Supplemental immunoglobulin (ivIgG) treatment in 163 patients with sepsis and septic shock — An observational study as a prerequisite for placebo-controlled clinical trials

Abstract

In a multicenter observational study of 163 medical and surgical patients with a total of 173 episodes of sepsis or septic shock (Elebute sepsis score: 19.0 +/- 0.5), the effects of supplemental i.v. immunoglobulin (i.v. IG) treatment (unmodified polyvalent IgG pH 4.25, n = 123; for Pseudomonas sepsis, n = 50, Pseudomonas IgG) on multiple organ failure (MOF) were investigated by means of APACHE II score changes (pretreatment: 23.7 +/- 0.6). In 44% of the cases ("responders"), a prompt improvement in APACHE II score (defined as decrease greater than or equal to 4) was evident from day 0 to day 4 after onset of therapy, thus being in close time relationship to the i.v. IG administration. This improvement, associated with a better prognosis (mortality 24% vs. 55%), was found in all subgroups, most importantly the following: polyvalent IgG vs. Pseudomonas IgG treatment; medical vs. surgical patients; moderate vs. severe MOF; and gram-positive vs. gram-negative septicemia. In a small-sized second comparative nonrandomized control group (n = 27, antibiotic treatment alone) of septic patients (Elebute: 14.7 +/- 1.0) with similar MOF severity (APACHE II: 23.6 +/- 1.4), the response rate (30%) was, though not statistically significant, lower by one-third. The optimal baseline score ranges for patient inclusion into future placebo-controlled randomized i.v. IG trials were found to be 20-35 for the APACHE II score and 12-27 for the Elebute score.

Open randomized phase II trial of an extracorporeal endotoxin adsorber in suspected Gram-negative sepsis*

“…Indeed, Rivers et al (30) found a slight but significant difference in serial APACHE II scores (3 points) to be associated with a 16% difference in mortality when comparing early goal-directed therapy with standard therapy in patients with sepsis. The specific 4-point reduction used in our study has also been shown to predict improvements in 28-day mortality rate in previous sepsis studies (23,24). The SOFA score was also calculated, since changes in this score also relate to mortality rate and SOFA provides discrimination between specific organ systems.…”

“…We have therefore performed an initial multiple-center phase II study of the safety and therapeutic effect of this adsorption treatment in presumed Gram-negative sepsis. A reduction in the Acute Physiology And Chronic Health Evaluation (APACHE) II score of Ն4 points over the first 4 days was chosen as primary end point, since this has been shown to predict improved 28-day mortality rate in studies of immunoglobulin therapy in septic patients (23,24).…”

Supplemental immune globulins in sepsis: a critical appraisal

“…In an observational study, where 163 septic patients were treated with lgG-IVIG, likewise no increase in serum creatinine was observed within the first four days after receiving PolyglobinR Nand PsomaglobinR N (Bayer AG, Leverkusen, Germany) on day 0 and day I, repectively. Serum creatinine (mean values) on day 0 were 2·4-2·5mg/100ml and on day 4, 2·2-2·3mg/IOOml [24]. For viral safety of IVIG, see Yap, this supplement, pp 35-42.…”

“…The protocol of the SBITS study has been published [14), and the results will be available by the end of 1996. The estimations of the expected mortality in the placebo group and the reduction of mortality in the treatment group rely on the data from a preceding observational study [24) and reflect the selection of patient subgroups included. in contrast to the qualitative sepsis criteria usually applied, the SBITS study, for the first time, uses quantitative score inclusion criteria regarding assessment of sepsis and disease severity, the sector with potentially maximal benefit as previously validated [24).…”

“…The estimations of the expected mortality in the placebo group and the reduction of mortality in the treatment group rely on the data from a preceding observational study [24) and reflect the selection of patient subgroups included. in contrast to the qualitative sepsis criteria usually applied, the SBITS study, for the first time, uses quantitative score inclusion criteria regarding assessment of sepsis and disease severity, the sector with potentially maximal benefit as previously validated [24). The combined 'score inclusion window' of an Elebute sepsis score between 12 and 27 and an APACHE II score between 20 and 35 best warrants proof of the efficacy of the drug put to test, because patients with a low mortality per se and good prognosis are excluded because a very large number of them would be necessary to document additional test drug efficacy.…”