search
Back to results

Improving Retreatment Success (IMPRESS) (IMPRESS)

Primary Purpose

Recurrent Tuberculosis

Status
Completed
Phase
Phase 1
Locations
South Africa
Study Type
Interventional
Intervention
moxifloxacin
Sponsored by
Centre for the AIDS Programme of Research in South Africa
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Recurrent Tuberculosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • CAPRISA eThekwini Clinical Research Site (eCRS)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Moxifloxacin

Ethambutol

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Time to Culture-conversion of the Moxifloxacin Regimen and the Ethambutol Regimen
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
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.
Number of Participants With Adverse Events and 8-week Culture Conversion Rates Among HIV-infected Patients vs. HIV-uninfected Patients
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.
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.

Full Information

First Posted
January 29, 2014
Last Updated
June 11, 2019
Sponsor
Centre for the AIDS Programme of Research in South Africa
search

1. Study Identification

Unique Protocol Identification Number
NCT02114684
Brief Title
Improving Retreatment Success (IMPRESS)
Acronym
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

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
November 2013 (Actual)
Primary Completion Date
July 2017 (Actual)
Study Completion Date
July 17, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre for the AIDS Programme of Research in South Africa

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Tuberculosis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
197 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Moxifloxacin
Arm Type
Active Comparator
Arm 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.
Arm Title
Ethambutol
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
moxifloxacin
Other Intervention Name(s)
AVELON
Intervention Description
[isoniazid (H), rifampicin (R), pyrazinamide (Z), moxifloxacin (M)]
Primary Outcome Measure Information:
Title
Sputum Culture Conversion Rates at Week 8 and Month 6 Post Tuberculosis Treatment Initiation
Description
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.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Time to Culture-conversion of the Moxifloxacin Regimen and the Ethambutol Regimen
Description
To determine the time to culture-conversion of the moxifloxacin regimen and the ethambutol regimen.
Time Frame
Up to 2 years
Title
Proportion of Patients With Any Grade 3 or 4 Adverse Reactions in the Two Study Arms
Description
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.
Time Frame
Up to 2 years
Title
Number of Participants With Adverse Events and 8-week Culture Conversion Rates Among HIV-infected Patients vs. HIV-uninfected Patients
Description
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.
Time Frame
up to 2 years for adverse events and 8 weeks for culture conversion rates
Title
Proportion of Patients With Unfavourable Outcomes or Tuberculosis Recurrence in the Moxifloxacin and Control Arm.
Description
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 Frame
up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nesri Padayatchi, MBChB, MSc
Organizational Affiliation
Centre for the AIDS Programme of Research in South Africa
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kogieleum Naidoo, MBChB
Organizational Affiliation
Centre for the AIDS Programme of Research in South Africa
Official's Role
Study Director
Facility Information:
Facility Name
CAPRISA eThekwini Clinical Research Site (eCRS)
City
Durban
State/Province
KwaZulu Natal
ZIP/Postal Code
4001
Country
South Africa

12. IPD Sharing Statement

Citations:
PubMed Identifier
30809633
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.
Results Reference
derived
PubMed Identifier
30767706
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.
Results Reference
derived

Learn more about this trial

Improving Retreatment Success (IMPRESS)

We'll reach out to this number within 24 hrs