Effects of Voluven on Hemodynamics and Tolerability of Enteral Nutrition in Patients With Severe Sepsis

Study Overview
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Brief Summary
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The rapidity and the quality of fluid resuscitation in patients with severe sepsis are important factors for the prevention of secondary multi-organ failure. Vascular filling may also have an impact on tolerability of enteral nutrition. The earliness and quantity of calories provided by enteral nutrition may have an impact on morbidity and mortality. This study will asses the effects of volume expansion on hemodynamics and tolerability of enteral nutrition in patients with severe sepsis. A Data Monitoring Committee will review regularly safety data of the study.

Official Title
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Effects of Voluven on Hemodynamics and Tolerability of Enteral Nutrition in Patients With Severe Sepsis

Conditions
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Sepsis

Intervention / Treatment
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* Drug: 6 % Hydroxyethylstarch 130/0.4 = Voluven®
* Drug: 0.9 % NaCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe sepsis Requirement for fluid resuscitation Exclusion Criteria: serum creatinine > 300µmol/L Chronic renal failure Anuria lasting more than 4 hours Requirement for renal support

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: Voluven® Arm<br> | Drug: 6 % Hydroxyethylstarch 130/0.4 = Voluven®<br>* Voluven® was administered intravenously. Voluven® rates were not to exceed 50 mL/kg/day on the first day and 25 mL/kg/day on the second to fourth days, according to patient needs.<br>* Other names: Voluven®;|
| Active Comparator: 0.9 % NaCl<br> | Drug: 0.9 % NaCl<br>* NaCl 0.9 % was administered intravenously. NaCl 0.9% rates were not to exceed 50 mL/kg/day on the first day and 25 mL/kg/day from the second to the fourth day, according to patient needs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of Study Drug Required to Achieve Initial Hemodynamic Stabilization | Initial hemodynamic stabilization (HDS) was defined as normalization of mean arterial pressure (MAP) and at least two of the three parameters central venous pressure (CVP), urine output and central venous oxygen saturation and maintaining this normalization over a period of four hours, with no increase in the infusion of vasopressors, or ionotropic therapy and with no more than 1 L of additional study drug administration within these four hours. | until hemodynamic stabilization (up to 48 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Start of Fluid Resuscitation With Study Drug to the Initial Hemodynamic Stabilization | Time from start of fluid resuscitation with study drug to the initial hemodynamic stabilization | until hemodynamic stabilization (up to 48 hours) | 
| Quantity of Study Drug in 4 Days | Total quantity of study drug infused over four consecutive days in the ICU | 4 days | 
| Time From Start of Study Drug to Start of Enteral Nutrition in the Subgroup of Patients Who Received Enteral Nutrition | Time from start of fluid resuscitation with study drug to start of enteral nutrition. | Until start of enteral nutrition (up to 48 hours) | 
| Time From Start of Fluid Resuscitation With Study Drug to Start of Enteral Nutrition After Hemodynamic Stabilization | Administration of enteral nutrition before initial hemodynamic stabilization was ignored in this analysis. | up to 48 hours | 
| Total Amount of Enteral Calories During the First Seven Days of Enteral Nutrition | This amount will be calculated from start of enteral nutrition until 7 am of day 8 | 7 days | 
| Length of Stay in the Intensive Care Unit (ICU) | Length of stay was analysed in two approaches. First, it was calculated and analysed only for patients who did not die before end of study of the individual patient. As a sensitivity analysis, the analysis was carried out including patients who died with the maximum possible length of stay (i.e., the worst possible value). | Until discharge from ICU (up to day 90) | 
| Length of Stay in the ICU | Length of stay was analysed in two approaches. First, it was calculated and analysed only for patients who did not die before end of study of the individual patient. As a sensitivity analysis, the analysis was carried out including patients who died with the maximum possible length of stay (i.e., worst possible value). | Until discharge from ICU (up to Day 90) | 
| Length of Stay in the Hospital | Length of stay was analysed in two approaches. First, it was calculated and analysed only for patients who did not die before end of study of the individual patient. As a sensitivity analysis, the analysis was carried out including patients who died with the maximum possible length of stay (i.e., the worst possible value). | Until discharge from hospital (up to day 90) | 
| Area Under the Curve (AUC) of Sepsis-related Organ Failure Assessment (SOFA) Score Per Day From Screening to Day 4 | The Sepsis-related Organ Failure Assessment (SOFA) score in this study is reported for entire days, not for exact time points on a day. Potentially, more than one SOFA score may be available for the same day. In this case, the mean of the respective total scores was used for that day for calculation of Area Under the Curve (AUC). The SOFA score includes sub-scores for Respiration, Coagulation, Liver, Cardiovascular, Central Nervous System and Renal function and may range from 0 (worst outcome) to 4 (best outcome). | From Screening to Day 4 |