A Randomized Double-Blind Placebo-Control Feasibility Trial of Immunoglobulin Treatment for Prevention of Recurrent Acute Exacerbations of COPD

Juthaporn Cowan; Sunita Mulpuru; Sara J Abdallah; Anchal Chopra; Andrew Purssell; Michaeline McGuinty; Gonzalo G Alvarez; Antonio Giulivi; Vicente Corrales-Medina; Derek MacFadden; Loree Boyle; Delvina Hasimja; Kednapa Thavorn; Ranjeeta Mallick; Shawn D Aaron; D William Cameron

doi:10.2147/COPD.S338849

A Randomized Double-Blind Placebo-Control Feasibility Trial of Immunoglobulin Treatment for Prevention of Recurrent Acute Exacerbations of COPD

Int J Chron Obstruct Pulmon Dis. 2021 Dec 3:16:3275-3284. doi: 10.2147/COPD.S338849. eCollection 2021.

Authors

Juthaporn Cowan^{1

2}, Sunita Mulpuru^{1

2}, Sara J Abdallah², Anchal Chopra³, Andrew Purssell¹, Michaeline McGuinty¹, Gonzalo G Alvarez^{1

2}, Antonio Giulivi^{2

4}, Vicente Corrales-Medina^{1

2}, Derek MacFadden^{1

2}, Loree Boyle¹, Delvina Hasimja¹, Kednapa Thavorn^{2

5

6}, Ranjeeta Mallick², Shawn D Aaron^{1

2}, D William Cameron^{1

2}

Affiliations

¹ Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
² Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
³ Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.
⁴ Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
⁵ School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada.
⁶ Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.

Abstract

Background: Observational studies suggest that immunoglobulin treatment may reduce the frequency of acute exacerbations of COPD (AECOPD).

Objective: To inform the design of a future randomised control trial (RCT) of intravenous immunoglobulin (IVIG) treatment efficacy for AECOPD prevention.

Methods: A pilot RCT was conducted. We recruited patients with COPD hospitalized for AECOPD, or from ambulatory clinics with one severe, or two moderate AECOPD in the previous year regardless of their serum IgG level. Patients were allocated in a 1:1 ratio with balanced randomisation to monthly IVIG or normal saline for 1 year. The primary outcome was feasibility defined as pre-specified accrual, adherence, and follow-up rates. Secondary outcomes included safety, tolerance, AECOPD rates, time to first AECOPD, quality of life, and healthcare costs.

Results: Seventy patients were randomized (37 female; mean age 67.7; mean FEV1 35.1%). Recruitment averaged 4.5±0.9 patients per month (range 0-8), 34 (49%) adhered to at least 80% of planned treatments, and four (5.7%) were lost to follow-up. There were 35 serious adverse events including seven deaths and one thromboembolism. None was related to IVIG. There were 56 and 48 moderate and severe AECOPD in the IVIG vs control groups. In patients with at least 80% treatment adherence, median time to first moderate or severe AECOPD was 275 vs 114 days, favoring the IVIG group (HR 0.76, 95% CI 0.3-1.92).

Conclusion: The study met feasibility criteria for recruitment and retention, but adherence was low. A trend toward more robust treatment efficacy in adherent patients supports further study, but future trials must address treatment adherence.

Trial registration number: NCT0290038, registered 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690038 and NCT03018652, registered January 12, 2017, https://clinicaltrials.gov/ct2/show/NCT03018652.

Keywords: IVIG; immunoglobulin treatment; pilot RCT; recurrent AECOPD.

Publication types

Case Reports
Clinical Trial
Randomized Controlled Trial

MeSH terms

Aged
Double-Blind Method
Feasibility Studies
Female
Humans
Immunoglobulins
Pulmonary Disease, Chronic Obstructive* / diagnosis
Pulmonary Disease, Chronic Obstructive* / drug therapy
Treatment Outcome

Substances

Immunoglobulins

Associated data

ClinicalTrials.gov/NCT03018652
ClinicalTrials.gov/NCT02690038

Grants and funding

The study was supported in part by The Ottawa Hospital Academic Medical Organization Innovative Fund, CSL Behring, and Grifols. Funders were not involved in the study design, study conduct, result analysis or interpretation. DWC is supported in salary with a grant from the University of Ottawa and Department of Medicine.