Clinical trial NCT00135473: Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP Trial)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Sepsis
Septic Shock
Keywords: Severe sepsis
septic shock
volume substitution
intensive insulin therapy
colloids
crystalloids
outcome
safety
Lead sponsor: SepNet - Critical Care Trials Group
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
name: B. Braun Melsungen AG
name: Novo Nordisk A/S
name: HemoCue
First posted: 2005-08-26
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mortality (28 day)
measure: Morbidity (mean sepsis-related organ failure assessment [SOFA] score during intensive care unit length of stay [ICU LOS])
Secondary outcomes:
measure: Frequency of acute kidney failure
measure: Time until hemodynamic stabilization
measure: Frequency of therapy with vasopressors (in days)
measure: Course of SOFA sub-scores
measure: Frequency of hemorrhages under hydroxyethyl starch (HES) therapy
measure: Frequency of hypoglycemia under intensive insulin therapy
measure: Frequency of critical illness polyneuropathy (CIP)
measure: 90 day Mortality
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Universitätsklinikum der RWTH Aachen
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Berlin
country: Germany
facility: VIVANTES Klinikum Neukölln II
city: Berlin
country: Germany
facility: Charité I Campus Virchow-Klinikum
city: Brandenburg
country: Germany
facility: Städtisches Klinikum Brandenburg GmbH
city: Dresden
country: Germany
facility: Krankenhaus Dresden Friedrichstadt
city: Dresden
country: Germany
facility: Universität Carl-Gustav-Carus
city: Erfurt
country: Germany
facility: HELIOS Klinikum Erfurt
city: Erlangen
country: Germany
facility: Universität Erlangen-Nürnberg
city: Greifswald
country: Germany
facility: Ernst-Moritz-Arndt-Universität
city: Göttingen
country: Germany
facility: Georg-August-Universität Göttingen
city: Halle/Saale
country: Germany
facility: Martin-Luther-Universität Halle/Wittenberg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Kiel
country: Germany
facility: Universitätsklinikum Kiel
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
Study officials:
affiliation: F.-Schiller-University Jena, Germany
name: Konrad Reinhart, MD
role: STUDY_CHAIR
affiliation: F.-Schiller-University Jena, Germany
name: Thomas Deufel, MD
role: STUDY_DIRECTOR
affiliation: University of Leipzig
name: Markus Löffler, MD
role: STUDY_DIRECTOR
References:
citation: Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K; German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008 Jan 10;358(2):125-39. doi: 10.1056/NEJMoa070716.