Early Versus Conventional Cessation of Hydrocortisone in Septic Shock (CESSHYDRO)

Composite Adverse Events Compared Early Versus Conventional Cessation of Hydrocortisone in Patients With Septic Shock: Randomized-controlled Trial

Septic shock is one of the causes of death in ICU and hospital. Refractory shock is the problem which healthcare providers should recognize though it is difficult to handle with. The corticosteroid called hydrocortisone is one of the treatment in refractory septic shock which requires vasopressor to maintain blood pressure. In recovery phase of septic shock and weaning off vasopressor, there is no definite way to taper off hydrocortisone.

Study Overview

• Status: Recruiting
• Conditions: Hyperglycemia; Septic Shock; Muscle Weakness; Hypernatremia; Adverse Event; Hydrocortisone; Superimposed Infection
• Intervention / Treatment: Drug: normal saline solution; Drug: Hydrocortisone and normal saline solution

Detailed Description

According to secondary outcomes of several studies analyzed in systemic review was shown adverse events from corticosteroid uses including hyperglycemia, hypernatremia, muscle weakness, and superimposed infection. This trials will compare composite adverse events in early versus conventional cessation of hydrocortisone in septic shock.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Surat Tongyoo, Doctor; Phone Number: +24197764; Email: surat.ton@mahidol.ac.th
• Study Contact Backup: Name: Kolanya Kangwanyotsak, Doctor; Phone Number: +24197764; Email: tkolanya@hotmail.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University
    • Contact: Surat Tongyoo, MD; Phone Number: +6624197764; Email: surat.ton@mahidol.ac.th
    • Contact: Kolanya Kangwanyotsak, MD; Phone Number: +66875656234; Email: tkolanya@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient >= 18 years old
• Diagnosis Septic shock from the definition of SEPSIS III criteria in intensive care unit or medicine ward or surgical ward at Siriraj hospital
• Received at least 1 catecholamines and hydrocortisone at least 200 mg/d
• Maintain mean arterial pressure >= 65 mmHg even if titrate down catecholamines until low dose (<=0.1 mcg/kg/min)

Exclusion Criteria:

• Patient sign Do not resuscitation and terminally ill
• Pregnancy
• Need long term steroid use due to other medical condition

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: early cessation group; The pharmacist uses 100 ml of normal saline solution, packed out in the same format, dose, and administration of the drug were exactly the same as in the conventional cessation group. The experimental starts after required dose of vasopressor less than 0.1 mcg/kg/min. The nurse serially records capillary blood glucose and serum sodium following the doctor's order.	Drug: normal saline solution; Prepare 100 ml of normal saline solution, packed out in the same format, dose, and administration of the drug were exactly the same as in the conventional cessation group.; Other Names: early cessation group
Placebo Comparator: conventional cessation group; The pharmacist prepared hydrocortisone and normal saline solution 100 ml starts dose at least 200 mg/day according to doctor's order after patient meets the criteria of refractory septic shock then continues conventional cessation of hydrocortisone according to doctor's order after required dose of vasopressor less than 0.1 mcg/kg/min. The nurse serially records capillary blood glucose and serum sodium following the doctor's order.	Drug: Hydrocortisone and normal saline solution; Prepare hydrocortisone with normal saline solution 100 ml starts dose at least 200 mg/day according to doctor's order after patient meets the criteria of refractory septic shock then continues conventional cessation of hydrocortisone according to doctor's order after required dose of vasopressor less than 0.1 mcg/kg/min.; Other Names: conventional cessation group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite adverse events of early versus conventional cessation of hydrocortisone	including level of capillary blood glucose >= 180mg/dL(Hyperglycemia) , Plasma level of sodium>= 150mmol/L(Hypernatremia), new onset of infection , and neuromuscular weakness(muscular impairment rating scale>1	within 14 days after randomization or until discharge from hospital, whichever came first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with 28-day mortality from any cause or until discharge from hospital	death from any cause until 28-day after randomization or until discharge from hospital	28-day mortality from any cause start until 28 day after randomization or until discharge from hospital, whichever came first
Concentration of insulin needed due to hyperglycemia	Total insulin used to lower capillary blood sugar if level of glucose more than 180 mg/dL	within 14 days after randomization or until discharge from hospital, whichever came first
Number of participants with hypoglycemia	Number of participants with capillary blood glucose < 80 mg/dL	within 14 days after randomization or until discharge from hospital, whichever came first
Number of participants with capillary blood glucose ≥ 150 mg/dL	Number of participants with capillary blood glucose ≥ 150 mg/dL	within 14 days after randomization or until discharge from hospital, whichever came first
Time of vasopressor reinitiation until 14 day after randomization or until hospital discharge	Duration measured as hours from off vasopressor until re-initiation at least 0.05 mcg/kg/min until 14 day after randomization or until hospital discharge	within 14 days after randomization or until discharge from hospital, whichever came first
Time to need of fluid bolus	Duration measured as hours from randomization until fluid bolus at least 250 ml in 10-15 minutes until 14 day after randomization or until hospital discharge	within 14 days after randomization or until discharge from hospital, whichever came first
Time to reversal of shock	Duration measured as hours from randomization until off vasopressor	within 14 days after first dose of hydrocortisone or until discharge from hospital, whichever came first
Number of participants with New onset of infection within 28 days	Number of participants with New onset of infection within 28 days	28 days
Duration of ICU length of stay	Duration measured as days from randomization until discharge from ICU	14 days after first dose hydrocortisone or until discharge from hospital, whichever came first
Duration of Ventilator free day	Duration measured as hours from off ventilator until on ventilator or reintubation	14 days after first dose hydrocortisone or until discharge from hospital, whichever came first
Number of participants with Lung injury score at day 1, day 3, day 7 after first dose hydrocortisone	Number of participants with Lung injury score at day1, day3, day7 after first dose hydrocortisone	7 days after randomization or until discharge from hospital, whichever came first
Level of minimum and maximum mean arterial pressure	Level of minimum and maximum mean arterial pressure until 14 days after randomization or until hospital discharge	within 14 days after randomization or until discharge from hospital, whichever came first
Number of participants with Alive days in 28 days with free mechanical ventilator	Number of participants who survive in 28 days with free mechanical ventilator	28 days after randomization or until discharge from hospital, whichever came first
Number of participants with Alive days in 28 days with free renal replacement therapy	Number of participants who survive in 28 days with free mechanical ventilator	28 days after randomization or until discharge from hospital, whichever came first
Number of participants with Alive days in 28 days with free organ supports	Number of participants who survive in 28 days with free mechanical ventilator	28 days after randomization or until discharge from hospital, whichever came first

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Principal Investigator: Surat Tongyoo, Doctor, Mahidol University

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: March 19, 2023
• First Submitted That Met QC Criteria: April 18, 2023
• First Posted (Actual): April 19, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: muscle weakness; septic shock; hyperglycemia; hydrocortisone; hypernatremia; composite adverse events; superimposed infection
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Sepsis; Neuromuscular Manifestations; Water-Electrolyte Imbalance; Opportunistic Infections; Hyperglycemia; Shock, Septic; Muscle Weakness; Shock; Paresis; Hypernatremia; Superinfection; Anti-Inflammatory Agents; Pharmaceutical Solutions; Hydrocortisone
• Other Study ID Numbers: SI 012/2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymous identification data will be prepared per request, after study publication 6 months
• IPD Sharing Time Frame: 6 months post study publication
• IPD Sharing Access Criteria: Request to principal investigation, after protocol approval from ethical committee
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

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.: Yes