POCUS-Guided Esmolol in Septic Shock: A Pilot RCT

NCT07313605 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 127880
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this pilot clinical trial is to determine if conducting a larger study using point-of-care ultrasound (POCUS) to guide beta-blocker therapy in patients with septic shock is feasible. Septic shock is a life-threatening condition where infection causes dangerously low blood pressure, requiring medications to support the heart and circulation. In septic shock, the body's stress response causes the heart to beat too fast, which can worsen organ damage. Beta-blockers are medications that slow the heart rate and may improve outcomes, but previous studies have shown mixed results. Some patients may be harmed by beta-blockers if they have not received enough fluids or if their heart is not functioning well. This study uses ultrasound to identify patients who are most likely to benefit and least likely to be harmed by beta-blocker therapy. The main questions this study aims to answer are: Is it feasible to recruit patients, obtain consent, perform ultrasound screening, and follow the study protocol? Researchers will compare two groups: one receiving the beta-blocker esmolol versus another receiving standard care, to assess the feasibility of a larger trial. Participants in the esmolol group will receive an intravenous infusion titrated to achieve a target heart rate of 75-95 beats per minute for up to 5 days or until shock resolves. All participants will be monitored for 90 days to track survival and organ function.

Conditions

Septic Shock

Outcome Measures

Primary Outcomes (4)

• Recruitment Rate

  Number of participants enrolled during the recruitment period who successfully complete study procedures and follow-up.

  From study initiation to end of recruitment, approximately 25 months

• Consent Rate

  The total number of eligible participants consented divided by the total number of eligible participants approached for consent

  From study initiation to end of recruitment, approximately 25 months

• POCUS Screening Completion Rate

  Number of participants who successfully underwent fluid responsiveness and cardiac function evaluation using point-of-care ultrasound, divided by the total number of participants eligible for POCUS screening. A successful POCUS entails acquiring adequate quality images for interpretation and providing conclusive assessments of fluid responsiveness, left ventricular function, and right ventricular function.

  From study initiation to end of recruitment, approximately 25 months

• Protocol Adherence

  Intervention arm: The number of participants who received esmolol as per protocol divided by the total number of participants randomized to the intervention arm, and the total time spent within heart rate target divided by total time on esmolol infusion. Control arm: The number of participants who did not receive any beta-blocker therapy during the 5-day study period divided by the total number randomized to the control arm.

  From day of randomization (day 1) to day 5

Secondary Outcomes (5)

• 28-Day Mortality

  From randomization to 28 days

• 90-Day Mortality

  From randomization to 90 days

• Duration of Mechanical Ventilation

  From randomization to 28 days

• Duration of Vasoactive Medications

  From randomization to 28 days

• Provision of Renal Replacement Therapy

  From randomization to 28 days

Other Outcomes (9)

• Heart Rate Separation

  From randomization to day 5

• Mean Arterial Pressure

  From randomization to day 5

• Vasopressor Requirements

  From randomization to day 5

Study Arms (2)

Standard Care

NO INTERVENTION

Patients randomized to this arm will receive standard care for septic shock according to Surviving Sepsis Campaign guidelines. This includes fluid resuscitation, a mean arterial pressure target of 65 mmHg or greater, early broad-spectrum antibiotics, source control when applicable, vasopressor support with norepinephrine as the first-line agent, stress-dose corticosteroids, early nutrition, and lung-protective mechanical ventilation when required. Beta-blockers and calcium channel blockers are prohibited throughout the 5-day study period. For patients who develop new-onset atrial fibrillation or flutter, amiodarone will be the preferred first-line antiarrhythmic agent. Treating physicians may use other antiarrhythmic medications at their discretion, provided they are not beta-blockers or calcium channel blockers.

Esmolol

EXPERIMENTAL

Patients will receive an intravenous infusion of esmolol, an ultra-short-acting cardioselective beta-1 adrenergic receptor antagonist with a half-life of approximately 9 minutes. The infusion will be titrated to achieve a target heart rate of 75-95 beats per minute, with a maximum dose of 300 mcg/kg/minute. Treatment will continue for a maximum of 5 days or until ICU discharge, death, or resolution of shock (defined as discontinuation of vasopressors for at least 6 hours). Esmolol will be the preferred first-line treatment for tachyarrhythmias. All patients will continue to receive standard care for septic shock per Surviving Sepsis Campaign guidelines.

Drug: Esmolol

Interventions

Esmolol DRUG

Patients will receive an intravenous infusion of esmolol, an ultra-short-acting cardioselective beta-1 adrenergic receptor antagonist with a half-life of approximately 9 minutes. The infusion will be titrated to achieve a target heart rate of 75-95 beats per minute, with a maximum dose of 300 mcg/kg/minute. Treatment will continue for a maximum of 5 days or until ICU discharge, death, or resolution of shock (defined as discontinuation of vasopressors for at least 6 hours). Esmolol will be the preferred first-line treatment for tachyarrhythmias. All patients will continue to receive standard care for septic shock per Surviving Sepsis Campaign guidelines.

Esmolol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Within 24 hours of diagnosis of septic shock based on Sepsis-3 criteria (requirement for vasopressors to maintain organ perfusion, lactate greater than 2 mmol/L, suspected or confirmed infection)
• Within 72 hours of ICU admission
• Tachycardia with heart rate 100 beats per minute or greater, defined as either sinus tachycardia or atrial fibrillation/flutter

You may not qualify if:

• Known allergy to beta-blockers
• Second or third-degree heart block without a functioning pacemaker
• Acute bronchospasm or status asthmaticus
• Pregnancy
• Patient receiving extracorporeal membrane oxygenation
• Decision to limit life-sustaining therapies
• Untreated pheochromocytoma
• Fluid-responsive patients as determined by POCUS assessment
• Moderate to severe right ventricular and/or systolic left ventricular dysfunction as determined by POCUS assessment
• Patient already receiving calcium channel blocker or beta-blocker therapy

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: collaborator
• John Basmaji: lead
• Western University, Canada: collaborator

Related Publications (1)

• McChesney C, Orozco N, Fiorini K, Wong MYS, Slessarev M, Prager R, Kao R, Leligdowicz A, Sharif S, Lewis K, Rochwerg B, Honarmand K, Ball IM, Arntfield R, Houlton R, VanNynatten L, Basmaji J. Impact of Short-Acting Beta-Blockers on the Outcomes of Patients With Septic Shock: A Systematic Review and Meta-Analysis. Crit Care Med. 2025 May 1;53(5):e1125-e1139. doi: 10.1097/CCM.0000000000006604. Epub 2025 Feb 26.

  PMID: 40009025 RESULT

MeSH Terms

Conditions

Shock, Septic

Interventions

esmolol

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• John Basmaji

  Western University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Basmaji Basmaji, MD

CONTACT

1-519-685-8500 Ext. 55661; john.basmaji@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: "Assistant Professor, Division of Critical Care Medicine, Department of Medicine, Western University

Study Record Dates

• First Submitted: December 17, 2025
• First Posted: January 2, 2026
• Study Start: January 15, 2026
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): April 15, 2028
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share