Study: Individuals With COVID-Related ARDS Do Not Improve When Treated With IVIG

Individuals with COVID-19 who received ventilation for moderate-to-severe acute respiratory distress syndrome (ARDS) did not improve clinically when treated with intravenous immunoglobulins (IVIG), according to the results of a study posted in The Lancet Respiratory Medicine.

Additionally, investigators found that the IVIG treatment tended to be associated with an increased frequency, though not significant, of serious adverse events (AEs).

ARDS is a complication of COVID-19 and often is associated with high morbidity and mortality rates.

The primary outcome of the study was the number of ventilation-free days by day 28.

Between April 3, 2020, and October 20, 2020, 146 individuals were eligible for inclusion and were randomized into 2 groups. In the IVIG group, 69 individuals were included, while 77 were included in the placebo group. One individual in the IVIG group did not receive the treatment drug after being transferred to an emergency care unit for life support.

The intention-to-treat analysis showed no significant difference in the median number of ventilation-free days at 28 days between the 2 groups. Neither group met the primary outcome of ventilation free days by day 28. The mean number for both groups was 0.

However, serious AEs were reported in approximately 32% of those in the IVIG group compared with those in the placebo group, at 20%.

There were 3 AEs that led to unmasking in the placebo group.

There was no difference in the occurrence of ventilator-acquired pneumonia between both groups. However approximately 15% of individuals in the IVIG group had deep vein thrombosis compared with 4% of those in the placebo group.

Additionally, 4 of 10 individuals in the IVIG group had pulmonary embolism compared with 1 individual in the placebo group.

The sequential organ failure assessment and the lung injury scores at day 14 and day 28 were not statistically different between the 2 groups. However, lung compliance was significantly lower in the IVIG group at day 14.

The day 28- and 90-day follow-up of 7-category clinical ordinal scale between the IVIG and placebo groups were also similar, as well as the proportion of individuals discharged, at 37%, for both groups.

The median length of stays in hospitals and intensive care units was also similar for both groups.

The study, which was a double-blind, multicenter, placebo-controlled trial, was conducted at 43 centers in France. Individuals, receiving ventilation for up to 72 hours who had a polymerase chain reaction-confirmed COVID-19 infection, were given either an IVIG dosage of 2 g/kg over a 4-day period or a placebo.

All individuals were also associated with moderate-to-severe ARDS.

The assignments were randomized with a web-based system and stratified based on the center and duration of the ventilation before the trial. The stratifications included less than 12 hours, 12 to 24 hours, and more than 24 hours to 72 hours.

The treatment was also administered within the first 96 hours of ventilation. The mean time between symptom onset and initiation of ventilation was 8 days for both groups.

The severity of critical illness was similar between the 2 groups. The ventilation system did not differ between the 2 groups, nor did either group use corticosteroids and tocilizumab.

Additionally, investigators divided the IVIG admiration into 4 perfusions of 0.5 g/kg each to be administered over at least 8 hours to minimize the risk of any AEs. Individuals in the placebo arm received an equal volume of sodium chloride 0.9% over the same period.

The median follow-up time was 90 days.

Reference

Mazeraud A, Jamme M, Mancusi RL, et al. Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;10(2):158–66. doi:10.1016/S2213-2600(21)00440-9