Settings: multinational, randomized, double- blind, placebo-controlled clinical trial conducted in 17 centers in Italy, Russia, and Kazakhstan

Participants: A total of 307 ICU patients with sepsis or septic shock. Patients who were likely to die (APACHE II > 65 points) were excluded.

Treatment group: 80 mg bolus of omeprazole at randomization, at 12 hours and infusion of 12 mg/hour for 72 hours. Total dose of 1024 mg.

Outcome measurement: primary outcome of the study was organ dysfunction measured as the mean daily SOFA score during the first 10 days. Secondary outcomes were antibiotics-free days at 28 days; all-cause mortality at 28 days

Study Results:

• At 10 days, there was no difference in the median mean daily SOFA score: 5 (IQR, 3–10) in the mega- dose esomeprazole and 5 (IQR, 3–9) in the placebo groups (risk difference [RD], 0.1; 95% CI, –0.8 to 1.0; p > 0.99).
• At day 28, the median antibiotic-free days were 15 (IQR, 0–21) in the mega-dose esomeprazole group vs. 13 (IQR, 0–21) in the placebo group (p = 0.62).
• All-cause mortality at 28 days was 25% in the mega- dose esomeprazole group and 20% in the placebo group (RD, 4.9; 95% CI, –4.5 to 14.2; p = 0.31).

Discussion:

• The authors also did in vitro assays and they detected reduced levels of anti-inflammatory cytokines among patients receiving megadose of omeprazole. However, these in vitro results did not translate into clinical benefits in these patients with sepsis.
• Apparently, this study is another example that animal studies may not translate into clinical benefits in human studies, especially sepsis , as this condition is highly heterogeneous.

Conclusion: 

In sepsis patients, Esomeprazole did not re- duce organ dysfunction, despite demonstrating in vivo immunomodulatory effects

References

Monti G, Carta S, Kotani Y, Bruni A, Konkayeva M, Guarracino F, Yakovlev A, Cucciolini G, Shemetova M, Scapol S, Momesso E, Garofalo E, Brizzi G, Baldassarri R, Ajello S, Isirdi A, Meroi F, Baiardo Redaelli M, Boffa N, Votta CD, Borghi G, Montrucchio G, Rauch S, D'Amico F, Pace MC, Paternoster G, Vitale F, Giardina G, Labanca R, Lembo R, Marmiere M, Marzaroli M, Nakhnoukh C, Plumari V, Scandroglio AM, Scquizzato T, Sordoni S, Valsecchi D, Agrò FE, Finco G, Bove T, Corradi F, Likhvantsev V, Longhini F, Konkayev A, Landoni G, Bellomo R, Zangrillo A; PPI-SEPSIS Study Group. A Multinational Randomized Trial of Mega-Dose Esomeprazole as Anti-Inflammatory Agent in Sepsis. Crit Care Med. 2025 Aug 1;53(8):e1554-e1566. doi: 10.1097/CCM.0000000000006720. Epub 2025 May 29. PMID: 40439536.