Esmolol to Control Adrenergic Storm in Septic Shock- ROLL-IN 2

NCT03208257 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: 1050522
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Septic shock is a common syndrome caused by the body's response to an infection. Septic shock is responsible for 10% of all ICU admissions and 30% of ICU deaths. Use of "beta blocker" medications may improve outcomes after septic shock. This pilot study evaluates protocols to infuse the beta blocker esmolol in patients with septic shock.

Conditions

Septic Shock

Keywords

esmolol; adrenergic storm; septic shock

Outcome Measures

Primary Outcomes (1)

• Organ-failure-free days

  28 days

Secondary Outcomes (5)

• All-cause hospital mortality

  During hospitalization

• All-cause 28-day and 90-day mortality

  28 days and 90 days

• Peak serum high-sensitivity troponin

  24 hours

• Left ventricular (LV) longitudinal strain

  24 hours

• ICU-free days

  28 days

Study Arms (1)

Esmolol

EXPERIMENTAL

Intravenous esmolol will be administered as a continuous infusion according to protocol to control tachycardia with maximal infusion rates in the range of 10-40 mcg/kg/min.

Drug: Esmolol

Interventions

Esmolol DRUG

Esmolol hydrochloride infusion

Also known as: BREVIBLOC

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
• Within 72 hours of admission to the ICU and septic shock (sepsis present at time of admission)
• a. Septic shock defined by SEPSIS-3 consensus criteria as i. Suspected or documented infection ii. Sequential Organ Failure Assessment (SOFA) score increased by at least 2 points over baseline iii. Lactate \> 2mmol/L iv. Receiving vasopressors to treat hypotension after at least 20 ml/kg intravenous crystalloid volume expansion
• Receiving vasopressors through a central venous catheter for more than 60 minutes.
• Arterial catheter in place or expected to be placed imminently.
• Heart rate \> 90/min while receiving vasopressors for more than 60 minutes.
• Adequately volume expanded, as manifest by any of the following, performed as part of routine clinical care (i.e., no study procedures will be performed before signed consent). If none of these measures are clinically available, the clinical attending must confirm that volume expansion is adequate. (After enrollment, a final safety check will confirm the adequacy of volume expansion.)
• Central venous pressure (CVP) \> 15 mm Hg.
• Negative Passive-Leg Raise (PLR) maneuver (\<10% increase in cardiac output after PLR).
• No cardiac output response (\<10% increase) after rapid infusion (\<5 min) of 250 ml of IV crystalloid (i.e., a graded volume expansion challenge \[GVEC\]).
• Inferior vena cava (IVC) plethora
• For patients who happen to be breathing passively (i.e., paralyzed or deeply sedated) on a positive pressure mechanical ventilator delivering at least 8 ml/kg tidal volumes and in normal sinus rhythm, stroke volume variability \<13% (such patients are acknowledged to be uncommon; the protocol does not recommend or require the induction of passive breathing).

You may not qualify if:

• Lack of informed consent.
• Currently receiving ExtraCorporeal Membrane Oxygenation (ECMO).
• Known pregnancy or nursing.
• Patient is a prisoner.
• Patient on hospice (or equivalent comfort care approach) at or before the time of enrollment.
• Known or current atrial fibrillation.
• Previously enrolled in the trial.
• Known allergy to esmolol or vehicle (see Appendix 2 for BREVIBLOC vehicle ingredients).
• Receipt of nodal blocking agents (see Appendix 3 for list of such agents) within three half lives
• Hemoglobin \< 7 gm/dl.
• Cardiac arrest within 24 hours.
• Pulmonary hypertension (moderate or severe), from documented history of prior right heart catheterization or current evidence on transthoracic echocardiogram (TTE) of any of the following
• Mean Pulmonary Arterial Pressure (mPAP) ≥ 35mmHg (millimeters of mercury)
• Systolic Pulmonary Arterial Pressure (SPAP) ≥ 60mmHg (millimeters of mercury)
• Cardiovascular collapse, as manifested by inability to achieve a mean arterial pressure (MAP) of 65 mmHg with vasopressor therapy.

Sponsors & Collaborators

• Samuel Brown: lead
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (1)

Intermountain Medical Center

Murray, Utah, 84107, United States

RECRUITING

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

• Samuel M Brown, MD MS

  Intermountain Health Care, Inc.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valerie T Aston, MBA

CONTACT

(801) 507-4606; valerie.aston@imail.org

David P Tomer, MS

CONTACT

(801) 507-4694; David.Tomer@imail.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Pulmonary and Critical Care Medicine

Study Record Dates

• First Submitted: July 2, 2017
• First Posted: July 5, 2017
• Study Start: August 7, 2017
• Primary Completion: December 1, 2020
• Study Completion: June 1, 2021
• Last Updated: February 26, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR, ANALYTIC CODE

Locations

US (1)