Fibrocavitary pulmonary disease caused by M.avium complex
Conditions
Interventions
Trade Name: Lamprene
Pharmaceutical Form: Capsule
Trade Name: Rifadin
Product Name: Rifampicin
Product Code: RVG 116777//08702
Pharmaceutical Form: Tablet
INN or Proposed INN: RIFAMPICIN
CAS Number:
Sponsors
Radboudumc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - ATS diagnostic criteria for fibro-cavitary MAC-PD met, i.e. symptomatic, fibro-cavitary lesions seen on X-ray or (HR)CT scan of the lungs and =2 positive cultures of the same M. avium complex species (Griffith et al., 2007). - At least one of the positive cultures must be done in the last 4 months before inclusion. - Age > 18 years. - Signed and dated patient informed consent. - Patients can be included in spite of previous treatment if treatment was conform ATS-guidelines and they did not receive any treatment in the last 2 months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 62 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 62
Exclusion criteria
Exclusion criteria: - Extensive cavitary MAC-PD defined as cavitary lesions in two or more lobes with the smallest cavity having a diameter >3 centimetre, measured from Computed Tomography (CT) images or when physician deems it favourable to treat the patient with additional amikacine - Macrolide-resistant MAC strain isolated at the time of diagnosis. - A relevant medical history or current condition that might interfere with drug absorption, distribution, metabolism or excretion. - Use of concomitant drugs that interfere with the pharmacokinetics of the study drugs. - HIV infected. - Diagnosed with cystic fibrosis. - Pregnant or breastfeeding or inadequate contraceptive measures (if applicable). - ALAT > 3 times the upper limit of normal. - ASAT > 3 times the upper limit of normal. - An abnormal serum creatinine level (defined as a level that is higher than the upper limit of normal). - Active pulmonary malignancy (primary or metastatic) or any other malignancy requiring chemotherapy or radiotherapy within 1 year before screening or anticipated during the study period. - Use of drugs for co-morbid conditions that have interactions with any of the drugs in the study and that cannot be safely exchanged for an alternative drug for which such interactions are not known to occur. - Active alcohol abuse. - Hypersensitivity to one of the study drugs. - Patients with previous failure of treatment for MAC-PD, defined as persistent culture positivity despite >6 months of guideline-recommended treatment. - Patients who need to stop treatment for more then 15 consecutive days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of two different recommended treatment regimens for MAC-PD (rifampicin-ethambutol-azithromycin vs clofazimine-ethambutol-azithromycin), as measured by the percentage of patients that has converted to negative cultures after 6 months of treatment in each arm.;Secondary Objective: 1) Percentage of patients showing sputum culture conversion at 1, 2 and 4 months (which treatment arm shows the fastest conversion). 2) The differences in radiological outcomes. 3 The tolerability of the study drugs, measured by the percentage of patients with adverse events and the percentage of patients that deviate from protocol. 4) Differences in patient-reported health status after 6 months of treatment (St. George’s Respiratory Questionnaire (SGRQ) 5) The difference in lung function parameters: FEV1 (L), FVC (L), IC (L), FRC (L), TLC (L), 6 minute walking distance (6MWD). 6) To describe the pharmacokinetics of rifampicin, clofazimine, ethambutol and azithromycin. 7) To correlate the pharmacokinetics of the individual drugs to adverse events 8) To correlate pharmacokinetics to pharmacodynamics ( culture conversion) after 1,2,4,6 months of treatment. ;Primary end point(s): Sputum culture conversion after 6 months of treatment;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Sputum culture conversion at 1, 2 and 4 months (which treatment arm shows the fastest conversion). 2. The differences in radiological outcome. 3. The percentage of patients having adverse events related to study drugs and the percentage of patients that deviate from protocol. 4. Differences in patient-reported health status after 6 months of treatment (St. George’s Respiratory Questionnaire (SGRQ) 5. Difference in lung function parameters: FEV1 (L), FVC (L), IC (L), FRC (L), TLC (L), 6 minute walking distance (6MWD). 6. Area under the time-concentration curve (AUC) and peak serum concentration (Cmax) at 1 month and 4 months for clofazimine, rifampicin, ethambutol and azithromycin. 7. Correlation between pharmacokinetics and adverse events 8. Correlation between pharmacokinetics and pharmacodynamics (culture conversion) after 1,2,4,6 months of treatment. ;Timepoint(s) of evaluation of this end point: 1. 1,2 and 4 months 2. 6 months 3. 6 months 4. 6 months 5. 6 months 6. 1 and 4 months 7. 1,2,4, 6 months 8. 1,2,4, 6 months | — |
Countries
Netherlands
Contacts
Public ContactUCCZ Dekkerswald
Radboudumc
Outcome results
None listed