High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial.

Critical care Esomeprazole Intensive care unit Mortality Proton pump inhibitors SOFA score Sepsis Septic shock

Journal

Contemporary clinical trials

ISSN: 1559-2030

Titre abrégé: Contemp Clin Trials

Pays: United States

ID NLM: 101242342

Informations de publication

Date de publication:
Oct 2023

Historique:

received: 31 03 2023

revised: 12 08 2023

accepted: 22 08 2023

pubmed: 26 8 2023

medline: 26 8 2023

entrez: 25 8 2023

Statut: ppublish

Résumé

Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock. This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality. This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock. This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality.

DISCUSSION CONCLUSIONS

This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock.

TRIAL REGISTRATION BACKGROUND

This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.

Identifiants

DOI: 10.1016/j.cct.2023.107319 PMID: 37625587

pubmed: 37625587

pii: S1551-7144(23)00242-2

doi: 10.1016/j.cct.2023.107319

pii:

doi:

Banques de données

ClinicalTrials.gov

['NCT03452865']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

107319

Investigateurs

Lorenzo Cianfanelli (L)

Sergio Colombo (S)

Elena Moizo (E)

Milena Mucci (M)

Massimiliano Nuzzi (M)

Davide Oreggia (D)

Alessandro Oriani (A)

Gloria Panozzo (G)

Nicola Pasculli (N)

Valentina Plumari (V)

Davide Salaris (D)

Stella Sordoni (S)

Stefano Turi (S)

Anna Rubartelli (A)

Roberto Sitia (R)

Angela Corea (A)

Giuseppe Neri (G)

Rubia Baldassarri (R)

Michela Villano (M)

Erika Taddei (E)

Alessandro Isirdi (A)

Francesco Meroi (F)

Daniele Orso (D)

Fabio Toffoletto (F)

Enrico De Cesaris (E)

Carlo Leggieri (C)

Paolo Mario Enrico Seraglio (PME)

Valery Likhvantsev (V)

Alessia Mattei (A)

Lorenzo Schiavoni (L)

Carmine Domenico Votta (CD)

Massimiliano Greco (M)

Aigerim Yeltayeva (A)

Massimo Baiocchi (M)

Giuseppe Bono (G)

Sabrina Boraso (S)

Luca Cabrini (L)

Matteo Cairo (M)

Andrea Cortegiani (A)

Gennaro De Pascale (G)

Laura Pasin (L)

Fulvio Pinelli (F)

Vincenzo Pota (V)

Salvatore Sardo (S)

Massimo Sergi (M)

Barbara Usai (B)

Antonio De Sio (A)

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.