Dexmedetomidine and Vasopressin in Septic Shock (DecatSepsis-2)

Dexmedetomidine and Vasopressin (DEX-PRESSIN) for Reducing In-hospital Mortality in Septic Shock Patients: A Protocol for Randomized Controlled Trial (DecatSepsis-2)

Rudiger and Singer suggested strategies for refining adrenergic stress (decatecholaminization). They proposed the use of dexmedetomidine and vasopressin to reduce the catecholamine load during sepsis. The investigators will use vasopressin as the primary vasopressor and a heart rate-calibrated dexmedetomidine infusion in septic shock patients.

The investigators of the current study will use DEXPRESSIN in septic shock patients to investigate the effects of decatecholaminization on in-hospital mortality.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Drug: DEX-PRESSIN; Drug: Standard of Care

Detailed Description

The investigator will include 260 patients with septic shock. The study will compare the use of vasopressin as the first-line vasopressor in septic shock in addition to the dexmedetomidine infusion as in the DecatSepsis trial versus the standard of care. The standard of care is guided by the Surviving Sepsis campaign in 2021.

The main outcomes of the study are in-hospital mortality, norepinephrine equivalent dose, ICU scores, and inflammatory markers.

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Moataz M Emara; Phone Number: +201064048848; Email: mm.emara@mans.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients who develop septic shock in whom a vasopressor is initiated to maintain a mean arterial blood pressure (MAP) of ≥65 mmHg in the presence 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 g/dL at the time of inclusion
• Severe cardiac dysfunction [i.e., ejection fraction (EF) <30%]
• History of heart block or patient on pacemaker
• Severe valvular heart disease
• Chronic liver disease (Child-Pugh classification C)
• Pregnancy
• Patients with traumatic brain injury

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEX-PRESSIN; This group will receive vasopressin as the first-line vasopressor. DEX will be started after hemodynamic stabilization if the heart rate is >90 beats per minute (bpm). NE infusion will be the second-line vasoactive drug.	Drug: DEX-PRESSIN; This group will receive vasopressin as the first-line vasopressor. DEX will be started after hemodynamic stabilization if the heart rate is >90 beats per minute (bpm). NE infusion will be the second-line vasoactive drug.
Active Comparator: Standard-of-care group; This group will receive conventional treatment according to the Surviving Sepsis Campaign 2021 guidelines. This group will receive vasopressin as the second line after NE and will not receive dexmedetomidine.	Drug: Standard of Care; This group will receive conventional treatment according to the SSC 2021 guidelines. This group will receive vasopressin as the second line after NE and will not receive DEX.; Other Names: Control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
in-hospital mortality	All-cause inhospital mortality as a binary outcome	throughout the hospitalization period on average 90 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
survival analysis	time to die using Kaplan Mier Curve	through out the hospitalization period or 28 days after inclusion if discharged from hosptia; before 28 days
Norepinephrine Equivalent Dose (NED)	mean NED over the first three days after enrolment or death, whichever comes first; the NED of epinephrine will be estimated as a 1:1 ratio	over the first three days after enrolment or death
Duration of vasopressor infusion in survivors	Duration in hours from the start of the vasopressor (NE or vasopressin) infusion till the time of discontinuation.	through out the hospitalization period or 28 days after inclusion if discharged from hosptial before 28 days
Initiation of invasive mechanical ventilation (IMV)	incidence of IMV	through out the hospitalization period or 28 days after inclusion if discharged from hosptial before 28 days
Duration of IMV	duratioin in hours	through out the hospitalization period or 28 days after inclusion if discharged from hosptial before 28 days
Early acute kidney injury (AKI)	AKI according to the KDIGO guidelines 2012	within 48 hours
Late acute kidney injury (AKI)	AKI according to the KDIGO guidelines 2012	between 48 hours and 7 days
Acute Physiology and Chronic Health Evaluation (APACHE-II)	As a score on MedCalc	on the 3rd day after enrollment
Simplified Acute Physiology Score (SAPS) II score	As a score on MedCalc	on the 3rd day after enrollment
ICU length of stay	duration in days in survivors	during hospitalization period on average 90 days
Hospital length of stay	duration in days in survivors	during hospitlaization period on average 90 days

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Principal Investigator: Moataz M Emara, Mansoura University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: February 25, 2024
• First Submitted That Met QC Criteria: March 8, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: MS.111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Unidentified individual patients' data will be available with the prinicpal investigator on reasonable request after approval by the local IRB.
• IPD Sharing Time Frame: within 5 years after the study
• IPD Sharing Access Criteria: Undecided
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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