Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP Trial)

Study Overview
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Brief Summary
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The purpose of this trial is to determine the influence of colloid versus crystalloid volume resuscitation and of intensive vs conventional insulin therapy on morbidity and mortality of patients with severe sepsis and septic shock.

Detailed Description
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Severe sepsis and septic shock have a high mortality. Research has concentrated on adjunctive sepsis therapies; the role of supportive measures is comparatively unclear. In Europe the use of colloids is widespread, but there is no evidence on the role of either crystalloid or colloid volume therapy in sepsis. Recently, a higher incidence of kidney failure in sepsis was reported after administration of colloids. In critical illness, a significant reduction in mortality was recently achieved by strict glycemic control, however it has to be determined whether this is true and safe for patients with sepsis as well.

Official Title
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Prospective Randomized Multicenter Study on the Influence of Colloid vs Crystalloid Volume Resuscitation and of Intensive vs Conventional Insulin Therapy on Outcome in Patients With Severe Sepsis and Septic Shock

Conditions
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Severe Sepsis, Septic Shock

Intervention / Treatment
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* Drug: 10% Hemohes® (10% Hydroxyethyl starch)
* Drug: Sterofundin® (Ringer lactate solution)
* Drug: Actrapid® (Insulin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients fulfilling the criteria of severe sepsis or septic shock according to the Society of Critical Care Medicine/American College of Chest Physicians (SCCM/ACCP) definitions not longer than 24 hours before ICU admission or 12 hours after ICU admission Exclusion Criteria: Age < 18 years Pregnancy Known allergy against hydroxyethyl starch Pre-treatment with > 1000ml hydroxyethyl starch within 24 hours before inclusion Pre-existing kidney failure requiring dialysis or serum creatinine value > 320 mmol/l (3,6 mg/dl) Intracerebral hemorrhage Severe head trauma with edema FiO2 at time of study inclusion > 0,7 Heart failure (New York Heart Association [NYHA] IV) Enrolment in another interventional study Immune suppression (cytostatic chemotherapy, steroid therapy, AIDS) Do not resuscitate (DNR) order

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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 10% Hemohes® (10% Hydroxyethyl starch)|nan|
|Drug: Sterofundin® (Ringer lactate solution)|nan|
|Drug: Actrapid® (Insulin)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality (28 day) |  |  | 
| Morbidity (mean sepsis-related organ failure assessment [SOFA] score during intensive care unit length of stay [ICU LOS]) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of acute kidney failure |  |  | 
| Time until hemodynamic stabilization |  |  | 
| Frequency of therapy with vasopressors (in days) |  |  | 
| Course of SOFA sub-scores |  |  | 
| Frequency of hemorrhages under hydroxyethyl starch (HES) therapy |  |  | 
| Frequency of hypoglycemia under intensive insulin therapy |  |  | 
| Frequency of critical illness polyneuropathy (CIP) |  |  | 
| 90 day Mortality |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe sepsis, septic shock, volume substitution, intensive insulin therapy, colloids, crystalloids, outcome, safety