Inhaled Mannitol as a Mucoactive Therapy for Bronchiectasis

Syntara

Status and phase

Completed

Phase 3

Conditions

Bronchiectasis

Treatments

Drug: Matched control

Drug: Inhaled mannitol

Study type

Interventional

Funder types

Industry

Identifiers

NCT00669331

DPM-B-305

Details and patient eligibility

About

No gold standard therapy exists for clearing mucus from the airways of patients with bronchiectasis. While rhDNase has a proven place in the treatment of cystic fibrosis (CF), it failed to improve Forced expiratory volume in one second (FEV1) in a short-term non-CF bronchiectasis study and has been shown to be detrimental after 6 months therapy in non CF bronchiectasis, moreover it has no proven effect on mucociliary clearance. Hypertonic saline has been shown to have a comparable mode of action to inhaled mannitol, but has yet to be examined as a long term treatment option in bronchiectasis.

The purpose of this study is to examine the efficacy and safety of 52 weeks treatment with inhaled mannitol in subjects with non-cystic fibrosis bronchiectasis. Previous studies with inhaled mannitol have demonstrated improvement in mucociliary clearance; mucus rehydration; improvement in quality of life and respiratory symptoms in patients with bronchiectasis and pulmonary function in cystic fibrosis. The results of this current study in combination with a recently completed 3 month study seek to confirm these early findings and to extend the evidence to support its use as a mucoactive therapy in subjects with bronchiectasis.

We hypothesize that mannitol will improve the overall health and hygiene of the lung through regular and effective clearing of the mucus load. As a consequence of the reduction in mucus load and inflammatory process, the frequency of bronchiectasis related pulmonary exacerbations and the need for exacerbation related antibiotic treatment should fall. Days in hospital and community health care costs are expected to change in line with improvements in respiratory health.

Finally, we plan to demonstrate that inhaled mannitol is safe and well tolerated over a 52 week period. We will test these hypotheses using 400 mg mannitol twice daily (BD) against control.

Enrollment

485 patients

Sex

All

Ages

18 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Have given written informed consent to participate in this study in accordance with local regulations
Have documented evidence of confirmed diagnosis of (non-cystic fibrosis) bronchiectasis by computed tomography (CT), High resolution computed tomography (HRCT) or bronchogram
Be aged 18 - 85 years inclusive, male and female
Have FEV1 (Forced expiratory volume in one second) ≥ 40% and ≤85% predicted* and ≥1.0L (*according to NHANES III predicted tables) measured at Visit 0A (V0A)
Clinician documented history of at least 2 pulmonary exacerbations, each requiring antibiotic therapy, in the last 12 months prior to Visit 0A (V0A) and a total of at least 4 in the last 2 years prior to Visit 0A
Have a total SGRQ (St George's respiratory questionnaire) score of ≥30 at Visit 0B (V0B)
Have a production of ≥10g of sputum at Visit 0B Have reported chronic sputum production of ≥1 tablespoon (15mL) per day on the majority of days in the 3 months prior to Visit 0A
Be able to perform all the techniques necessary to measure lung function
Have FEV1 ≥40% predicted* and ≥1.0L (*according to NHANES III 1999 predicted tables) measured at V0B (Baseline result prior to MTT (Mannitol Tolerance Test) administration)

Exclusion Criteria

Be investigators, site personnel directly affiliated with this study, or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biologically or legally adopted.
Have bronchiectasis as a consequence of cystic fibrosis or focal endobronchial lesion or otherwise curable causes (e.g. foreign body aspiration)
Be considered "terminally ill" or listed for transplantation
Be using hypertonic saline in the 14 days prior to commencing Visit 0B or thereafter at any time during the study
Have previously used inhaled mannitol (Bronchitol) for more than a day
Have had a significant episode of hemoptysis (>60 mL) in the previous 6 months
Have had rescue antibiotics in the 4 weeks prior to V0B (chronic background antibiotic therapy accepted)
Have smoked within the last 3 months and must not smoke during their participation in the study
Have had a myocardial infarction in the three months prior to Visit 0A
Have had a cerebral vascular accident in the three months prior to Visit 0A
Have had major ocular surgery in the three months prior to Visit 0A
Have had major abdominal, chest or brain surgery in the three months prior to Visit 0A
Have a known cerebral, aortic or abdominal aneurysm
Have actively treated Mycobacterium tuberculosis
Have actively treated or unstable nontuberculous mycobacterial (NTM)infection or be under consideration for NTM treatment in the next 12 months
Have unstable Allergic bronchopulmonary aspergillosis (ABPA) requiring steroid therapy (≤5mg dose oral steroids in stable ABPA accepted)
Have end stage interstitial lung disease
Have active malignancy including melanoma (other skin carcinomas exempted). Remissions from any malignancy ≥2 years also exempted
Be breast feeding or pregnant, or plan to become pregnant while in the study
Be using an unreliable form of contraception (female subjects at risk of pregnancy only)
Be participating in another investigational drug study, parallel to, or within 4 weeks of Visit 0A
Have a known intolerance to mannitol or β2-agonists
Have uncontrolled hypertension - e.g. for adults: systolic blood pressure (BP) > 190 and or diastolic BP > 100
Subject has a condition or is in a situation which in the Investigator's opinion may put the subject at significant risk, may confound results or may interfere significantly with the patient's participation in the study
Have previously been screen failed for the study (exceptions - see section 3.3.2 Eligibility Criteria - Rescreening)