Esmolol in Sepsis Management:Evaluating Immunomodulatory Effects and Impact on Patient Outcomes

Phase 2

Completed

• Conditions: Sympathetic Nervous System Diseases; Sepsis; Cytokine Storm; Immunologic Paralysis; Catecholamine; Overproduction; Beta-Blocker; Lymphocyte Disorder T
• Interventions: Drug: esmolol

• Registration Number: NCT06390748
• Lead Sponsor: Lin Chen

Brief Summary

Evaluate the effectiveness of esmolol, a selective β1-adrenergic receptor blocker, in modulating immune responses and improving patient outcomes in sepsis.

Detailed Description

The research aimed to investigate the immunomodulatory effects of Esmolol in sepsis treatment. A comprehensive study was conducted, incorporating both direct experimental assays and data extraction from Electronic Health Records (EHR) to evaluate physiological and immunological responses in septic patients. Specifically, Norepinephrine (NE) levels were measured, and CD4+/CD8+ T cells were quantified to assess changes influenced by Esmolol administration. Additionally, cytokine profiles, Procalcitonin (PCT) levels, complete blood counts (CBC), and routine biochemical functions were monitored through data retrieved from EHR systems, providing a broad perspective on patient health and response to treatment. This multifaceted approach aimed to determine how Esmolol affects key immune parameters and overall patient outcomes, addressing both the direct and systemic impacts of this treatment on septic patients.

Study Timeline

• Study Start: 2021-01-01
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Study First Submitted: 2024-04-21
• Study First Submitted QC: 2024-04-24
• Study First Posted: 2024-04-30
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-25
• Last Update Posted: 2024-05-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Patients aged between 18 and 90 years.
2. Diagnosed with sepsis or septic shock according to the diagnostic criteria in Suivival Sepsis of 2021.
3. Received adequate fluid resuscitation and necessary exogenous Norepinephrine (NE).
4. No contraindications to Esmolol and appropriate heart rate levels determined by clinical assessment.
5. Provided written informed consent.

Exclusion Criteria

1. Deceased within three days following ICU admission.
2. Pregnant or lactating individuals.
3. Underwent surgical procedures within the last two weeks.
4. Severe cardiac failure exceeding NYHA Class III.
5. Usage of long-term oral β-blockers or any form of extracorporeal circulation within the last two weeks.
6. Presenting with sinus bradycardia or atrioventricular block.
7. Received high doses of corticosteroids in the past three months.
8. Underwent significant hormone therapy, persistent blood loss of more than 500 ml within any 24-hour period, or were treated with Esmolol for less than three days.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
standard care plus esmolol	esmolol	Patients in this group were administered Esmolol, a beta-1 selective adrenergic blocker, alongside the standard sepsis care protocols. The dosage of Esmolol was adjusted to maintain heart rate within predefined targets. Additionally, daily electrocardiogram (ECG) monitoring was conducted to assess changes in the QT interval, a critical measure given the potential cardiac effects of beta-blockers. This group aimed to explore not only the immunomodulatory effects of Esmolol but also its safety profile in terms of cardiac function in septic patients.

Primary Outcome Measures

Name	Time	Method
Impact of Esmolol on Survival Rates	Survival rates will be monitored from the time of randomization until the end of the study period or until patient death, whichever comes first, up to 28 days post-randomization.	The primary outcome measure will be the comparison of survival rates between the treatment and control groups. A logistic regression analysis will be employed to evaluate the effect of Esmolol on survival rates and clinical outcomes, adjusting for potential confounders. Additionally, Kaplan-Meier survival curves will be generated for each group, and a Log-rank test will be used to compare the differences in survival rates over the study period.
Improvement in Organ Function and Inflammatory Markers	Organ function and inflammatory markers will be measured at baseline, then regularly throughout the patient's stay in the ICU, up to a maximum of 28 days.	As a secondary outcome, the study will assess the effect of Esmolol on organ function and systemic inflammation. This will be evaluated using a composite of changes in organ function scores (such as SOFA - Sequential Organ Failure Assessment score) and levels of inflammatory markers (such as C-reactive protein and IL-6). The analysis will determine if Esmolol correlates with an improvement in these clinical parameters, suggesting a protective or restorative effect on organ function.

Secondary Outcome Measures

Name	Time	Method
Length of Intensive Care Unit (ICU) Stay	From the date of ICU admission until the date of ICU discharge, assessed up to 90 days.	The duration of ICU stay will be measured to determine if Esmolol administration correlates with a shorter ICU admission period. This measure can reflect the overall impact of the drug on the severity and progression of sepsis, potentially indicating more rapid patient stabilization and recovery.
Reduction in Inflammatory Markers	Baseline and then daily measurements in ICU up to 28 days.	The study will evaluate the effect of Esmolol on systemic inflammation by measuring changes in inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) levels. A decrease in these markers could indicate a beneficial anti-inflammatory effect of the drug.

Trial Locations

Locations (1)

Sichuan Provincial People's Hospital; 🇨🇳 Chengdu, Sichuan, China