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

Sepsis Clinical Trial

Official title:

Investigating the Immunomodulatory Effects of Esmolol in Sepsis Management and Its Impact on Patient Outcomes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06390748
• Other study ID #: SichuanPPHLC02
• Status: Completed
• Phase: Phase 2
• Start date: January 1, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: May 2024
• Source: Sichuan Provincial People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Autonomic Nervous System Diseases
• Beta-Blocker
• Catecholamine; Overproduction
• Cytokine Release Syndrome
• Cytokine Storm
• Immunologic Paralysis
• Nervous System Diseases
• Paralysis
• Sepsis
• Sympathetic Nervous System Diseases
• Toxemia

Intervention

Drug:
• esmolol
The primary intervention is the administration of Esmolol. Esmolol was specifically used to evaluate its immunomodulatory effects in patients with sepsis in the study. The dosage was tailored to achieve optimal heart rate control, an integral part of the therapeutic strategy aiming to mitigate the hyperadrenergic state often seen in sepsis. Alongside Esmolol, daily electrocardiogram (ECG) monitoring was incorporated to observe any changes in the QT interval, ensuring cardiac safety due to the known potential cardiac effects of beta-blockers.

Locations

Country	Name	City	State
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Lin Chen

Country where clinical trial is conducted

China, 

References & Publications (1)

Pedicino D, Volpe M. beta1-Adrenergic receptor stimulation modulates immune response in cancer: a role for beta-blockers in antineoplastic treatment? Eur Heart J. 2024 Mar 14;45(11):870-871. doi: 10.1093/eurheartj/ehae008. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact of Esmolol on Survival Rates	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.	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.
Primary	Improvement in Organ Function and Inflammatory Markers	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.	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.
Secondary	Length of Intensive Care Unit (ICU) Stay	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.	From the date of ICU admission until the date of ICU discharge, assessed up to 90 days.
Secondary	Reduction in Inflammatory Markers	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.	Baseline and then daily measurements in ICU up to 28 days.