Clinical trial NCT01968421: Prevention of OM-85 on Bronchiectasis Exacerbation
Official title: To Investigate the PRevention of OM-85 on Bronchiectasis Exacerbation (iPROBE): a Multicenter, Randomised, Double-dummy, Placebo-controlled Clinical Trial in Chinese Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bronchiectasis With Acute Exacerbation
Keywords: OM-85, bronchiectasis, placebo, acute exacerbation
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
Collaborators: name: Peking University
name: Capital Medical University
name: Tianjin Medical University
name: Zhejiang University
name: China Medical University, China
name: Tongji University
name: Wenzhou Medical University
First posted: 2013-10-24
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Non-cystic fibrosis bronchiectasis is characterized by irreversible dilatation of the medium-sized bronchi as a result of airway injury due to recurrent or chronic inflammation and infection. Bronchiectasis airways are often colonized with bacterial species. Infections of the airways are thought to play an important role in bronchiectasis exacerbation. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing scientific interest. OM-85, consisting extracts of eight kinds of bacteria important in respiratory infections, has shown the benefit for significantly reducing the incidence of exacerbations of chronic obstructive pulmonary disease (COPD). The purpose of this study is to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE).

This study is designed as a prospective randomised double-blind placebo-controlled multi-centred trial.

Detailed description: Bronchiectasis is still a common chronic respiratory disease. Non-cystic fibrosis bronchiectasis is characterized by irreversible dilatation of the medium-sized bronchi as a result of airway injury due to recurrent or chronic inflammation and infection. Clinical features of bronchiectasis include chronic production of sputum often mucopurulent or purulent in nature, persistent bacterial colonization, recurrent lower respiratory tract infections. Bronchiectasis airways are often colonized with bacterial species. Infections of the airways are thought to play an important role in bronchiectasis exacerbation. Progressive lung damage in bronchiectasis results from a 'vicious cycle' of recurrent bacterial infection and a deregulated inflammatory response. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing scientific interest. OM-85, consisting extracts of eight kinds of bacteria important in respiratory infections, has been known to support the respiratory tract resistance to the pathogens via activating pulmonary macrophages, increasing the ratio of CD4 to CD8 lymphocytes, and changing the level of a variety of cytokines in the lung. OM-85 has shown the benefit for significantly reducing the incidence of exacerbations of chronic obstructive pulmonary disease (COPD). Bronchiectasis exacerbations contribute substantially to rapid decline in lung function, reduced quality of life, and the medical costs. The purpose of this study is to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE).

This study is designed as a prospective randomised double-blind placebo-controlled multi-centred trial. A total of 244 patients with bronchiectasis, who have had at least one exacerbation of bronchiectasis in the previous year, will be included. The subjects will be randomly received two courses of 7mg of OM-85 or matching placebo to take one oral capsule per day for 10 days a month for 3 consecutive months at the beginning of the study, then 3 months later with the same schedule for 1 year.

We will investigate whether long-term therapy with an oral immunostimulant OM-85 can decrease exacerbations in patients with bronchiectasis over 1-year period. Besides, we will assess other outcomes including: the rate of event-based exacerbation, lung function parameters, the total scores on the St George's respiratory questionnaire and coughing, and inflammatory index. We hope that this study will provide novel information on the preventive effects of OM-85 treatment on bronchiectasis exacerbation and will address a knowledge gap for this poorly understood and under-studied disease.

Eligibility criteria: Inclusion Criteria:

* An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject. The Informed Consent form will be signed.
* Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule or medication intake according to the judgment of the investigator.
* Subject with both genders is adult patients (\>18 years) diagnosed with bronchiectasis by high-resolution computed tomography (HRCT) of chest within 3 years of study inclusion having had at least 1 acute exacerbation in the previous year when recruiting.

Exclusion Criteria:

* History of cystic fibrosis;
* Hypogammaglobulinaemia;
* Allergic bronchopulmonary aspergillosis;
* Active tuberculosis;
* Subject has been assigned to treatment in a study of the medication under investigation in this study in the previous 6 months.
* Subject has a history of chronic alcohol or drug abuse within the last 6 months.
* Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study.
* Subject has a known hypersensitivity to any components of OM85.
* Recent immunostimulant in last 3 months, cancer, stroke, severe cardiovascular disease, hepatic/kidney impairment, active TB, immuno-related diseases (RA and inflammatory bowel diseases), active ABPA.
* Subjects are free to withdraw from the study at any time, without prejudice to their continued care.
* Subject develops an illness that would interfere with his/her continued participation.
* Subject is noncompliant with the study procedures or medications in the opinion of the investigator.
* Subject takes prohibited concomitant medications as defined in this protocol (flu vaccine and pneumococcal vaccine).
* Subject withdraws his/her consent.
* There will have a confirmation of a pregnancy during the study, as evidenced by a positive pregnancy test.
* The sponsor or a regulatory agency requests withdrawal of the subject.

Primary outcomes:
measure: Bronchiectasis Exacerbation
timeFrame: 1 year
Secondary outcomes:
measure: Life Quality
timeFrame: 1 year
measure: Lung Function
timeFrame: 1 year
Other outcomes:
measure: Rescue Medication
timeFrame: 1 year
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Shanghai
country: China
facility: Shanghai Tongji University
Study officials:
affiliation: Peking Union Medical College Hospitak
name: Jinming Gao, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gao J, Gao X, Kong L. To investigate the prevention of OM-85 on bronchiectasis exacerbations (iPROBE) in Chinese patients: study protocol for a randomized controlled trial. Trials. 2014 Apr 29;15:150. doi: 10.1186/1745-6215-15-150.