Record last verified: 2019-06

Locations

ZA (1)