Study protocol: a randomized, double-blind, parallel, two-arm, placebo control trial investigating the feasibility and safety of immunoglobulin treatment in COPD patients for prevention of frequent recurrent exacerbations

Juthaporn Cowan, Sunita Mulpuru, Shawn Aaron, Gonzalo Alvarez, Antonio Giulivi, Vicente Corrales-Medina, Venkatesh Thiruganasambandamoorthy, Kednapa Thavorn, Ranjeeta Mallick, D William Cameron, Juthaporn Cowan, Sunita Mulpuru, Shawn Aaron, Gonzalo Alvarez, Antonio Giulivi, Vicente Corrales-Medina, Venkatesh Thiruganasambandamoorthy, Kednapa Thavorn, Ranjeeta Mallick, D William Cameron

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a chronic progressive inflammatory disease of the airways, associated with frailty, disability, co-morbidity, and mortality. Individuals with COPD experience increased risk and rates of acute exacerbation as their lung disease worsens. Current treatments to prevent acute exacerbation of COPD (AECOPD) are only modestly effective. New therapies are needed to improve the quality of life and clinical outcomes for individuals living with COPD and especially for those prone to frequent recurrent AECOPD. Recent research has suggested an association of gammaglobulin or immunoglobulin G levels with AECOPD and a favorable effect of an immunoglobulin treatment on the frequency of recurrent AECOPD, healthcare provider visits, treatments, and hospitalizations. However, control trials are required to confirm this apparent association and therapeutic effect. This study aims to assess if intravenous immunoglobulin (IVIG) therapy is feasible, safe, tolerable, and potentially effective in reducing the frequency of recurrent AECOPD.

Methods/design: Adult COPD patients at The Ottawa Hospital (TOH) will be recruited to partake in a randomized double-blind, parallel, two-arm, placebo control trial. Eligible patients will be administered either IVIG or normal saline following 1:1 randomization and every 4 weeks for 1 year. The primary outcome of feasibility will be determined by recruitment, patient adherence, safety and tolerance, success of the follow-up procedures, and outcome measurement. The safety and tolerability will be assessed through adverse events, adherence, and study withdrawals. Efficacy trends will be investigated by assessing incidence rates of AECOPD, improvement in quality of life, and healthcare services use and cost.

Discussion: The study results will inform larger studies designed to confirm a clinically significant therapeutic effect in identifiable populations which would be a major advance in the care of COPD patients.

Trial registration number: ClinicalTrial.gov, NCT03018652 and NCT02690038.

Keywords: COPD; COPD exacerbation; Feasibility and safety; Immunoglobulin; Pilot study; Randomized clinical trial.

Conflict of interest statement

The study protocol was approved by the OHRI Research Ethics Board (protocol number 20150925-01H, 20160077-01H and 20170005-01H). Not applicable The authors declare that they have no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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