Early Versus Conventional Cessation of Hydrocortisone in Septic Shock

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Septic Shock, Adverse Event, Hydrocortisone, Hyperglycemia, Hypernatremia, Muscle Weakness, Superimposed Infection

Intervention / Treatment
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* Drug: normal saline solution
* Drug: Hydrocortisone and normal saline solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pharmacist who does not involve in patient enrollment nor treatment will prepared hydrocortisone or placebo in the identical container, before the study drug will be discontinued from patients , according to their treatment arm.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: early cessation group<br>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<br>* 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.<br>* Other names: early cessation group;|
| Placebo Comparator: conventional cessation group<br>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<br>* 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.<br>* Other names: conventional cessation group;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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septic shock, composite adverse events, hydrocortisone, hyperglycemia, hypernatremia, muscle weakness, superimposed infection