A randomized controlled trial on hypertonic saline inhalation in patients with nodular-bronchiectatic Mycobacterium avium complex pulmonary disease

Nontuberculous mycobacteria (NTM), M. tuberculosis and M. leprae all belong to
the genus Mycobacterium. NTM comprise of 200 environmental species with a wide
variety in pathogenicity. They often manifest as pulmonary infections in people
with a predisposing immunological disorder or lung disease (e.g. asthma, COPD,
bronchiectasis). The most prevalent causative species of NTM pulmonary disease
(NTM-PD) is M. avium complex. Two major radiological disease patterns are
observed: nodular-bronchiectatic (often mild) and fibrocavitary (often severe)
disease.
The current treatment consists of long-lasting multi-drug antibiotic regimens
with suboptimal outcomes and frequent adverse drug reactions.
Hypertonic saline inhalation is a non-invasive treatment with proven efficacy
and safety in patients with cystic fibrosis and bronchiectasis and with
positive clinical experience in NTM patients. In some patients, treatment with
hypertonic saline inhalation can prevent the need for antibiotics and reduce
the burden of symptoms.

To determine the effect of hypertonic saline inhalation and best supportive
care versus best supportive care alone on clinical efficacy measures in
patients with nodular-bronchiectatic M. avium complex pulmonary disease, as
measured by changes in the Quality of Life-Bronchiectasis with NTM module
(QOL-B-NTM) and PROMIS Fatigue Short Form Score questionnaires.

Open-label, randomized, two-arm controlled pilot study
Intervention arm: hypertonic saline inhalation plus best supportive care
Control arm: best supportive care

Hypertonic Saline Inhalation (Hyaneb); inhalation of 5ml of 5.8% NaCl two times
a day

This pilot study is largely embedded in the regular patient care.
The following activities require an additional study-related burden for ALL
participants:
- Randomisation to a study-arm
- Filling in the QoL-B + NTM module and PROMIS Fatigue Short Form
questionnaires at 0, 4,8 and 12 weeks.
- Filling in the NCSI after 12 weeks.
- Filling in the adverse device effects diary during the first 2 weeks on
therapy
- 6 and 12 months after finishing the treatment we will ask the patient (either
during a regular out-patient follow-up visit or telephone interview in case a
patient is referred back to another physician) what their symptoms are, what
treatment they are receiving (hypertonic saline, antibiotics or otherwise),
whether they are satisfied with this treatment, if any side effects are present
and if they have obtained sputum culture conversion.

The following activities require an additional study-related burden for
patients in the intervention arm:
- 2 additional telephone interviews after 4 and 8 weeks
- Maximal 1 live visit to clinic after 4 weeks, in case the telephone interview
is not preferred or if severe side-effects.are present
- Filling in the therapy adherence questionnaire on a weekly basis during 12
weeks.

The following activities require an additional study-related burden for
patients in the control arm:
- 3 telephone interviews after 2,4 and 8 weeks
- Maximal 1 live visit to clinic after 4 weeks, in case the telephone interview
is not preferred or if severe side-effects.are present


The study related risk is the postponing of hypertonic saline for patients in
the control arm for 12 weeks. This is an acceptable risk since
nodular-bronchiectatic M. avium complex lungdisease progresses slowly and is
not expected to deteriorate during 12 weeks.