Esmolol to Treat the Hemodynamic Effects of Septic Shock

NCT02369900 | Terminated Phase 2 Results DMC

• 2 other identifiers: 2014P00041515SDG22420010
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to determine the effects of controlling the heart rate of patients with septic shock using an intravenous medication called esmolol.

Conditions

Septic Shock; Hypotension; Tachycardia

Keywords

Esmolol; Septic Shock; Hypotension; Tachycardia

Outcome Measures

Primary Outcomes (1)

• Need for Vasopressor Support, Measured as Mean Norepinephrine Equivalent Dose (mcg/kg/Min), at 6hr Time Point

  The primary endpoint will be mean norepinephrine equivalent dose (mcg/kg/min) at 6 hours after onset of study drug. For the vasopressor vasopressin, the dose of vasopressin was multiplied by 2.5 in order to create a norepinephrine equivalent dose. For the vasopressor phenylephrine, the dose of phenylephrine was divided by 10 in order to create a norepinephrine equivalent dose.

  6 hours

Secondary Outcomes (10)

• Overall Need for Vasopressor Support

  12 and 24 hours

• Heart Rates Between Groups

  6 and 12 hours

• Time to Shock Reversal

  Duration of hospitalization, limit 180 days

• Lactate

  6, 12, and 24 hours

• Oxygen Consumption (VO2)

  12 and 24 hours

Study Arms (2)

Esmolol infusion

ACTIVE COMPARATOR

Esmolol infusion for 24 hours. Esmolol will be titrated to a heart rate of 80 - 94 per minute, starting at 10mcg/kg/min and subsequently increasing every 20 minutes in increments of 10 mcg/kg/min (or slower at the discretion of the team) until target is achieved. The maximum allowed dose will be 300mcg/kg/min. Patients, irrespective of treatment group, will be managed at the discretion of the clinical team. BIDMC has internal guidelines for the management of septic shock which reflect the most recent 2012 Surviving Sepsis Campaign guidelines and are incorporated into the care of patients with septic shock in the ICUs

Drug: Esmolol

Standard care, Saline

PLACEBO COMPARATOR

Standard care (no esmolol). Patients, irrespective of treatment group, will be managed at the discretion of the clinical team. BIDMC has internal guidelines for the management of septic shock which reflect the most recent 2012 Surviving Sepsis Campaign guidelines and are incorporated into the care of patients with septic shock in the ICUs

Other: Saline

Interventions

Esmolol DRUG

Also known as: Beta Blocker

Esmolol infusion

Saline OTHER

Also known as: Normal Saline

Standard care, Saline

Eligibility Criteria

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

You may qualify if:

• Adult (≥ 18 years)
• Sepsis defined as suspected or confirmed infection with at least two systemic inflammatory response syndrome (SIRS) criteria
• Norepinephrine (minimum 0.1 mcg/kg/min) support to maintain a mean arterial pressure ≥ 65 mmHg despite appropriate volume resuscitation (as defined by the clinical team, however at least 30mL/kg intravenous fluid
• Heart rate ≥ 95 per minute for at least 2 hours prior to enrollment
• hours since ICU admission

You may not qualify if:

• Intravenous β-blocker therapy prior to randomization
• Pronounced cardiac dysfunction (i.e. cardiac index \[CI\] ≤ 2.2 L/min/m2)
• Known significant valvular heart disease
• Research-protected populations (pregnant women, prisoners, intellectually disabled)
• Known "Do-not-resuscitate" or "do-not-intubate" order at the time of enrollment
• Infusion of epinephrine, dopamine, dobutamine or milrinone at time of enrollment
• Known allergy/sensitivity to esmolol or history of asthma/COPD

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• American Heart Association: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Cocchi MN, Dargin J, Chase M, Patel PV, Grossestreuer A, Balaji L, Liu X, Moskowitz A, Berg K, Donnino MW. Esmolol to Treat the Hemodynamic Effects of Septic Shock: A Randomized Controlled Trial. Shock. 2022 Apr 1;57(4):508-517. doi: 10.1097/SHK.0000000000001905.

  PMID: 35066509 DERIVED

MeSH Terms

Conditions

Shock, Septic; Hypotension; Tachycardia

Interventions

esmolol; Adrenergic beta-Antagonists; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Cardiac Conduction System Disease

Intervention Hierarchy (Ancestors)

Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

The trial ended early due to slow enrollments and ending of funding before the target enrollment was reached. Many patients with septic shock were excluded because of the absence of tachycardia, or due to the presence of myocardial dysfunction. We did not collect echocardiographic data. Patients in the esmolol arm had differing exposures to esmolol, based on variable dosing and duration due to individual patient characteristics.

Results Point of Contact

• Title: Michael N. Cocchi MD
• Organization: Beth Israel Deaconess Medical Center

mcocchi@bidmc.harvard.edu

617-754-2388

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Michael N Cocchi MD

Study Record Dates

• First Submitted: February 18, 2015
• First Posted: February 24, 2015
• Study Start: March 1, 2015
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: June 28, 2021
• Results First Posted: June 28, 2021

Record last verified: 2021-06

Locations

US (1)