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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00464204
Recruitment Status : Completed
First Posted : April 23, 2007
Results First Posted : August 2, 2011
Last Update Posted : January 11, 2012
Sponsor:
Information provided by (Responsible Party):
Fresenius Kabi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Sepsis
Interventions Drug: 6 % Hydroxyethylstarch 130/0.4 = "Voluven®"
Drug: 0.9 % NaCl
Enrollment 196
Recruitment Details Participants were recruited in 24 intensive care units of hospitals in France and Germany from July 2007 until February 2010 and were followed up until May 2010.
Pre-assignment Details Participants were screened in intensive care units of the participating study sites in France and Germany.
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description 6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day NaCl 0.9 %; 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
Period Title: Overall Study
Started 100 96
Completed Treatment 81 83
Day 30 Follow-up Performed 89 83
Day 90 Follow-up Performed 69 74
Withdrawal Due to Discharge From ICU 18 11
Completed 51 [1] 64 [1]
Not Completed 49 32
[1]
Completed=no withdrawal until day 8.
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm Total
Hide Arm/Group Description 6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day NaCl 0.9 %; 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 Total of all reporting groups
Overall Number of Baseline Participants 100 96 196
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 100 participants 96 participants 196 participants
65.8  (15.4) 65.9  (14.7) 65.8  (15.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 96 participants 196 participants
Female
36
  36.0%
39
  40.6%
75
  38.3%
Male
64
  64.0%
57
  59.4%
121
  61.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 96 participants 196 participants
France 87 84 171
Germany 13 12 25
Origin of sepsis   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 96 participants 196 participants
Lungs 53 58 111
Abdomen 24 18 42
Urogenital 8 14 22
Skin, bone and soft tissue 6 4 10
Other 5 2 7
Unknown 4 2 6
Neurological system 3 2 5
Ears-nose-throat system 2 0 2
[1]
Measure Description: Multiple origins of sepsis could be reported for a single patient.
1.Primary Outcome
Title Amount of Study Drug Required to Achieve Initial Hemodynamic Stabilization
Hide Description 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.
Time Frame until hemodynamic stabilization (up to 48 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization.
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 88 86
Mean (Standard Deviation)
Unit of Measure: Milliliter
1379  (886) 1709  (1164)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voluven® Arm, NaCl 0.9 % Arm
Comments

Null-hypothesis: The amount of study drug required to achieve initial hemodynamic stabilization in patients treated with Voluven® is higher than or equal to this amount in patients treated with NaCl.

Alternative hypothesis: The amount of study drug required to achieve initial hemodynamic stabilization is lower in patients treated with Voluven® than in patients treated with NaCl.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0185
Comments One-sided t-test assuming unequal variances (as variances were significantly different between treatment groups).No multiple comparisons were made. A priori threshold for statistical significance for the confirmatory analysis on FAS: 0.025 one-sided.
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -331
Confidence Interval (2-Sided) 95%
-640 to -21
Parameter Dispersion
Type: Standard Deviation
Value: 1033
Estimation Comments Considered difference: Voluven® minus NaCl 0.9 %
2.Secondary Outcome
Title Time From Start of Fluid Resuscitation With Study Drug to the Initial Hemodynamic Stabilization
Hide Description Time from start of fluid resuscitation with study drug to the initial hemodynamic stabilization
Time Frame until hemodynamic stabilization (up to 48 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 88 86
Mean (Standard Deviation)
Unit of Measure: Hours
11.8  (10.1) 14.3  (11.1)
3.Secondary Outcome
Title Quantity of Study Drug in 4 Days
Hide Description Total quantity of study drug infused over four consecutive days in the ICU
Time Frame 4 days
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 88 86
Mean (Standard Deviation)
Unit of Measure: Milliliter
2615  (1499) 2788  (1799)
4.Secondary Outcome
Title Time From Start of Study Drug to Start of Enteral Nutrition in the Subgroup of Patients Who Received Enteral Nutrition
Hide Description Time from start of fluid resuscitation with study drug to start of enteral nutrition.
Time Frame Until start of enteral nutrition (up to 48 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 62 67
Mean (Standard Deviation)
Unit of Measure: Hours
24.6  (32.7) 26.9  (33.8)
5.Secondary Outcome
Title Time From Start of Fluid Resuscitation With Study Drug to Start of Enteral Nutrition After Hemodynamic Stabilization
Hide Description Administration of enteral nutrition before initial hemodynamic stabilization was ignored in this analysis.
Time Frame up to 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 62 67
Mean (Standard Deviation)
Unit of Measure: Hours
25.9  (32.1) 27.6  (33.6)
6.Secondary Outcome
Title Total Amount of Enteral Calories During the First Seven Days of Enteral Nutrition
Hide Description This amount will be calculated from start of enteral nutrition until 7 am of day 8
Time Frame 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 62 67
Mean (Standard Deviation)
Unit of Measure: kcal
6877  (5008) 7429  (4381)
7.Secondary Outcome
Title Length of Stay in the Intensive Care Unit (ICU)
Hide Description 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).
Time Frame Until discharge from ICU (up to day 90)
Hide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization.

Calculated for patients who did not die before end of study of the individual patient

Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 58 61
Mean (Standard Deviation)
Unit of Measure: Days
15.4  (11.1) 20.2  (22.2)
8.Secondary Outcome
Title Length of Stay in the ICU
Hide Description 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).
Time Frame Until discharge from ICU (up to Day 90)
Hide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization.

Imputed with the longest possible duration for patients who died before end of the study of the individual patient.

Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 88 86
Mean (Standard Deviation)
Unit of Measure: Days
40.0  (36.5) 39.6  (36.3)
9.Secondary Outcome
Title Length of Stay in the Hospital
Hide Description 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).
Time Frame Until discharge from hospital (up to day 90)
Hide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization.

Calculated for patients who did not die before end of study of the individual patient.

Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 58 61
Mean (Standard Deviation)
Unit of Measure: Days
37.7  (26.5) 42.7  (31.6)
10.Secondary Outcome
Title Length of Stay in the Hospital
Hide Description 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).
Time Frame Until discharge from hospital (up to Day 90)
Hide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization.

Imputed with the longest possible duration for patients who died before end of the study of the individual patient.

Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 88 86
Mean (Standard Deviation)
Unit of Measure: Days
56.1  (33.5) 56.9  (34.7)
11.Secondary Outcome
Title Area Under the Curve (AUC) of Sepsis-related Organ Failure Assessment (SOFA) Score Per Day From Screening to Day 4
Hide Description

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).

Time Frame From Screening to Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) = all randomized patients treated with study drug who reached hemodynamic stabilization
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 82 74
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
6.9  (3.3) 7.6  (3.1)
12.Other Pre-specified Outcome
Title Mortality
Hide Description Mortality was reported for the time period from Screening until the end of follow-up.
Time Frame From Screening to end of Follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population (TRT) = all randomized patients treated with study drug. Two patients in the Voluven® arm died due to non-treatment emergent SAEs.
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4 Voluven® 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.
NaCl 0.9 % 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
Overall Number of Participants Analyzed 100 96
Measure Type: Number
Unit of Measure: Participants
From screening until (and including) Day 28 31 24
From screening until end of follow-up 40 32
13.Other Pre-specified Outcome
Title Changes in Renal Function: 1. Acute Renal Failure (ARF) at Any Time After Screening
Hide Description Acute Renal Failure (ARF) was defined as a two fold increase in serum concentration over the value at screening at any time after screening.
Time Frame From screening to end of follow-up (up to day 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population (TRT) = all randomized patients treated with study drug. Patients without ARF were excluded from analysis if they had no creatinine value at Screening or no post-screening creatinine value.
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 98 95
Measure Type: Number
Unit of Measure: Participants
24 19
14.Other Pre-specified Outcome
Title Changes in Renal Function: 2. Acute Kidney Injury Network (AKIN) Classification
Hide Description Acute Kidney Injury Network (AKIN) Classification in this study is based on serum creatinine values and renal replacement therapy, i.e. ignoring criteria based on urine output, as fulfilment of urine output criteria cannot be determined from the data collected in the study. AKIN ranges from stage 1 to stage 3 (worst outcome). Stages differ in serum creatinine increase. Stage 1: Increase ≥ 0.3mg/dL or ≥ 150%-200% from reference; Stage 2: Increase ≥ 200%-300% from reference; Stage 3: Increase >300% from reference with an acute increase of at least 0.5mg/dL or renal replacement therapy.
Time Frame From screening to end of follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population (TRT) = all randomized patients treated with study drug
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 100 96
Measure Type: Number
Unit of Measure: Participants
None 52 52
AKIN Stage 1 21 21
AKIN Stage 2 5 6
AKIN Stage 3 22 17
15.Other Pre-specified Outcome
Title Changes in Renal Function: 3. Risk, Injury, Failure, Loss, End-stage Kidney Disease (RIFLE) Classification
Hide Description

Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) Classification in this study is based on serum creatinine values and renal replacement therapy, i.e. ignoring criteria based on urine output, as fulfilment of urine output criteria cannot be determined from the data collected in the study.

RIFLE comprises five categories: Risk (R), Injury (I), Failure (F), Loss (L), End-stage kidney disease (E) (worst outcome). R, I and F are based on increase in serum creatinine. L and E are based on administration of renal replacement therapy.

Time Frame From screening to end of follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population (TRT) = all randomized patients treated with study drug
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description:
6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day
NaCl 0.9 %; 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
Overall Number of Participants Analyzed 100 96
Measure Type: Number
Unit of Measure: Participants
None 77 73
Risk 13 11
Injury 4 5
Failure 5 7
Loss 1 0
End-stage kidney disease 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description Regular assessment by Pharmacovigilance and Safety Assessor
 
Arm/Group Title Voluven® Arm NaCl 0.9 % Arm
Hide Arm/Group Description 6 % Hydroxyethylstarch 130/0.4; Voluven® rates were not to exceed 50 mL/kg/day on the first days and 25 mL/kg/day from the second to the fourth day NaCl 0.9 %; 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
All-Cause Mortality
Voluven® Arm NaCl 0.9 % Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Voluven® Arm NaCl 0.9 % Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   53/100 (53.00%)   44/96 (45.83%) 
Blood and lymphatic system disorders     
Anaemia  1  0/100 (0.00%)  1/96 (1.04%) 
Cardiac disorders     
Acute right ventricular failure  1  0/100 (0.00%)  1/96 (1.04%) 
Bradyarrhythmia  1  1/100 (1.00%)  0/96 (0.00%) 
Cardiac arrest  1  5/100 (5.00%)  6/96 (6.25%) 
Cardiac tamponade  1  0/100 (0.00%)  1/96 (1.04%) 
Pericardial haemorrhage  1  0/100 (0.00%)  1/96 (1.04%) 
Supraventricular tachycardia  1  1/100 (1.00%)  0/96 (0.00%) 
Gastrointestinal disorders     
Colitis ischaemic  1  0/100 (0.00%)  1/96 (1.04%) 
Duodenal perforation  1  1/100 (1.00%)  0/96 (0.00%) 
Intestinal ischaemia  1  1/100 (1.00%)  0/96 (0.00%) 
Intestinal obstruction  1  0/100 (0.00%)  1/96 (1.04%) 
Peritonitis  1  1/100 (1.00%)  1/96 (1.04%) 
General disorders     
Condition aggravated  1  4/100 (4.00%)  0/96 (0.00%) 
Multi-organ failure  1  7/100 (7.00%)  5/96 (5.21%) 
Oedema due to cardiac disease  1  0/100 (0.00%)  1/96 (1.04%) 
Sudden death  1  1/100 (1.00%)  0/96 (0.00%) 
Infections and infestations     
Abdominal sepsis  1  0/100 (0.00%)  1/96 (1.04%) 
Pneumonia  1  4/100 (4.00%)  3/96 (3.13%) 
Pseudomembranous colitis  1  0/100 (0.00%)  1/96 (1.04%) 
Sepsis  1  1/100 (1.00%)  3/96 (3.13%) 
Septic shock  1  9/100 (9.00%)  8/96 (8.33%) 
Injury, poisoning and procedural complications     
Haemodilution  1  8/100 (8.00%)  9/96 (9.38%) 
Tracheal haemorrhage  1  1/100 (1.00%)  0/96 (0.00%) 
Investigations     
Blood chloride increased  1  0/100 (0.00%)  1/96 (1.04%) 
Venous oxygen saturation decreased  1  0/100 (0.00%)  1/96 (1.04%) 
Metabolism and nutrition disorders     
Hyperchloraemia  1  0/100 (0.00%)  1/96 (1.04%) 
Hypernatraemia  1  0/100 (0.00%)  1/96 (1.04%) 
Hypokalaemia  1  0/100 (0.00%)  1/96 (1.04%) 
Hypoproteinaemia  1  1/100 (1.00%)  0/96 (0.00%) 
Lactic acidosis  1  0/100 (0.00%)  1/96 (1.04%) 
Marasmus  1  0/100 (0.00%)  1/96 (1.04%) 
Tumour lysis syndrome  1  0/100 (0.00%)  1/96 (1.04%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bronchial carcinoma  1  1/100 (1.00%)  0/96 (0.00%) 
Pleural carcinoma  1  0/100 (0.00%)  1/96 (1.04%) 
Tonsil cancer  1  0/100 (0.00%)  1/96 (1.04%) 
Nervous system disorders     
Cerebral disorder  1  1/100 (1.00%)  0/96 (0.00%) 
Cerebrovascular accident  1  1/100 (1.00%)  0/96 (0.00%) 
Coma  1  1/100 (1.00%)  1/96 (1.04%) 
Haemorrhage intracranial  1  0/100 (0.00%)  1/96 (1.04%) 
Renal and urinary disorders     
Renal failure  1  3/100 (3.00%)  3/96 (3.13%) 
Renal failure acute  1  3/100 (3.00%)  2/96 (2.08%) 
Renal impairment  1  0/100 (0.00%)  2/96 (2.08%) 
Reproductive system and breast disorders     
Acute pulmonary oedema  1  2/100 (2.00%)  0/96 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  2/100 (2.00%)  1/96 (1.04%) 
Acute respiratory failure  1  1/100 (1.00%)  2/96 (2.08%) 
Hypoxia  1  2/100 (2.00%)  0/96 (0.00%) 
Lung disorder  1  1/100 (1.00%)  0/96 (0.00%) 
Pneumothorax  1  2/100 (2.00%)  1/96 (1.04%) 
Pulmonary embolism  1  1/100 (1.00%)  1/96 (1.04%) 
Respiratory distress  1  0/100 (0.00%)  2/96 (2.08%) 
Respiratory failure  1  2/100 (2.00%)  0/96 (0.00%) 
Respiratory fatigue  1  1/100 (1.00%)  0/96 (0.00%) 
Skin and subcutaneous tissue disorders     
Toxic epidermal necrolysis  1  1/100 (1.00%)  0/96 (0.00%) 
Surgical and medical procedures     
Withdrawal of life support  1  0/100 (0.00%)  1/96 (1.04%) 
Vascular disorders     
Hypotension  1  2/100 (2.00%)  0/96 (0.00%) 
Peripheral ischaemia  1  0/100 (0.00%)  1/96 (1.04%) 
Shock  1  2/100 (2.00%)  1/96 (1.04%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 13.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Voluven® Arm NaCl 0.9 % Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   99/100 (99.00%)   95/96 (98.96%) 
Blood and lymphatic system disorders     
Anaemia  1  22/100 (22.00%)  21/96 (21.88%) 
Anaemia of chronic disease  1  1/100 (1.00%)  0/96 (0.00%) 
Coagulopathy  1  1/100 (1.00%)  0/96 (0.00%) 
Disseminated intravascular coagulation  1  3/100 (3.00%)  4/96 (4.17%) 
Hypocoagulable state  1  1/100 (1.00%)  0/96 (0.00%) 
Leukocytosis  1  1/100 (1.00%)  0/96 (0.00%) 
Leukopenia  1  1/100 (1.00%)  4/96 (4.17%) 
Thrombocytopenia  1  6/100 (6.00%)  6/96 (6.25%) 
Thrombocytosis  1  1/100 (1.00%)  0/96 (0.00%) 
Cardiac disorders     
Arrhythmia  1  6/100 (6.00%)  0/96 (0.00%) 
Atrial fibrillation  1  1/100 (1.00%)  2/96 (2.08%) 
Atrial flutter  1  0/100 (0.00%)  1/96 (1.04%) 
Bradycardia  1  2/100 (2.00%)  3/96 (3.13%) 
Cardiac arrest  1  1/100 (1.00%)  0/96 (0.00%) 
Cardiac failure  1  2/100 (2.00%)  0/96 (0.00%) 
Cyanosis  1  0/100 (0.00%)  1/96 (1.04%) 
Low cardiac output syndrome  1  1/100 (1.00%)  0/96 (0.00%) 
Sinus tachycardia  1  0/100 (0.00%)  1/96 (1.04%) 
Supraventricular tachycardia  1  1/100 (1.00%)  0/96 (0.00%) 
Tachyarrhythmia  1  3/100 (3.00%)  2/96 (2.08%) 
Tachycardia  1  9/100 (9.00%)  9/96 (9.38%) 
Ventricular arrhythmia  1  0/100 (0.00%)  1/96 (1.04%) 
Endocrine disorders     
Diabetes insipidus  1  1/100 (1.00%)  0/96 (0.00%) 
Eye disorders     
Pupils unequal  1  0/100 (0.00%)  1/96 (1.04%) 
Gastrointestinal disorders     
Abdominal distension  1  0/100 (0.00%)  3/96 (3.13%) 
Abdominal pain  1  7/100 (7.00%)  5/96 (5.21%) 
Ascites  1  0/100 (0.00%)  1/96 (1.04%) 
Constipation  1  9/100 (9.00%)  16/96 (16.67%) 
Diarrhoea  1  17/100 (17.00%)  22/96 (22.92%) 
Gastritis  1  0/100 (0.00%)  1/96 (1.04%) 
Gastrointestinal haemorrhage  1  1/100 (1.00%)  0/96 (0.00%) 
Gastrointestinal necrosis  1  1/100 (1.00%)  0/96 (0.00%) 
Gastrooesophageal reflux disease  1  2/100 (2.00%)  1/96 (1.04%) 
Ileus  1  0/100 (0.00%)  2/96 (2.08%) 
Impaired gastric emptying  1  0/100 (0.00%)  1/96 (1.04%) 
Intestinal perforation  1  1/100 (1.00%)  0/96 (0.00%) 
Malaena  1  0/100 (0.00%)  1/96 (1.04%) 
Nausea  1  1/100 (1.00%)  3/96 (3.13%) 
Rectal haemorrhage  1  1/100 (1.00%)  0/96 (0.00%) 
Regurgitation  1  1/100 (1.00%)  3/96 (3.13%) 
Vomiting  1  15/100 (15.00%)  17/96 (17.71%) 
General disorders     
Chest pain  1  1/100 (1.00%)  1/96 (1.04%) 
Device breakage  1  1/100 (1.00%)  0/96 (0.00%) 
Generalised oedema  1  0/100 (0.00%)  1/96 (1.04%) 
Oedema  1  3/100 (3.00%)  4/96 (4.17%) 
Oedema due to cardiac disease  1  1/100 (1.00%)  0/96 (0.00%) 
Oedema peripheral  1  3/100 (3.00%)  1/96 (1.04%) 
Pain  1  4/100 (4.00%)  4/96 (4.17%) 
Pyrexia  1  13/100 (13.00%)  3/96 (3.13%) 
Hepatobiliary disorders     
Cholangiolitis  1  0/100 (0.00%)  1/96 (1.04%) 
Cholestasis  1  1/100 (1.00%)  0/96 (0.00%) 
Cytolytic hepatitis  1  0/100 (0.00%)  1/96 (1.04%) 
Hyperbilirubinaemia  1  2/100 (2.00%)  2/96 (2.08%) 
Jaundice cholestatic  1  1/100 (1.00%)  0/96 (0.00%) 
Infections and infestations     
Acute sinusitis  1  0/100 (0.00%)  1/96 (1.04%) 
Bronchitis  1  0/100 (0.00%)  1/96 (1.04%) 
Candidiasis  1  0/100 (0.00%)  1/96 (1.04%) 
Fungal skin infection  1  0/100 (0.00%)  2/96 (2.08%) 
Herpes simplex  1  0/100 (0.00%)  1/96 (1.04%) 
Infection  1  0/100 (0.00%)  1/96 (1.04%) 
Lung infection pseudomonal  1  2/100 (2.00%)  1/96 (1.04%) 
Oral herpes  1  1/100 (1.00%)  0/96 (0.00%) 
Peritoneal abscess  1  1/100 (1.00%)  0/96 (0.00%) 
Pneumonia  1  4/100 (4.00%)  3/96 (3.13%) 
Pneumonia pneumococcal  1  0/100 (0.00%)  1/96 (1.04%) 
Post procedural infection  1  0/100 (0.00%)  1/96 (1.04%) 
Septic shock  1  0/100 (0.00%)  1/96 (1.04%) 
Tuberculosis  1  1/100 (1.00%)  0/96 (0.00%) 
Injury, poisoning and procedural complications     
Airway complication of anaesthesia  1  0/100 (0.00%)  1/96 (1.04%) 
Failure to anastomose  1  0/100 (0.00%)  1/96 (1.04%) 
Femur fracture  1  0/100 (0.00%)  1/96 (1.04%) 
Haemodilution  1  9/100 (9.00%)  10/96 (10.42%) 
Mechanical ventilation complication  1  1/100 (1.00%)  1/96 (1.04%) 
Open wound  1  0/100 (0.00%)  1/96 (1.04%) 
Post procedural haemorrhage  1  0/100 (0.00%)  1/96 (1.04%) 
Investigations     
Activated partial thromboplastin time prolonged  1  1/100 (1.00%)  0/96 (0.00%) 
Aspiration bronchial  1  1/100 (1.00%)  0/96 (0.00%) 
Blood bicarbonate decreased  1  0/100 (0.00%)  1/96 (1.04%) 
Blood bicarbonate increased  1  1/100 (1.00%)  0/96 (0.00%) 
Blood creatine increased  1  1/100 (1.00%)  1/96 (1.04%) 
Blood creatinine increased  1  2/100 (2.00%)  0/96 (0.00%) 
Blood potassium decreased  1  1/100 (1.00%)  0/96 (0.00%) 
Blood pressure diastolic increased  1  0/100 (0.00%)  1/96 (1.04%) 
Blood pressure systolic increased  1  0/100 (0.00%)  1/96 (1.04%) 
Blood urea increased  1  3/100 (3.00%)  2/96 (2.08%) 
Central venous pressure decreased  1  2/100 (2.00%)  1/96 (1.04%) 
Coagulation test abnormal  1  1/100 (1.00%)  0/96 (0.00%) 
Haemoglobin decreased  1  1/100 (1.00%)  0/96 (0.00%) 
Mean arterial pressure decreased  1  0/100 (0.00%)  1/96 (1.04%) 
Oxygen saturation decreased  1  0/100 (0.00%)  2/96 (2.08%) 
PO2 decreased  1  2/100 (2.00%)  0/96 (0.00%) 
PO2 increased  1  0/100 (0.00%)  1/96 (1.04%) 
Red blood cell count decreased  1  1/100 (1.00%)  0/96 (0.00%) 
Urine output decreased  1  19/100 (19.00%)  15/96 (15.63%) 
Venous oxygen saturation decreased  1  6/100 (6.00%)  12/96 (12.50%) 
Weight increased  1  0/100 (0.00%)  1/96 (1.04%) 
Metabolism and nutrition disorders     
Acidosis  1  7/100 (7.00%)  13/96 (13.54%) 
Alkalosis  1  16/100 (16.00%)  14/96 (14.58%) 
Food intolerance  1  0/100 (0.00%)  1/96 (1.04%) 
Hyperchloraemia  1  23/100 (23.00%)  28/96 (29.17%) 
Hyperglycaemia  1  1/100 (1.00%)  3/96 (3.13%) 
Hyperkalaemia  1  7/100 (7.00%)  3/96 (3.13%) 
Hyperlactacidaemia  1  3/100 (3.00%)  1/96 (1.04%) 
Hypernatraemia  1  2/100 (2.00%)  4/96 (4.17%) 
Hyperproteinaemia  1  1/100 (1.00%)  0/96 (0.00%) 
Hyperuricaemia  1  2/100 (2.00%)  1/96 (1.04%) 
Hypervolaemia  1  0/100 (0.00%)  1/96 (1.04%) 
Hypoalbuminaemia  1  1/100 (1.00%)  0/96 (0.00%) 
Hypocalcaemia  1  3/100 (3.00%)  0/96 (0.00%) 
Hypoglycaemia  1  9/100 (9.00%)  12/96 (12.50%) 
Hypokalaemia  1  22/100 (22.00%)  29/96 (30.21%) 
Hyponatraemia  1  2/100 (2.00%)  4/96 (4.17%) 
Hypophosphataemia  1  1/100 (1.00%)  1/96 (1.04%) 
Hypoproteinaemia  1  29/100 (29.00%)  22/96 (22.92%) 
Hypovolaemia  1  3/100 (3.00%)  3/96 (3.13%) 
Lactic acidosis  1  1/100 (1.00%)  1/96 (1.04%) 
Metabolic acidosis  1  6/100 (6.00%)  1/96 (1.04%) 
Metabolic alkalosis  1  2/100 (2.00%)  0/96 (0.00%) 
Vitamin K deficiency  1  1/100 (1.00%)  0/96 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/100 (0.00%)  1/96 (1.04%) 
Musculoskeletal pain  1  1/100 (1.00%)  0/96 (0.00%) 
Rhabdomyolysis  1  0/100 (0.00%)  1/96 (1.04%) 
Nervous system disorders     
Brain injury  1  1/100 (1.00%)  0/96 (0.00%) 
Convulsion  1  1/100 (1.00%)  3/96 (3.13%) 
Critical illness polyneuropathy  1  0/100 (0.00%)  1/96 (1.04%) 
Headache  1  1/100 (1.00%)  2/96 (2.08%) 
Myoclonus  1  1/100 (1.00%)  0/96 (0.00%) 
Neuropathy peripheral  1  1/100 (1.00%)  0/96 (0.00%) 
Psychiatric disorders     
Agitation  1  3/100 (3.00%)  12/96 (12.50%) 
Anxiety  1  1/100 (1.00%)  3/96 (3.13%) 
Confusional state  1  3/100 (3.00%)  1/96 (1.04%) 
Delirium  1  2/100 (2.00%)  1/96 (1.04%) 
Depression  1  1/100 (1.00%)  0/96 (0.00%) 
Hallucination  1  1/100 (1.00%)  0/96 (0.00%) 
Renal and urinary disorders     
Azotaemia  1  1/100 (1.00%)  1/96 (1.04%) 
Haematuria  1  4/100 (4.00%)  0/96 (0.00%) 
Oliguria  1  4/100 (4.00%)  5/96 (5.21%) 
Renal failure  1  8/100 (8.00%)  6/96 (6.25%) 
Renal failure acute  1  7/100 (7.00%)  0/96 (0.00%) 
Renal failure chronic  1  0/100 (0.00%)  1/96 (1.04%) 
Renal impairment  1  2/100 (2.00%)  0/96 (0.00%) 
Urinary retention  1  0/100 (0.00%)  1/96 (1.04%) 
Reproductive system and breast disorders     
Vaginal haemorrhage  1  0/100 (0.00%)  1/96 (1.04%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  1/100 (1.00%)  2/96 (2.08%) 
Acute respiratory distress syndrome  1  3/100 (3.00%)  0/96 (0.00%) 
Aspiration  1  4/100 (4.00%)  0/96 (0.00%) 
Atelectasis  1  0/100 (0.00%)  1/96 (1.04%) 
Bronchial obstruction  1  1/100 (1.00%)  0/96 (0.00%) 
Bronchospasm  1  1/100 (1.00%)  0/96 (0.00%) 
Dyspnoea  1  1/100 (1.00%)  0/96 (0.00%) 
Hypercapnia  1  4/100 (4.00%)  3/96 (3.13%) 
Hyperventilation  1  0/100 (0.00%)  1/96 (1.04%) 
Hypocapnia  1  0/100 (0.00%)  1/96 (1.04%) 
Hypoxia  1  33/100 (33.00%)  35/96 (36.46%) 
Lung disorder  1  1/100 (1.00%)  0/96 (0.00%) 
Pleural effusion  1  1/100 (1.00%)  2/96 (2.08%) 
Pleurisy  1  1/100 (1.00%)  0/96 (0.00%) 
Pneumothorax  1  1/100 (1.00%)  1/96 (1.04%) 
Pulmonary embolism  1  1/100 (1.00%)  0/96 (0.00%) 
Pulmonary oedema  1  1/100 (1.00%)  1/96 (1.04%) 
Respiratory acidosis  1  6/100 (6.00%)  4/96 (4.17%) 
Respiratory alkalosis  1  6/100 (6.00%)  6/96 (6.25%) 
Respiratory failure  1  2/100 (2.00%)  3/96 (3.13%) 
Skin and subcutaneous tissue disorders     
Decubitus ulcer  1  0/100 (0.00%)  1/96 (1.04%) 
Erythema  1  2/100 (2.00%)  0/96 (0.00%) 
Livedo reticularis  1  0/100 (0.00%)  1/96 (1.04%) 
Pruritus  1  0/100 (0.00%)  1/96 (1.04%) 
Rash  1  1/100 (1.00%)  1/96 (1.04%) 
Rash erythematous  1  0/100 (0.00%)  1/96 (1.04%) 
Vascular disorders     
Haematoma  1  0/100 (0.00%)  1/96 (1.04%) 
Hypertension  1  9/100 (9.00%)  8/96 (8.33%) 
Hypotension  1  35/100 (35.00%)  38/96 (39.58%) 
Labile hypertension  1  0/100 (0.00%)  1/96 (1.04%) 
Peripheral ischaemia  1  0/100 (0.00%)  1/96 (1.04%) 
Venous thrombosis  1  1/100 (1.00%)  0/96 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 13.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
All investigators agreed that there will be one or more publications describing the study and the results. No center or combination of centers will submit their results for publication separately. Highest recruiting centers and Fresenius Kabi will contribute authors. The writing of the manuscript will be a collaborative effort.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Professor Dr. Martin Westphal
Organization: Fresenius Kabi Aktiengesellschaft
Phone: +49 6172 686 ext 7280
EMail: martin.westphal@fresenius-kabi.com
Layout table for additonal information
Responsible Party: Fresenius Kabi
ClinicalTrials.gov Identifier: NCT00464204    
Other Study ID Numbers: 06-HE06-01
2006-004350-25 ( EudraCT Number )
First Submitted: April 20, 2007
First Posted: April 23, 2007
Results First Submitted: May 30, 2011
Results First Posted: August 2, 2011
Last Update Posted: January 11, 2012