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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Fresenius Kabi
ClinicalTrials.gov Identifier:
NCT00464204
First received: April 20, 2007
Last updated: January 9, 2012
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Sepsis
Drug: 6 % Hydroxyethylstarch 130/0.4 = "Voluven®"
Drug: 0.9 % NaCl
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Voluven on Hemodynamics and Tolerability of Enteral Nutrition in Patients With Severe Sepsis

Resource links provided by NLM:


Further study details as provided by Fresenius Kabi:

Primary Outcome Measures:
  • Amount of Study Drug Required to Achieve Initial Hemodynamic Stabilization [ Time Frame: until hemodynamic stabilization (up to 48 hours) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time From Start of Fluid Resuscitation With Study Drug to the Initial Hemodynamic Stabilization [ Time Frame: until hemodynamic stabilization (up to 48 hours) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 Hospital [ Time Frame: Until discharge from hospital (up to Day 90) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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).



Enrollment: 196
Study Start Date: July 2007
Study Completion Date: December 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Voluven® Arm 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®
Active Comparator: 0.9 % NaCl 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00464204

Locations
France
Hôpital Sud, Unité de Réanimation Médicale
Amiens, France, 80054
Centre Hospitalier d'Avignon, Service de Réanimation Polyvalente
Avignon, France, 84902
Centre Hospitalier de Belfort-Montbéliard, Service de Réanimation et Maladies Infectieuses, Site de Belfort
Belfort, France, 90000
CHU de Bicêtre, Dpt d'Anesthésie Réanimation Chir.
Bicêtre, France, 94270
Hôpital Avicenne, Service de Réanimation
Bobigny, France, 93009
Centre Hospitalier Fleyriat, Service de Réanimation Polyvalente
Bourg-en-Bresse, France, 01012
CH Manchester, Service de Réanimation Polyvalente
Charleville-Mézières, France, 08011
CH Sud Francilien, Site Gilles de Corbeil, Réanimation Polyvalente
Corbeil-Essonnes, France, 91106
CHU de Dijon - Hôpital du Bocage Service de Réanimation Médicale
Dijon, France, 21079
CH Meaux, Service de Réanimation
Meaux, France, 77104
Centre Hospitalier de Metz, Réa Polyvalente
Metz, France, 57038
Hôpital Lapeyronie / CHU Montpellier, Département d'Anesthésie Réanimation
Montpellier, France, 34090
Hôpital Central, Service Anesthésie-Réanimation, Chirurgicale CHU
Nancy, France, 54035
CHU Nîmes, Service de Réanimation, Division Anesthésie-Réa Douleur Urgence, Groupe Hospitalo-Universitaire Caremeau,
Nîmes, France, 30029
Hôpital de la Source, Réanimation Polyvalente
Orléans, France, 45032
Hôpital St Antoine, Réanimation Médicale
Paris, France, 7551
Hôpital St Louis, Département Anesthésie et Réanimation Chirurgicale
Paris, France, 75010
Hôpital Saint-Joseph, Service de Réanimation Polyvalente
Paris, France, 75014
CH Roanne, Service de Réanimation
Roanne, France, 42328
CHI Poissy - St Germain en Laye, Site de St Germain en Laye
St. Germain en Laye, France, 78100
Hôpital Civil de Strasbourg, Service de Réanimation Médicale
Strasbourg, France, 67091
Germany
Klinik und Poliklinik für Anästhesiologie und Intensivtherapie - Universitätsklinikum Leipzig AöR
Leipzig, Germany, 04103
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin der Westf. Wilhelms-Universität
Münster, Germany, 48149
Universitätsklinikum Tübingen, Klinik für Anästhesiologie und Intensivmedizin
Tübingen, Germany, 72076
Sponsors and Collaborators
Fresenius Kabi
Investigators
Study Chair: Bertrand Guidet, Prof., MD Hôpital St Antoine, Réanimation Médicale
  More Information

No publications provided

Responsible Party: Fresenius Kabi
ClinicalTrials.gov Identifier: NCT00464204     History of Changes
Other Study ID Numbers: 06-HE06-01, 2006-004350-25
Study First Received: April 20, 2007
Results First Received: May 30, 2011
Last Updated: January 9, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Hetastarch
Plasma Substitutes
Blood Substitutes
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014