Esmolol Infusion for Patients With Septic Shock and Persistent Tachycardia

NCT02841241 | Completed Phase 2 Results DMC

• 1 other identifier: 1050147
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single arm, "roll-in" study of esmolol infusion for patients with septic shock with persistent tachycardia after adequate intravenous volume expansion. The study will evaluate the adequacy and efficiency of study protocols for the anticipated, main ECASSS study, which will have a separate entry in clinicaltrials.gov.

Conditions

Septic Shock

Keywords

esmolol; adrenergic storm; septic shock

Outcome Measures

Primary Outcomes (1)

• Organ-failure-free Days

  As of day 28, the number of calendar days on which the patient receives none of (a) vasopressor therapy, (b) mechanical ventilation, or (c) renal replacement therapy. If the patients dies on or before day 28, they have -1 organ-failure-free days. The resulting point-based score combines the probability of death and the number of days without organ failure. Score of -1 = Death before day 28 (Lowest Score). Score of 28 = Patient has been successful at going 28 without any vasopressor therapy/mechanical ventilation/renal replacement therapy (Highest Score)

  Day 28

Secondary Outcomes (4)

• All-cause Mortality

  90 days

• Peak Serum High-sensitivity Troponin

  Troponin is measured on day 0 and day 1 (first day of esmolol infusion is day 0)

• Left Ventricular Global Longitudinal Strain at 24 Hours

  Day 1

• Development of Heart Block

  for duration of esmolol infusion, an expected average of 2 days

Other Outcomes (3)

• Proportion of Compliance With Final Safety Check

  Day 0

• Percentage Hourly Checks During Which Protocol Compliance Was Observed

  for duration of esmolol infusion, an expected average of 2 days

• Number of Participants With Intolerance to Esmolol Infusion at Any Given Rate

  duration of esmolol infusion (~2 days)

Study Arms (1)

Esmolol

EXPERIMENTAL

Esmolol infusion, started without bolus, with slow upward titration to a maximum infusion rate is protocolized, with a target heart rate of 80-90/min

Drug: Esmolol

Interventions

Esmolol DRUG

Esmolol 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 48 hours of admission to the ICU and septic shock (sepsis present at time of admission)
• a. Septic shock defined by consensus criteria as i. At least two systemic inflammatory response syndrome (SIRS) criteria ii. Suspected or documented infection iii. 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).
• For patients who happen to be breathing passively on a positive pressure mechanical ventilator delivering at least 8 ml/kg tidal volumes and in normal sinus rhythm, stroke volume variability \<10% (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 ECMO (extracorporeal membrane oxygenation).
• 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
• Receipt of nodal blocking 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 TTE (transthoracic echocardiography) of any of the following
• mPAP (mean pulmonary artery pressure) ≥ 35 mmHg
• SPAP (systolic pulmonary artery pressure)≥ 60 mmHg
• Cardiovascular collapse, as manifested by inability to achieve a MAP (mean arterial pressure) of 65 mmHg with vasopressor therapy.

Sponsors & Collaborators

• Intermountain Health Care, Inc.: lead
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (1)

Intermountain Medical Center and Intermountain Clinics

Murray, Utah, 84143, United States

Location

Related Publications (5)

• Rudiger A, Singer M. The heart in sepsis: from basic mechanisms to clinical management. Curr Vasc Pharmacol. 2013 Mar 1;11(2):187-95.

  PMID: 23506497 BACKGROUND

• Novotny NM, Lahm T, Markel TA, Crisostomo PR, Wang M, Wang Y, Ray R, Tan J, Al-Azzawi D, Meldrum DR. beta-Blockers in sepsis: reexamining the evidence. Shock. 2009 Feb;31(2):113-9. doi: 10.1097/SHK.0b013e318180ffb6.

  PMID: 18636043 BACKGROUND

• Oberbeck R, Kobbe P. Beta-adrenergic antagonists: indications and potential immunomodulatory side effects in the critically ill. Curr Med Chem. 2009;16(9):1082-90. doi: 10.2174/092986709787581770.

  PMID: 19275613 BACKGROUND

• Morelli A, Ertmer C, Westphal M, Rehberg S, Kampmeier T, Ligges S, Orecchioni A, D'Egidio A, D'Ippoliti F, Raffone C, Venditti M, Guarracino F, Girardis M, Tritapepe L, Pietropaoli P, Mebazaa A, Singer M. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013 Oct 23;310(16):1683-91. doi: 10.1001/jama.2013.278477.

  PMID: 24108526 BACKGROUND

• Brown SM, Beesley SJ, Lanspa MJ, Grissom CK, Wilson EL, Parikh SM, Sarge T, Talmor D, Banner-Goodspeed V, Novack V, Thompson BT, Shahul S; Esmolol to Control Adrenergic Storm in Septic Shock-ROLL-IN (ECASSS-R) study. Esmolol infusion in patients with septic shock and tachycardia: a prospective, single-arm, feasibility study. Pilot Feasibility Stud. 2018 Aug 3;4:132. doi: 10.1186/s40814-018-0321-5. eCollection 2018.

  PMID: 30123523 DERIVED

Related Links

• Esmolol infusion in patients with septic shock and tachycardia: a prospective, single-arm, feasibility study

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

Results Point of Contact

• Title: Office of Research
• Organization: Intermountain Medical Center

officeofresearch@imail.org

8015077000

Study Officials

• Samuel Brown, MD,MS

  Intermountain Health Care, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2016
• First Posted: July 22, 2016
• Study Start: April 1, 2016
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: January 9, 2019
• Results First Posted: January 9, 2019

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)