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

NCT ID: NCT03208257

Last Updated: 2019-02-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-07
• Study Completion Date: 2021-06-30

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.

Detailed Description

This is a prospective, single arm, feasibility study of esmolol infusion in septic shock. The objective is to evaluate the feasibility, adequacy, and efficiency of study protocols for a subsequent ECASSS study. This study (ECASSS-R2) extends observations made in an initial pilot, ECASSS-R.

Conditions

Septic Shock

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Esmolol

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.

Group Type: EXPERIMENTAL

Esmolol

Intervention Type: DRUG

Esmolol hydrochloride infusion

Interventions

Esmolol

Esmolol hydrochloride infusion

Intervention Type: DRUG

Other Intervention Names

BREVIBLOC

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. 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

3. Receiving vasopressors through a central venous catheter for more than 60 minutes.

4. Arterial catheter in place or expected to be placed imminently.

5. Heart rate > 90/min while receiving vasopressors for more than 60 minutes.

6. 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.)

1. Central venous pressure (CVP) > 15 mm Hg.

2. Negative Passive-Leg Raise (PLR) maneuver (<10% increase in cardiac output after PLR).

3. 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]).

4. Inferior vena cava (IVC) plethora

5. 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).

Exclusion Criteria

1. Lack of informed consent.

2. Currently receiving ExtraCorporeal Membrane Oxygenation (ECMO).

3. Known pregnancy or nursing.

4. Patient is a prisoner.

5. Patient on hospice (or equivalent comfort care approach) at or before the time of enrollment.

6. Known or current atrial fibrillation.

7. Previously enrolled in the trial.

8. Known allergy to esmolol or vehicle (see Appendix 2 for BREVIBLOC vehicle ingredients).

9. Receipt of nodal blocking agents (see Appendix 3 for list of such agents) within three half lives

10. Hemoglobin < 7 gm/dl.

11. Cardiac arrest within 24 hours.

12. 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)

13. Cardiovascular collapse, as manifested by inability to achieve a mean arterial pressure (MAP) of 65 mmHg with vasopressor therapy.

14. Cardiogenic shock, as defined by any of the following

• Cardiac index ≤ 2.3 L/min/m2
• Ejection fraction ≤ 30%
• ScvO2 ≤ 60%
• Current infusion of any dose of dobutamine, milrinone, or dopamine (if dopamine is being used for clinically diagnosed bradycardia or cardiogenic shock)
• Current infusion of epinephrine for clinically diagnosed cardiogenic shock

15. Significant atrioventricular dysfunction

• Sick sinus syndrome
• PR interval > 200 msec
• Current evidence or prior history of Grade 2 or Grade 3 heart block
• Pacemaker or plans to place a pacemaker

16. Pheochromocytoma or status asthmaticus

17. Receiving clonidine, guanfacine, or moxonidine

18. Worse than moderate aortic stenosis

• Known aortic stenosis, with any of (1) mean gradient ≥ 40 mmHg OR (2) maximum gradient ≥ 60mmHg OR (3) aortic valve area ≤ 1.0cm2 OR (4) aortic valve area index ≤ 0.85cm2/m2 body surface area.

19. Worse than mild mitral stenosis

• Known mitral stenosis, with any of (1) valve area ≤ 1.5 cm2 OR mean gradient ≥ 5 mmHg.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Samuel Brown

OTHER

Sponsor Role: lead

Responsible Party

Samuel Brown

Associate Professor, Pulmonary and Critical Care Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Samuel M Brown, MD MS

Role: PRINCIPAL_INVESTIGATOR

Intermountain Health Care, Inc.

Locations

Intermountain Medical Center

Murray, Utah, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Valerie T Aston, MBA

Role: CONTACT

valerie.aston@imail.org

(801) 507-4606

David P Tomer, MS

Role: CONTACT

David.Tomer@imail.org

(801) 507-4694

Facility Contacts

Valerie T Aston, MBA

Role: primary

valerie.aston@imail.org

801-507-4606

David P Tomer, MS

Role: backup

David.Tomer@imail.org

(801) 507-4694

Other Identifiers

1050522

Identifier Type: -

Identifier Source: org_study_id