Hydrocortisone for Prevention of Septic Shock

Study Overview
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Brief Summary
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Severe sepsis is a disease with a high mortality. Development of shock is a most serious complication and increases the risk of death considerably. Application of low dose hydrocortisone is currently recommended only in patients after severe septic shock has been established. Hydrocortisone therapy has a hemodynamic stabilizing effect and may reverse shock, however, the preventive application has not been investigated in a larger study. The study investigates whether low dose hydrocortisone prevents the development of shock in patients with severe sepsis. It is postulated that shock prevention may also affect morbidity and mortality.

Official Title
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Placebo-controlled, Randomised, Double-blind Study to Investigate the Efficacy and Safety of Low Dose Hydrocortisone to Prevent the Development of Septic Shock in Patients With Severe Sepsis

Conditions
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Severe Sepsis

Intervention / Treatment
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* Drug: Placebo
* Drug: Hydrocortisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe sepsis according to ACCP/CCM criteria Onset of severe sepsis < 48 hours Informed consent Effective contraception in fertile women Exclusion Criteria: Septic shock Known hypersensitivity to hydrocortisone and additives Glucocorticoid history which warrants continuation of glucocorticoid administration Other indication for systemic glucocorticoid therapy DNR-order Moribund patient Pregnancy Breast feeding women Age < 18 years Other interventional study Relationship to investigator

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydrocortisone<br> | Drug: Hydrocortisone<br>* 50 mg loading dose, continuous infusion of 200 mg/d for 5 d, 100 mg/d for 2d, 50 mg/d for 2 d, and 25 mg/d for 2 d.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Application is identical to experimental arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Septic shock |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | 28, 90, and 180 days; ICU and hospital | 
| Length of stay |  | ICU and hospital (3-6 months) | 
| Time to death |  | 28, 90, and 180 days | 
| Time to septic shock |  | 14 days | 
| Mechanical ventilation |  | until ICU discharge | 
| Renal replacement therapy |  | until ICU discharge | 
| Organ dysfunction (SOFA score) |  | until ICU discharge but day 14 at maximum | 
| Frequency of weaning failure |  | until ICU discharge | 
| Frequency and severity of muscle weakness |  | until ICU discharge | 
| Frequency of gastrointestinal bleeding |  | 28 days | 
| Frequency of secondary infections |  | 28 days | 
| Delir |  | ICU discharge | 
| Hypernatremia |  | 14 days | 
| Hyperglycemia |  | 14 days | 
| Other adverse events |  | 28 days | 
| Posttraumatic stress disorder / health-related quality of life |  | Hosptal discharge and 180 days after hospital discharge | 
| Immune response to hydrocortisone |  | 6 days | 
| Adrenal function |  | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Septic, Shock, Glucocorticoids, Hydrocortisone