A Randomized Double-blind Placebo-controlled Feasibility Study of IVIG Therapy in Lung Transplantation.

Background: IVIG therapy may be clinically beneficial following lung transplantation (LTx), either by correcting hypogammaglobulinemia or by mitigating the humoral response to the lung allograft. However, the evidence base in LTx is limited. We aimed to recruit 40 LTx patients into a pilot placebo-controlled study of adding IVIG therapy to standard immunosuppression. The primary aim of the study was to provide feasibility data to inform the subsequent design of a definitive phase 2/3 randomized controlled trial. Methods: Stable patients were recruited between 3 and 6 mo post-LTx to receive 6 monthly infusions of either IVIG (0.4 g/kg) or placebo. Patients were followed for 12 mo. Primary study outcomes were related to feasibility; namely, the proportion of patients who (1) were screened to be eligible, (2) were eligible and enrolled, (3) lost to follow-up, and (4) received their allocated treatment. Although clinical data were collected, the study was not designed or powered to detect significant differences in clinical or adverse events. Results: Recruitment into the study was significantly impacted by the COVID pandemic. The final study cohort either received IVIG (n = 18) or placebo (n = 19). Four patients on IVIG did not receive the full complement of 6 study infusions because of infusion reactions. Otherwise, there was no significant difference in the safety profile between the 2 study arms. Four patients, all randomized to placebo, were unblinded because of clinical concerns and started on open-label IVIG. Serum IgG levels increased, and the incidence of hypogammaglobulinemia was lower in the IVIG-treated arm. Conclusions: The use of IVIG was relatively well tolerated in LTx recipients. The extracted clinical and safety data support consideration and the design of a definitive multicenter randomized controlled trial of IVIG in LTx. Clinical Trial Registration: Australian and New Zealand Clinical Trial Registry: ACTRN12618001394235.