Pilot Phase II Study: Hemodynamic Tolerance and Anti-inflammatory Effects of Esmolol During the Treatment of Septic Shock

NCT02120404 | Unknown Phase 2 DMC

• 2 other identifiers: P1209122013-005174-22
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is : \- to evaluate the hemodynamic tolerance of esmolol titrated to obtain a lowering of heart rate of 10% or 20%.

Conditions

Septic Shock

Keywords

septic shock, hemodynamic tolerance, esmolol

Outcome Measures

Primary Outcomes (2)

• Comparison of hemodynamic parameters between 3 groups

  3 groups: GC, G10 and G20. The hemodynamic tolerance will be considered as satisfactory if the variation of MAP and cardiac output induced by esmolol does not exceed 15% of baseline (H0).

  24 hours

• Immunomodulatory effect

  Immunomodulatory effect of esmolol will be evaluated notably by the ratio of IL6 / IL10. The decrease of this ratio in comparison with the value at baseline (H0) will be considered as an indicator of esmolol efficacy as immunomodulator.

  24 hours

Secondary Outcomes (4)

• Comparison of number and severity of organ failures, between the 3 groups

  28 days

• Comparison of autonomic nervous system activity between the 3 groups

  24 hours

• Comparison of mortality in the 3 groups

  28 days

• Comparison in the 3 groups of the correlations between the biomarkers and the hemodynamic data

  24 hours

Study Arms (3)

Control group (GC)

NO INTERVENTION

Control group: no esmolol administration

Group 10 (G10)

EXPERIMENTAL

Esmolol titrated in order to reduce heart rate by 10% as compared to baseline heart rate

Drug: Esmolol administration

Group 20 (G20)

EXPERIMENTAL

Esmolol titrated in order to reduce heart rate by 20% as compared to baseline heart rate

Drug: Esmolol administration

Interventions

Esmolol administration DRUG

Esmolol will be administered during 24 hours, beginning with a titration period to determine the minimal dose allowing to achieve the randomized heart rate reduction of 10% or 20%, as defined by randomization. Titration will be performed in sequences of increasing doses, beginning with 5 μg/kg/min as initial dose, and increasing by 5 μg/kg/min each 30 minutes until the target heart rate reduction is obtained. The maximum dose is 200 μg/kg/min. The titrated dose will be maintained for a total duration of 24 hours.

Also known as: BREVIBLOC 10 mg/ml

Group 10 (G10); Group 20 (G20)

Eligibility Criteria

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

You may qualify if:

• Patient aged ≥ 18 years;
• Patient with septic shock;
• Patient with arterial catheter, central venous catheter with PVC and PiCCO;
• Consent signed by patient. In the absence of a consent signed by patient himself, a consent by a family member will be sought. As soon as possible, the patient will be informed and asked to sign a consent for continuing of study;
• Hemodynamic stability of patient during 1 hour without change in norepinephrine dosage;
• Treatment with noradrenaline for less than 48 hours.

You may not qualify if:

• Need of noradrenaline \> 3 mg/h;
• Treatment with dobutamine;
• Personal history of severe asthma;
• Personal history of severe chronic obstructive pulmonary disease;
• Personal history of pulmonary hypertension;
• Personal history of second degree or third degree atrioventricular block without pacemaker;
• Personal history of sinoatrial block without pacemaker;
• Chronic heart failure with ejection fraction \< 40%;
• Severe atrioventricular nodal bradycardia (heart rate \< 70 bpm);
• Mean arterial pressure \< 65 mm Hg;
• Hypersensitivity to esmolol;
• Prinzmetal angina;
• Pheochromocytoma without treatment;
• Pregnancy woman;
• Breastfeeding woman;

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Baxter Healthcare Corporation: collaborator

Study Sites (1)

ICU, Hôpital Raymond Poincaré

Garches, Haute Des Seine, 92380, France

Location

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

• Djillali ANNANE, MD, PhD

  ICU, Hôpital Raymond Poincaré, 92380 Garches, France

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 18, 2014
• First Posted: April 22, 2014
• Study Start: April 1, 2015
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: August 31, 2023

Record last verified: 2023-08

Locations

FR (1)