Mycobacterium abscessus pulmonary disease MedDRA version: 20.1 Level: PT Classification code 10064789 Term: Mycobacterium abscessus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Amikacin
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Amikacin
CAS Number: 37517-28-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Conc
Sponsors
University of Queensland
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Intervention Programs Inclusion Criteria Eligible participants with mixed NTM infections (slow growers + MABS) or with recurrence of MABS infection following completion of previously successful treatment defined as remaining free of positive respiratory cultures for MABS over 12 months post treatment, will be eligible if they met the inclusion criteria listed below: 1. Positive MABS-PD diagnosis meeting all three American Thoracic Society clinical, radiological and microbiological diagnostic criteria for MABS-PD. Defined as; a. Clinical: Pulmonary symptoms and exclusion of other diagnoses. b. Radiological: Nodular or cavitary opacities on chest radiograph or a chest high-resolution computed tomography (HRCT) scan showing multifocal bronchiectasis with multiple small nodules. c. Microbiological: MABS positive culture results from at least two separate expectorated sputum samples, Or; d. Positive culture results from at least one bronchial wash or lavage, Or; e. Transbronchial or other lung biopsy with mycobacterial histopathologic features (granulomatous inflammation or acid-fast bacilli (AFB)) and positive culture for NTM or biopsy showing mycobacterial histopathologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washes that are culture positive for NTM. 2. Male or female participants in Denmark aged 18 years and older, in other countries children are included. 3. Participant has not received treatment for MABS-PD in the 12 months preceding assessment of eligibility. 4. Informed consent signed by participant or parent/legal guardian if participant is under 18 years of age. 5. Ability to comply with study visits, therapies and study procedures as judged by the site investigator. Observational Cohort Inclusion Criteria 1- Male and female participants of any age with at least one positive respiratory culture for MABS. 2- Informed consent signed by participant or parent/legal guardian if participant is under 18 years of age. 3- Ability to comply with study visits and study procedures as judged by the site investigator. Potential participants are eligible for the Intervention program (above) if the criteria below Are the trial subjects under 18? yes Number of subjects for this age range: 40 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: Intervention Program participants • Pregnant or breastfeeding • QTc interval >500 milliseconds • Received active treatment for MABS in the previous 12 months, except use of azithromycin as part of routine treatment for CF and bronchiectasis, will be excluded from the trial. Observational Cohort participants • Received active treatment for MABS in the previous 12 months, except use of azithromycin as part of routine treatment for CF and bronchiectasis, will be excluded from the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: E.2.1: To determine the probability of microbiological clearance with acceptable toxicity for treatment combinations tested inclusive of both intensive and consolidation phases for patients with MABS-PD. A1.1: SHORT INTENSIVE THERAPY Compare efficacy of intensive therapies on clearance of MABS with tolerance at 4 weeks. A1.1.1 Compare clearance of MABS with tolerance with use of inhaled amikacin and use of intravenous amikacin. A1.1.2 Compare clearance of MABS with tolerance between standard intravenous therapies given with and without clofazimine. A1.2: DURATION OF INTENSIVE THERAPY FOR PATIENTS WITH POSITIVE MABS CULTURES AFTER 4 WEEKS OF INTENSIVE: Compare clearance with tolerance at 10 weeks between those allocated to prolonged intensive therapy and to consolidation following short intensive. A1.3: CONSOLIDATION THERAPY Compare clearance with tolerance of MABS of consolidation therapy of those allocated to oral only and those allocated to oral therapy plus inhaled amikacin. ;Secondary Objective: 1. The probability of microbiological clearance of MABS irrespective of toxicity for participants according to treatment path. 2. The safety of the treatment combinations in patients with MABS. 3. The relative change in FEV1 z-score between treatment groups. 4. Change in % Bronchiectasis scored using PRAGMA in chest CTs between Day 0 (screening) and at 12 weeks and at final outcome and between those who clear and those who do not clear MABS. 5. Change in % Air Trapping scored using PRAGMA in chest CTs between Day 0 (screening) and at 12 weeks and at final outcome and between those who clear and those who do not clear MABS. 6. Change in % Disease scored using PRAGMA in chest CTs between Day 0 (screening) and at 12 weeks and at final outcome and between those who clear and those who do not clear MABS. 7. The predictive value of structural abnormalities at Day 0 (screening) CTs for sputum conversion and for progression of structural changes in relation to th | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): No Secondary End Points;Timepoint(s) of evaluation of this end point: No Secondary end points | — |
Countries
Australia, Canada, Denmark, France, Ireland, Netherlands, New Zealand, United Kingdom
Contacts
Public ContactFORMaT Trial Management Team
Queensland Health
Outcome results
None listed