Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

Tracking Information
First Submitted Date  ICMJE April 20, 2007
First Posted Date  ICMJE April 23, 2007
Results First Submitted Date  ICMJE May 30, 2011
Results First Posted Date  ICMJE August 2, 2011
Last Update Posted Date January 11, 2012
Study Start Date  ICMJE July 2007
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 4, 2011)
Amount of Study Drug Required to Achieve Initial Hemodynamic Stabilization [ Time Frame: until hemodynamic stabilization (up to 48 hours) ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 20, 2007)
  • Amount of Study Drug Required to Achieve Initial Hemodynamic Stabilization
  • Amount of enteral calories during 7 days after hemodynamic stabilization
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 4, 2011)
  • Time From Start of Fluid Resuscitation With Study Drug to the Initial Hemodynamic Stabilization [ Time Frame: until hemodynamic stabilization (up to 48 hours) ]
    Time from start of fluid resuscitation with study drug to the initial hemodynamic stabilization
  • Quantity of Study Drug in 4 Days [ Time Frame: 4 days ]
    Total quantity of study drug infused over four consecutive days in the ICU
  • Time From Start of Study Drug to Start of Enteral Nutrition in the Subgroup of Patients Who Received Enteral Nutrition [ Time Frame: Until start of enteral nutrition (up to 48 hours) ]
    Time from start of fluid resuscitation with study drug to start of enteral nutrition.
  • Time From Start of Fluid Resuscitation With Study Drug to Start of Enteral Nutrition After Hemodynamic Stabilization [ Time Frame: up to 48 hours ]
    Administration of enteral nutrition before initial hemodynamic stabilization was ignored in this analysis.
  • Total Amount of Enteral Calories During the First Seven Days of Enteral Nutrition [ Time Frame: 7 days ]
    This amount will be calculated from start of enteral nutrition until 7 am of day 8
  • Length of Stay in the Intensive Care Unit (ICU) [ Time Frame: Until discharge from ICU (up to day 90) ]
    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).
  • Length of Stay in the ICU [ Time Frame: Until discharge from ICU (up to Day 90) ]
    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).
  • Length of Stay in the Hospital [ Time Frame: Until discharge from hospital (up to day 90) ]
    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).
  • Area Under the Curve (AUC) of Sepsis-related Organ Failure Assessment (SOFA) Score Per Day From Screening to Day 4 [ Time Frame: 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2007)
  • Time from start of fluid resuscitation with study drug to hemodynamic stabilization
  • Quantity of Study Drug in 4 Days
  • Time from start of study drug to start of enteral nutrition
  • Length of stay in hospital and ICU
  • SOFA score
Current Other Pre-specified Outcome Measures
 (submitted: August 8, 2011)
  • Mortality [ Time Frame: From Screening to end of Follow-up ]
    Mortality was reported for the time period from Screening until the end of follow-up.
  • Changes in Renal Function: 1. Acute Renal Failure (ARF) at Any Time After Screening [ Time Frame: From screening to end of follow-up (up to day 90) ]
    Acute Renal Failure (ARF) was defined as a two fold increase in serum concentration over the value at screening at any time after screening.
  • Changes in Renal Function: 2. Acute Kidney Injury Network (AKIN) Classification [ Time Frame: From screening to end of follow-up ]
    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.
  • Changes in Renal Function: 3. Risk, Injury, Failure, Loss, End-stage Kidney Disease (RIFLE) Classification [ Time Frame: From screening to end of follow-up ]
    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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Voluven on Hemodynamics and Tolerability of Enteral Nutrition in Patients With Severe Sepsis
Official Title  ICMJE Effects of Voluven on Hemodynamics and Tolerability of Enteral Nutrition in Patients With Severe Sepsis
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Sepsis
Intervention  ICMJE
  • Drug: 6 % Hydroxyethylstarch 130/0.4 = "Voluven®"
    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.
    Other Name: Voluven®
  • Drug: 0.9 % NaCl
    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.
Study Arms  ICMJE
  • Experimental: Voluven® Arm
    Intervention: Drug: 6 % Hydroxyethylstarch 130/0.4 = "Voluven®"
  • Active Comparator: 0.9 % NaCl
    Intervention: Drug: 0.9 % NaCl
Publications * Guidet B, Martinet O, Boulain T, Philippart F, Poussel JF, Maizel J, Forceville X, Feissel M, Hasselmann M, Heininger A, Van Aken H. Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: the CRYSTMAS study. Crit Care. 2012 May 24;16(3):R94. doi: 10.1186/cc11358.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 4, 2011)
196
Original Enrollment  ICMJE
 (submitted: April 20, 2007)
180
Actual Study Completion Date  ICMJE December 2010
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00464204
Other Study ID Numbers  ICMJE 06-HE06-01
2006-004350-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fresenius Kabi
Study Sponsor  ICMJE Fresenius Kabi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Bertrand Guidet, Prof., MD Hôpital St Antoine, Réanimation Médicale
PRS Account Fresenius Kabi
Verification Date August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP