Effect of a Continuous Infusion of Esmolol on Stroke Volume in Patients With Hyperdynamic Vasoplegic Septic Shock

NCT02609152 | Withdrawn Phase 3 DMC

• 2 other identifiers: LOCAL/2014/ML-012015-000895-90
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

The main objective of this study is to evaluate the effectiveness of the administration of a short acting beta-blocker in terms of effective increase in stroke volume (at least 15%) after 4 hours initiation of therapy in septic shock in patients with a hyperkinetic profile after 12-24 hours of care. This research seeks to demonstrate that the proportion of patients with an increase in the systolic ejection superior or equal to 15% (relative to baseline) at four hours is different between the two arms of the study: (1) an experimental arm where patients receive an esmolol infusion according to a predetermined procedure and (2) a control arm where patients receive a saline infusion according to a predetermined procedure.

Conditions

Shock, Septic

Outcome Measures

Primary Outcomes (1)

• Is stroke volume increased ≥ 15% as compared to baseline?

  4 hours

Secondary Outcomes (30)

• The time spent with a central venous oxygen saturation between 70% and 80% (minutes)

  4 hours

• Evolution of blood lactate between H0 and H4

  4 hours

• Changes in tissue oxygen saturation compared to baseline

  4 hours

• Ejection fraction of the left ventricle drops below 40% between H0 and H4? yes/no

  4 hours

• the change (in %) of the systolic S wave on the tissue doppler at the mitral annulus relative to baseline

  4 hours

Study Arms (2)

Continuous perfusion of esmolol

EXPERIMENTAL

Intervention: Drug: Continuous perfusion of esmolol

Drug: Continuous perfusion of esmolol

Continuous perfusion of saline

PLACEBO COMPARATOR

Intervention: Continuous perfusion of saline

Drug: Continuous perfusion of saline

Interventions

Continuous perfusion of esmolol DRUG

In the experimental arm of the study, a continuous perfusion of esmolol will be performed. This infusion starts at 5 ml / h with an increase of 5 ml / hr every 10 minutes to obtain a 15% decrease in heart rate. The infusion will be reduced by 5 ml / h every 5 minutes if the cardiac rate is less than 90 beats per minute and stopped if it is less than 70 beats per minute. At H4, the doctor in charge is free to gradually continue or stop the infusion.

Continuous perfusion of esmolol

Continuous perfusion of saline DRUG

In the control arm of the study, a continuous infusion of normal saline will be performed. This infusion starts at 5 ml / h with an increase of 5 ml / hr every 10 minutes to obtain a 15% decrease in heart rate. The infusion will be reduced by 5 ml / h every 5 minutes if the cardiac rate is less than 90 beats per minute and stopped if it is less than 70 beats per minute. A H4, the doctor in charge is free to gradually continue or stop the infusion.

Continuous perfusion of saline

Eligibility Criteria

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

You may qualify if:

• The patient or his/her representative was informed about the implementation of the study, its objectives, constraints and patient rights or emergency consent
• The patient or his/her representative must haven given free and informed consent and signed the consent or emergency consent
• The patient must be affiliated with or the recipient of a health insurance plan
• Septic shock criteria: shock for which the suspected or proven starting point is an infection requiring vasopressors after adequate fluid resuscitation that started within the past 24 to 72 hours
• Precharge independence criteria obtained: i.e. pulsed pressure variation \<13% or variation in ejection volume \<10% or variation in the cardiac index after passive lift leg \<10% or central venous pressure between 8 and 12 mmHg.
• Antibiotic treatment in progress
• Prescription ongoing vasopressor for 24 to 72 hours.
• Sinus rhythm
• Heart rate \> 100 beats per minute
• Cardiac Index measured by thermodilution greater than 4.0 l / min / m\^2
• Central venous oxygen saturation \> 80% without positive inotropics such as dobutamine or isoproterenol (continuously taken or measured via central venous line in superior vena cava territory) on two successive samples in 12 hours
• Monitoring of stroke volume (invasive, semi-invasive or ultrasound)

You may not qualify if:

• The patient is participating in another study
• The patient has participated in another study in the last 3 months
• The patient is under any kind of guardianship
• The patient is under judicial protection
• The patient or his/her representative refuses to sign the consent
• It is impossible to correctly inform the patient
• The patient is pregnant, parturient, or breastfeeding
• The patient has a contraindication for a treatment used in this study
• Cardiac index \< 4.0 l / min / m\^2
• Need to introduce a positive inotropic agent (as determined by the physician in charge of the patient)
• Contraindications to the use of esmolol: Severe sinus bradycardia (less than 50 beats per minute); Sinus pathologies, severe disorders of atrioventricular conduction (without pacemaker), atrioventricular blocks of second and third degree; Cardiogenic shock; Severe hypotension; Decompensated heart failure; Untreated pheochromocytoma; Pulmonary hypertension; Acute asthma attack; chronic obstructive pulmonary disease; peripheral arterial disease; Metabolic acidosis; Known hypersensitivity to esmolol.
• Patient with kidney failure (RIFLE Stage L)
• Chronic treatment with beta blocker
• Patient with ultrasound assessment of left ventricular ejection fraction \< 40%

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (2)

APHM - Hôpital Nord

Marseille, 13915, France

Location

CHRU de Nîmes - Hôpital Universitaire Carémeau

Nîmes, 30029, France

Location

MeSH Terms

Conditions

Shock, Septic

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Marc Leone, MD, PhD

  Centre Hospitalier Universitaire de Nîmes

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2015
• First Posted: November 20, 2015
• Study Start: July 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: August 1, 2017
• Last Updated: May 17, 2018

Record last verified: 2018-05

Locations

FR (2)