To determine the effectiveness of the currently recommended treatment regimens.
ID
Source
Brief title
Condition
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the percentage of patients that has converted to
negative sputum cultures after 6 months of antibiotic treatment.
Secondary outcome
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.
Background summary
Pulmonary disease caused by Mycobacterium avium complex is emerging in the
Netherlands, particularly among patients with chronic obstructive pulmonary
disease. Since very few clinical trials have been performed, the optimal
antibiotic treatment for these infections is unknown. Different treatment
recommendations have been issued, none of which have been compared in clinical
trials.
Study objective
To determine the effectiveness of the currently recommended treatment regimens.
Study design
Open label randomized clinical trial. In this study we compare two regimens
that are being used in daily clinical practice
(rifampicine-ethambutol-azithromycin and clofazimine-ethambutol-azithromycin).
Patients will have a follow up of 6 months during this trial.
Intervention
One group receives the regimen recommended by the American Thoracic Society
(azithromycin, rifampicin and ethambutol) and one group receives the regimen
recommended by Canadian investigators (azithromycin, clofazimine and
ethambutol).
Study burden and risks
The diagnostic interventions in the study groups proposed are part of normal
clinical practice. The antibiotics used in the treatment arms have shown
efficacy in a clinical trial and case series, the antibiotics are thus used for
a known indication.
Geert Grootplein 10
Nijmegen 6525 GA
NL
Geert Grootplein 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- ATS diagnostic criteria for nodular bronchiectatic or fibro-cavitary MAC-PD met, i.e. symptomatic, fibro-cavitary lesions, bronchiectasis or nodules 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.
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; this is only applicable if these others drugs lower one of study drugs or cause safety issues; such as medication that causes QTc interval prolongation; such as bedaquiline, antidepressants, antiarrhythmics or fluoroquinolones, voriconazole, protease inhibitors
- 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2015-003786-28 |
| EudraCT | EUCTR2015-003786-28-NL |
| CCMO | NL54916.091.15 |