Study of Early Enteral Dextrose in Sepsis

Not Applicable

Completed

• Conditions: Sepsis
• Interventions: Other: Enteral Dextrose Infusion; Other: Free Water Infusion

• Registration Number: NCT03454087
• Lead Sponsor: University of Pittsburgh

Brief Summary

This study is a prospective single-center randomized double-blinded placebo-controlled clinical trial testing the effects of early enteral dextrose as a therapeutic agent in critically ill patients with sepsis. Primary outcomes are differences in circulating plasma levels of the pro-inflammatory cytokine IL-6 to be tested 24 hours after the start of enteral infusion. Secondary outcomes include differences in circulating incretin hormone levels, differences in other pro-inflammatory cytokines including IL-1β and TNF-α, changes in intestinal microbial composition and function after intervention, glycemic control and variability as assessed by capillary blood glucose measurements and exogenous insulin dosing during the intervention period, and clinical outcomes including intensive care unit (ICU) and hospital stay and in-hospital mortality.

Detailed Description

The central objective of this research project is to determine how early caloric support impacts inflammatory and metabolic outcomes in the acute phase of sepsis. Preliminary data from our mouse models suggest that provision of dextrose via an intravenous route, even at low levels early in the course of sepsis, markedly impairs glucose tolerance and decreases insulin sensitivity and insulin secretion. In contrast, provision of low-level dextrose by the enteral route at identical levels during the early phase of sepsis is associated with decreased inflammation, increased secretion of beneficial intestine-derived incretin hormones, and significant improvements in glucose metabolism. The goals of this clinical study are to translate findings on the beneficial role of early enteral dextrose in a pilot interventional trial in critically-ill patients with sepsis. This clinical trial will provide further insight into the optimal timing and route of early caloric support in the care of septic patients-an area of clinical practice that will benefit from further studies in fundamental biology and clear guidelines for physicians.

Study Timeline

• Study First Submitted: 2018-02-19
• Study First Submitted QC: 2018-02-26
• Study First Posted: 2018-03-05
• Study Start: 2018-06-04
• Primary Completion: 2020-03-02
• Status Verified: 2020-04
• Study Completion: 2020-04-01
• Last Update Submitted: 2020-04-03
• Last Update Posted: 2020-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

1. New presentation of sepsis characterized by a confirmed or suspected infection, with an acute increase from baseline in a modified Sepsis-Related Organ Failure Assessment (SOFA) score of greater than or equal to 2 points. If baseline values are unknown, baseline SOFA score of 0 will be assumed.
2. Available enteral access defined by: (1) an existing nasogastric or orogastric tube, (2) plans to place a nasogastric or orogastric tube, or (3) an existing percutaneous endoscopic gastrostomy (PEG) tube.
3. Less than 48 hours since meeting criteria for sepsis.
4. Expected to stay at least 24 hours in the ICU.

Exclusion Criteria

1. Pre-existing continuous enteral tube feed use prior to study entry.
2. Diabetic ketoacidosis or diabetic hyperosmolar hyperglycemic syndrome.
3. Previously enrolled in this study within the same hospital admission.
4. ICU physician request to exclude patient based on clinical assessment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Enteral Dextrose Infusion	Enteral Dextrose Infusion	Critically-ill participants with sepsis enrolled in the interventional arm will receive a 24-hour infusion of dextrose solution by the enteral route to be initiated via an existing nasogastric or orogastric tube within the first 48 hours of meeting sepsis criteria.
Placebo	Free Water Infusion	Critically-ill participants with sepsis in the placebo arm will receive a 24-hour enteral free water infusion via an existing orogastric or nasogastric tube within 48 hours of meeting sepsis criteria.

Primary Outcome Measures

Name	Time	Method
Plasma IL-6	24 hours after start of infusion	Pro-inflammatory cytokine

Secondary Outcome Measures

Name	Time	Method
Mortality	30 days	In-hospital mortality at 30 days
Additional pro-inflammatory cytokines	24 hours after start of infusion	Circulating levels of other pro-inflammatory cytokines including IL-1 beta and TNF-alpha (each to be determined in pg/mL)
Incretin hormone levels	24 hours after start of infusion	Circulating levels of the intestine-derived hormones GIP and GLP-1 (each to be determined in pg/mL)
Microbiome composition	24 hours after start of infusion	Analysis of the composition and distribution of microorganisms of the gut and respiratory microbiome measured after intervention from tracheal aspirates and rectal swabs
Glycemic control	First 24 hours	Capillary blood glucose measurements during infusion period

Trial Locations

Locations (1)

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States