Severe Sepsis
Conditions
Keywords
Sepsis, Septic, Shock, Glucocorticoids, Hydrocortisone
Brief summary
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.
Interventions
DRUGPlacebo
Application is identical to experimental arm
DRUGHydrocortisone
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.
Sponsors
German Federal Ministry of Education and Research
SepNet - Critical Care Trials Group
Coordination Centre for Clinical Trials Leipzig
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Septic shock | 14 days |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Mortality | 28, 90, and 180 days; ICU and hospital |
| 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 |
| Frequency of gastrointestinal bleeding | 28 days |
Countries
Germany
Outcome results
None listed