Septic ShockPhase 2ECASSS-RNCT02841241
Esmolol Infusion for Patients With Septic Shock and Persistent Tachycardia
A Phase 2 study testing Esmolol in people with Septic Shock, run by Intermountain Health Care, Inc. at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Esmolol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to Mar 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Within 48 hours of admission to the ICU and septic shock (sepsis present at time of admission)
- 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.
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- 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).
Who cannot join
- 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.
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- 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.
- Cardiogenic shock, as defined by any of the following
- Cardiac index ≤ 2 L/min/m2
- Ejection fraction ≤ 25%
- ScvO2 ≤ 60%
- Current infusion of any dose of dobutamine, milrinone, or dopamine
- Current infusion of epinephrine for clinically diagnosed cardiogenic shock
- Significant atrioventricular dysfunction
- Sick sinus syndrome
- PR interval (time from onset of P wave to start of QRS complex) > 200 msec
- Current evidence or prior history of Grade 2 or Grade 3 heart block
- Pacemaker or plans to place a pacemaker
- Pheochromocytoma or status asthmaticus
- Receiving clonidine, guanfacine, or moxonidine
- Hemoglobin < 7 gm/dl
- Cardiovascular collapse (failure to achieve MAP of 65mmHg)
- Cardiac arrest within 24 hours
- 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.
- Worse than mild mitral stenosis • Known mitral stenosis, with any of (1) valve area ≤ 1.5 cm2 OR mean gradient ≥ 5 mmHg.
Trial locations and contacts
1 site in 1 country.
United States1 site
Intermountain Medical Center and Intermountain Clinics
Murray, Utah, 84143
About this study
Official title: Esmolol to Control Adrenergic Storm in Septic Shock - Roll-in
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.
Read the detailed description
PRIMARY OBJECTIVE:
To evaluate the adequacy and efficiency of study protocols for the anticipated, randomized, controlled ECASSS study. The primary clinical outcome is organ-failure free days at 28 days, with multiple secondary outcomes, including those relevant to function of and compliance with the study protocols.
- Conditions
- Septic Shock
- Being tested
- Esmolol
- Keywords
- esmolol, adrenergic storm, septic shock
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsmololDrug
Also called Brevibloc
Esmolol infusion
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Esmolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Day 28
Secondary outcomes (4)
All-cause Mortality
Measured: 90 days
Peak Serum High-sensitivity Troponin
Measured after enrollment.
Measured: 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
Measured: Day 1
Development of Heart Block
Measured: for duration of esmolol infusion, an expected average of 2 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2016 (estimated)
- Study startApr 2016
- Primary completionMar 2017
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intermountain Health Care, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center
- Responsible party
- Sponsor
- Investigators
- Samuel Brown, MD,MS, Principal investigator, Intermountain Health Care, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02841241
- Sponsor's protocol ID
- 1050147
- Acronym
- ECASSS-R
- Status last verified
- Dec 2018
- First submitted
- 14 Jul 2016
- Last updated
- 9 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Rudiger A, Singer M. The heart in sepsis: from basic mechanisms to clinical management. Curr Vasc Pharmacol. 2013 Mar 1;11(2):187-95.
PubMed 23506497Novotny 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.
PubMed 18636043Oberbeck 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.
PubMed 19275613Morelli 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.
PubMed 24108526Brown 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.
PubMed 30123523
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Esmolol to Control Adrenergic Storm in Septic Shock - Roll-in
- ClinicalTrials.gov ID
- NCT02841241
- Acronym / sponsor ID
- ECASSS-R / 1050147
- Conditions
- Septic Shock
- Keywords
- esmolol, adrenergic storm, septic shock
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Intermountain Health Care, Inc.University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center
- Study start
- Apr 2016
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 22 Jul 2016 (estimated)
- Results
- Posted 9 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
To evaluate the adequacy and efficiency of study protocols for the anticipated, randomized, controlled ECASSS study. The primary clinical outcome is organ-failure free days at 28 days, with multiple secondary outcomes, including those relevant to function of and compliance with the study protocols.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Esmolol | Experimental | Drug: EsmololEsmolol infusion, started without bolus, with slow upward titration to a maximum infusion rate is protocolized, with a target heart rate of 80-90/min |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 years
- Within 48 hours of admission to the ICU and septic shock (sepsis present at time of admission)
- 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.
Key exclusion criteria (34 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EsmololAlso: BreviblocEsmolol infusion | Drug | Esmolol |
Primary outcome
Organ-failure-free Days
Time frame: Day 28
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)
4 secondary outcomes
All-cause Mortality
Time frame: 90 days
Peak Serum High-sensitivity Troponin
Time frame: 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
Time frame: Day 1
Development of Heart Block
Time frame: for duration of esmolol infusion, an expected average of 2 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23506497Rudiger A, Singer M. The heart in sepsis: from basic mechanisms to clinical management. Curr Vasc Pharmacol. 2013 Mar 1;11(2):187-95.
- Background: PubMed 18636043Novotny 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.
- Background: PubMed 19275613Oberbeck 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.
- Background: PubMed 24108526Morelli 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.
- Derived from this study: PubMed 30123523Brown 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.
- Esmolol infusion in patients with septic shock and tachycardia: a prospective, single-arm, feasibility studyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel Brown, MD,MS principal investigator
Intermountain Health Care, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Esmolol in people with Septic Shock, run by Intermountain Health Care, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Organ-failure-free Days (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02841241, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2019.