The trial was registered at the dutch trial register, accessible at the ICTRP search portal (trialsearch

The trial was registered at the dutch trial register, accessible at the ICTRP search portal (trialsearch.who.int no. coronavirus disease 2019 (COVID-19) with increased mortality rates and may suffer reduced protection from vaccination [1C4]. An unprecedented number of randomized trials exhibited that plasma-derived antibody treatment, such as convalescent plasma or hyperimmune globulin, does not improve outcome in hospitalized COVID-19 patients. However, severely immunocompromised patients are grossly underrepresented in these trials [5C11]. We hypothesized that severely immunocompromised patients with COVID-19 are likely to benefit most from such interventions, and we set out to examine the effects of antisevere acute respiratory syndrome coronavirus 2 hyperimmune intravenous globulin (COVIG) in this population in a double-blind, controlled, randomized fashion. METHODS The study included adult patients who were severely immunocompromised (as defined in the Study Protocol, which is included as a Data Supplement available with the online version of this article) and who were hospitalized with a polymerase chain reaction-confirmed, symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contamination within 72 hours after admission. Patients that had received prior treatment with convalescent plasma or intravenous immunoglobulin (IVIG) with neutralizing SARS-CoV-2 antibodies, patients with hypersensitivity to IVIG, or patients that required respiratory support with endotracheal intubation or high-flow nasal oxygen were excluded. Patients were randomly assigned in a 1:1 ratio to receive 150 mL:100 mg/mL COVIG or 150 mL:100 mg/mL of IVIG (control). Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin was derived from a single batch, made up of a neutralizing titer of 900 IU/mL (VNT50) against wild-type SARS-CoV-2 [12]. The aim of this dose was to achieve equipotency to convalescent plasma treatment as was used in large, randomized studies [5C10]. Intravenous immunoglobulin was derived from a single batch generated before December 2019 and, thus, did not contain SARS-CoV-2 antibodies. Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin and IVIG production were comparable, except that for COVIG production, convalescent plasma was derived from donors who Mouse monoclonal to MUSK had a history of symptomatic COVID-19 and had recovered from COVID-19 for at least 14 days before plasma donation. All convalescent plasma models were tested by a quantitative immunoglobulin G (IgG) enzyme-linked immunosorbent assay test that correlated with computer virus neutralizing antibodies. Both COVIG and IVIG were produced by Prothya (the Netherlands) and labeled similarly as Nanogam. Randomization was performed by computer, stratified according to the origin of the immunocompromised state. All investigators, research staff, and participants were blinded to the allocated treatment until day 28, but unblinding was possible before day 28 when the primary endpoint was reached. Baseline data were collected using a web-based case report form. At baseline and after treatment, serum SARS-CoV-2 antibody measurements were performed using LIAISON SARS-CoV-2 TrimericS IgG assay (DiaSorin). Positivity was defined as anti-S IgG > 33.8 BAU/mL. The primary endpoint of this Btk inhibitor 1 R enantiomer hydrochloride study was the occurrence of severe COVID-19, evaluated up until day 28 after treatment, and defined as any of the following conditions: (1) respiratory deterioration requiring high-flow nasal oxygen or mechanical ventilation; (2) intensive care unit (ICU) admission for respiratory deterioration; (3) lack of clinical improvement from day 7 (no improvement in oxygen requirement or, in patients not requiring oxygen, Btk inhibitor 1 R enantiomer hydrochloride in disease burden and fever); or (4) readmission for COVID-19. Secondary endpoints included occurrence of severe COVID-19 in the subgroup of patients Btk inhibitor 1 R enantiomer hydrochloride that had no SARS-CoV-2 antibodies upon inclusion, duration of hospitalization, 28-day mortality, the 4 individual endpoints Btk inhibitor 1 R enantiomer hydrochloride that compose the primary endpoint, and serious adverse events. We estimated that this high-risk patient group had a 70% chance of reaching the primary endpoint of severe COVID-19, and we hypothesized a reduction to 30% with COVIG treatment. With a power of 90%, a 2-sided alpha of 5%, and a single preplanned efficacy interim analysis, a sample size of 86 participants was required. However, the trial was terminated prematurely when, based on the results of the RECOVERY trial, monoclonal antibodies casirivimab/imdevimab became recommended for seronegative, hospitalized COVID-19 patients by the Dutch COVID-19 treatment guideline, because it was ethically inacceptable to withhold casirivimab/imdevimab therapy for patients in the trial [13]. Intention-to-treat analysis.