To investigate the prevention of OM-85 on bronchiectasis exacerbations (iPROBE) in Chinese patients: study protocol for a randomized controlled trial

Jinming Gao, Xiang Gao, Lingfei Kong, Jinming Gao, Xiang Gao, Lingfei Kong

Abstract

Background: Non-cystic fibrosis bronchiectasis is characterized by the irreversible dilatation of the medium-sized bronchi as a result of airway injury from recurrent or chronic inflammation and lower respiratory tract infections. Bronchiectasis airways are commonly colonized with bacterial species. Infections of the airways play important role in bronchiectasis exacerbations. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing interest. OM-85, consisting of extracts of eight kinds of bacteria important in respiratory infections, could support the respiratory tract resistance to the pathogens. OM-85 has been shown to be a benefit by decreasing the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) in several perspective clinical trials. Exacerbation of bronchiectasis substantially contributes to a more rapid decline in lung function, reduced quality of life, and healthcare costs. In this context, we plan to conduct a clinical trial to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE).

Methods/design: This study is designed as a prospective, randomized, double blind, placebo-controlled multicenter 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 randomly receive two courses of 7 mg of OM-85 or a matching placebo. The treatment dose of OM-85 will be one daily capsule taken orally for 10 days each month for 3 consecutive months at the beginning of the study, followed by 3 months of no drug. This schedule will repeat until the patient has been seen for one year.

Discussion: We will investigate whether long-term treatment with an oral immunostimulant (OM-85) could decrease exacerbations of bronchiectasis over a one-year period. We will also assess other relevant outcomes, including the rate of event-based exacerbation, lung function parameters, and total scores judged by the St George's respiratory questionnaire, Leicester cough questionnaire, and inflammatory index. We hope that this study will provide new information on the preventive effects of OM-85 on bronchiectasis exacerbations and will address a knowledge gap for this understudied disease.

Trial registration: This study is registered at http://www.clinicaltrials.gov (identifier NCT01968421) on 19 October 2013.

Figures

Figure 1
Figure 1
Flow chart of the patients through the clinical trial. BV: broncho-vaxom (OM-85).
Figure 2
Figure 2
Treatment periods and visits.

References

    1. Karadag B, Karakoc F, Ersu R, Kut A, Bakac S, Dagli E. Non-cystic-fibrosis bronchiectasis in children: a persisting problem in developing countries. Respiration. 2005;72(3):233–238. doi: 10.1159/000085362.
    1. O'Donnell AE. Bronchiectasis. Chest. 2008;134(4):815–823. doi: 10.1378/chest.08-0776.
    1. Pasteur MC, Bilton D, Hill AT. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010;65:577. doi: 10.1136/thx.2010.142778.
    1. De Soyza A, Brown JS, Loebinger MR. Research priorities in bronchiectasis. Thorax. 2013;68:695–696. doi: 10.1136/thoraxjnl-2012-202893.
    1. Seitz AE, Olivier KN, Adjemian J, Holland SM, Prevots R. Trends in bronchiectasis among medicare beneficiaries in the United States, 2000 to 2007. Chest. 2012;142(2):432–439.
    1. Whitters D, Stockley R. Immunity and bacterial colonisation in bronchiectasis. Thorax. 2011;67(11):1006–1013.
    1. Chalmers JD, Hill AT. Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis. Mol Immunol. 2013;55(1):27–34. doi: 10.1016/j.molimm.2012.09.011.
    1. Altenburg J, de Graaff CS, van der Werf TS, Boersma WG. Immunomodulatory effects of macrolide antibiotics - part 2: advantages and disadvantages of long-term, low-dose macrolide therapy. Respiration. 2011;81(1):75–87. doi: 10.1159/000320320.
    1. Wong C, Jayaram L, Karalus N, Eaton T, Tong C, Hockey H, Milne D, Fergusson W, Tuffery C, Sexton P, Storey L, Ashton T. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):660–667. doi: 10.1016/S0140-6736(12)60953-2.
    1. Fennelly KP, Griffith DE. Azithromycin in non-cystic-fibrosis bronchiectasis. Lancet. 2013;381(9860):27.
    1. Chalmers JD, Smith MP, McHugh BJ, Doherty C, Govan JR, Hill AT. Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2012;186(7):657–665. doi: 10.1164/rccm.201203-0487OC.
    1. Anthonisen NR. OM-8BV for COPD. Am J Respir Crit Care Med. 1997;156(6):1713–1714. doi: 10.1164/ajrccm.156.6.ed15-97.
    1. Collet JP, Shapiro P, Ernst P, Renzi T, Ducruet T, Robinson A. The PARI-IS Study Steering Committee and Research Group. Prevention of Acute Respiratory Infection by an Immunostimulant. Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1997;156(6):1719–1724. doi: 10.1164/ajrccm.156.6.9612096.
    1. Soler M, Mutterlein R, Cozma G. Double-blind study of OM-85 in patients with chronic bronchitis or mild chronic obstructive pulmonary disease. Respiration. 2007;74(1):26–32. doi: 10.1159/000093933.
    1. Mackley R. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis. Thorax. 2013;68:866. doi: 10.1136/thoraxjnl-2012-202848.
    1. O'Donnell AE, Barker AF, Ilowite JS, Fick RB. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. rhDNase Study Group. Chest. 1998;113(5):1329–1334. doi: 10.1378/chest.113.5.1329.
    1. Little RJ, D'Agostino R, Cohen ML, Dickersin K, Emerson SS, Farrar JT, Frangakis C, Hogan JW, Molenberghs G, Murphy SA, Neaton JD, Rotnitzky A, Scharfstein D, Shih WJ, Siegel JP, Stern H. The prevention and treatment of missing data in clinical trials. N Engl J Med. 2012;367(14):1355–1360. doi: 10.1056/NEJMsr1203730.
    1. Martinez-Garcia MA, Soler-Cataluna JJ, Donat Sanz Y, Catalan Serra P, Agramunt Lerma M, Ballestin Vicente J, Perpina-Tordera M. Factors associated with bronchiectasis in patients with COPD. Chest. 2011;140(5):1130–1137. doi: 10.1378/chest.10-1758.
    1. Chang AB, Grimwood K, Robertson CF, Wilson AC, van Asperen PP, O'Grady KA, Sloots TP, Torzillo PJ, Bailey EJ, McCallum GB, Masters IB, Byrnes CA, Chatfield MD, Buntain HM, Mackay IM, Morris PS. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial. Trials. 2012;13:156. doi: 10.1186/1745-6215-13-156.
    1. Nick JA, Moskowitz SM, Chmiel JF, Forssen AV, Kim SH, Saavedra MT, Saiman L, Taylor-Cousar JL, Nichols DP. Azithromycin May Antagonize Inhaled Tobramycin when Targeting Pseudomonas aeruginosa in Cystic Fibrosis. Ann Am Thorac Soc. 2014;11:342–350.
    1. Murray MP, Govan JR, Doherty CJ, Simpson AJ, Wilkinson TS, Chalmers JD, Greening AP, Haslett C, Hill AT. A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2011;183(4):491–499. doi: 10.1164/rccm.201005-0756OC.
    1. Chang AB, Bilton D. Exacerbations in cystic fibrosis: 4–Non-cystic fibrosis bronchiectasis. Thorax. 2008;63(3):269–276. doi: 10.1136/thx.2006.060913.
    1. Murray MP, Turnbull K, MacQuarrie S, Pentland JL, Hill AT. Validation of the Leicester Cough Questionnaire in non-cystic fibrosis bronchiectasis. Eur Respir J. 2009;34(1):125–131. doi: 10.1183/09031936.00160508.

Source: PubMed

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