Decatecholaminisation of Septic Shock With Dexmedetomidine and In-hospital Mortality (DECATSepsis)

Decatecholaminisation With Dexmedetomidine for Reduction of Mortality in Septic Shock: A Randomized Clinical Trial

The study aims to determine whether the infusion of DEX in septic shock can reduce in-hospital mortality, norepinephrine infusion, need and duration for mechanical ventilation, and acute kidney injury without significant adverse events.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Drug: Dexmedetomidine

Detailed Description

During septic shock, acute stress response includes neural and humoral autonomic flaring, which tend to be beneficial in the short term. Once shock occurs, it is a failure of the compensation trial. In addition, chronic autonomic stimulation risks myocardial injury, immunosuppression, insulin resistance, and thrombo-embolic tendency.

The investigators hypothesized that dacatecholaminisation with dexmedetomidine - as calibrated by heart rate control - would reduce the in-hospital mortality in septic shock, whether the patient is mechanically ventilated or not. The study aims to determine whether the infusion of DEX in septic shock can reduce in-hospital mortality, norepinephrine infusion, need and duration for mechanical ventilation, and acute kidney injury without significant adverse events.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Moataz M Emara; Phone Number: +20 1064048848; Email: mm.emara@mans.edu.eg
• Study Contact Backup: Name: Ahmed Ragab; Phone Number: +20 1099323347; Email: dr.ezz2712@gmail.com

Study Locations

• Egypt
  • Aldakahlia
    • Mansoura, Aldakahlia, Egypt, 35516
      • Mansoura University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (≥ 18 years) patients of either sex who develop septic shock with heart rate (HR) > 90 beats per minute (bpm).

We choose the definition of septic shock as the start of norepinephrine (NE) infusion to maintain the mean arterial blood pressure (MAP) of ≥ 65 mmHg in a case of sepsis (≥ 2 SIRS criteria plus suspicion or confirmation of infection).

Exclusion Criteria:

• Patient refusal or inability to obtain consent
• Failure of hemodynamic stabilization or hemoglobin < 7 gm/dl at time of inclusion
• Severe cardiac dysfunction (Ejection Fraction (EF) < 30%)
• History of heart block or patient on pacemaker
• Chronic liver Disease (Child-Pugh classification C)
• Severe valvular heart disease
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine; Patients will receive dexmedetomidine infusion according to the protocol plus the usual care. We will evaluate patients for inclusion in the study after 6 hours on NE infusion, given stabilization of the MAP > 65 mmHg. In the DEX group, we will commence DEX infusion at the rate of 0.2 mcg.kg-1.h-1 without a loading dose, then titrate DEX infusion to maintain the HR from 60 to 90 bpm. Titration of the DEX infusion rate will not be more than 0.1 mcg.kg-1.h-1 every 30 minutes at any time. The maximum DEX infusion rate will be 0.7 mcg.kg-1.h-1. We aim to continue DEX infusion for 48 hours. After 48 hours of DEX infusion, we will taper the DEX infusion over one hour. According to our protocol, DEX infusion would trigger either STOP events or hemodynamic assessment events:	Drug: Dexmedetomidine; A highly-selective alpha-2 agonist with sedative, analgesic, and sympatholytic effects.; Other Names: Precedex, Dexdor, Dexdomitor, Sileo
No Intervention: Usual care without dexmedetomidine infusion; The patients in this group will receive the usual care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-hospital mortality	The investigators will review the patient status on discharge from the hospital, alive or dead	Through study completion, an average of 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Norepinephrine equivalent dose (NED)	reported as the average of the serial measurements; the NED of epinephrine will be estimated as 1:1 ratio, reported as mcg/kg/min (Shruti Goradia et al, 2021)	over the first 3 days after enrolment or death, which comes first
Need for epinephrine infusion	Categorical variable (as yes/no outcome)	over the first 3 days after enrolment or death, which comes first
Heart rate (HR) beat per minute	reported as the average of the serial measurements	over the first 3 days after enrolment or death, which comes first
Mean arterial blood pressure (MAP) mmHg	reported as the average of the serial measurements	over the first 3 days after enrolment or death, which comes first
Initiation of invasive mechanical ventilation (IMV) in non-ventilated patients	Categorical variable (as yes/no outcome)	Through study completion, an average of 3 months
Early acute kidney injury	Categorical variable (as yes/no outcome) - as defined by Khwaja, A., 2012. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical Practice, 120(4), pp.c179-c184.	48 hours after ICU admission in previously normal kidney function
Late acute kidney injury	Categorical variable (as yes/no outcome) - as defined by the Khwaja, A., 2012. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical Practice, 120(4), pp.c179-c184.	7 days after ICU admission in previously normal kidney function

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Study Director: Moataz M Emara, MD, EDAIC, Mansoura University Faculty of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2022
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: February 28, 2022
• First Submitted That Met QC Criteria: March 8, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 3, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: randomized controlled trial; dexmedetomidine
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: MS.22.02.1889

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The anonymously patient data will be available on reasonable request - according to the local IRB approval - from the corresponding author and the central study contact, Moataz Emara at mm.emara@mans.edu.eg or mm.emara@yahoo.com.
• IPD Sharing Time Frame: will be shared shortly.
• IPD Sharing Access Criteria: The anonymously patient data will be available on reasonable request - according to the local IRB approval - from the corresponding author and the central study contact, Moataz Emara at mm.emara@mans.edu.eg or mm.emara@yahoo.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes