A single infusion of hyperimmune intravenous immunoglobulin (hIVIG) confers no clinical benefit for hospitalized patients with COVID-19 when administered with standard of care, including remdesivir, according to a study published in the Lancet.
Researchers from the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) performed an international, double-blind, placebo-controlled, phase 3 trial, Inpatient Treatment of COVID-19 With Anti-Coronavirus Immunoglobulin (ITAC) INSIGHT013 (ClinicalTrials.gov Identifier:NCT04546581), across 63 sites in 11 countries. For the study, investigators enrolled 593 adults hospitalized with COVID-19, who had no acute end-organ failure but who had been symptomatic for up to 12 days. Study participants were randomly assigned 1:1 to receive hIVIG in combination with standard of care, which included remdesivir, or to receive an equal volume of saline as placebo. Patients in the hIVIG group received a dose of 400 mg/kg bodyweight, limited to 40 g. The follow-up period was 28 days.
Researchers measured the primary outcome at day 7 by a 7-category ordinal endpoint that included pulmonary status and extrapulmonary complications and spanned from no limiting symptoms to death. Deaths and adverse events, including organ failure and severe infections, defined the composite safety outcomes at days 7 and 28.
The investigators performed prespecified subgroup analyses for efficacy and safety outcomes by duration of symptoms, the existence of anti-spike neutralizing antibodies, and other baseline factors. They conducted analyses on a modified intention-to-treat (mITT) population, which encompassed all randomly assigned individuals meeting the eligibility criteria and receiving all or part of the assigned study product infusion; 579 patients were included in the mITT analysis.
The hIVIG cohort vs placebo did not have significantly greater odds of a better outcome at day 7 (adjusted odds ratio (aOR), 1.06; 95% CI, 0.77-1.45; P=.72). Individuals in the hIVIG group vs placebo experienced infusion reactions, but overall infusions were well tolerated (18.6% vs 9.5%; P=.002). At day 7, the percentage with the composite safety outcome was similar for the hIVIG (24%) and placebo groups (25%; aOR, 0.98; 95% CI, 0.66-1.46; P =.91).
The study was limited by its sample size, which may not have permitted detection of a positive treatment effect smaller than that specified and had limited power to investigate clinical and immunological subgroups who might benefit from treatment with hIVIG. Another limitation was a lack of data on viral strains in participants.
“Although there was no evidence of clinical benefit in this hospitalized group when used with standard of care that includes remdesivir, a potential role for hIVIG might still be found in earlier disease stages of COVID-19 or special populations,” the study authors wrote.
Disclosure: Multiple authors declared affiliations with the pharmaceutical and biopharmaceutical industries. Please refer to the original article for a full list of disclosures.
Polizzotto MN, Nordwall J, Babiker AG, et al. Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial. Lancet. Published online January 27, 2022. doi:10.1016/S0140-6736(22)00101-5