search
Back to results

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

Primary Purpose

Sepsis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
6 % Hydroxyethylstarch 130/0.4 = "Voluven®"
0.9 % NaCl
Sponsored by
Fresenius Kabi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sepsis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hôpital Sud, Unité de Réanimation Médicale
  • Centre Hospitalier d'Avignon, Service de Réanimation Polyvalente
  • Centre Hospitalier de Belfort-Montbéliard, Service de Réanimation et Maladies Infectieuses, Site de Belfort
  • CHU de Bicêtre, Dpt d'Anesthésie Réanimation Chir.
  • Hôpital Avicenne, Service de Réanimation
  • Centre Hospitalier Fleyriat, Service de Réanimation Polyvalente
  • CH Manchester, Service de Réanimation Polyvalente
  • CH Sud Francilien, Site Gilles de Corbeil, Réanimation Polyvalente
  • CHU de Dijon - Hôpital du Bocage Service de Réanimation Médicale
  • CH Meaux, Service de Réanimation
  • Centre Hospitalier de Metz, Réa Polyvalente
  • Hôpital Lapeyronie / CHU Montpellier, Département d'Anesthésie Réanimation
  • Hôpital Central, Service Anesthésie-Réanimation, Chirurgicale CHU
  • CHU Nîmes, Service de Réanimation, Division Anesthésie-Réa Douleur Urgence, Groupe Hospitalo-Universitaire Caremeau,
  • Hôpital de la Source, Réanimation Polyvalente
  • Hôpital St Louis, Département Anesthésie et Réanimation Chirurgicale
  • Hôpital Saint-Joseph, Service de Réanimation Polyvalente
  • Hôpital St Antoine, Réanimation Médicale
  • CH Roanne, Service de Réanimation
  • CHI Poissy - St Germain en Laye, Site de St Germain en Laye
  • Hôpital Civil de Strasbourg, Service de Réanimation Médicale
  • Klinik und Poliklinik für Anästhesiologie und Intensivtherapie - Universitätsklinikum Leipzig AöR
  • Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin der Westf. Wilhelms-Universität
  • Universitätsklinikum Tübingen, Klinik für Anästhesiologie und Intensivmedizin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Voluven® Arm

0.9 % NaCl

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
Quantity of Study Drug in 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 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
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
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)
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
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
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
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).

Full Information

First Posted
April 20, 2007
Last Updated
January 9, 2012
Sponsor
Fresenius Kabi
search

1. Study Identification

Unique Protocol Identification Number
NCT00464204
Brief Title
Effects of Voluven on Hemodynamics and Tolerability of Enteral Nutrition in Patients With Severe Sepsis
Acronym
CRYSTMAS
Official Title
Effects of Voluven on Hemodynamics and Tolerability of Enteral Nutrition in Patients With Severe Sepsis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fresenius Kabi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
196 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Voluven® Arm
Arm Type
Experimental
Arm Title
0.9 % NaCl
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
6 % Hydroxyethylstarch 130/0.4 = "Voluven®"
Other Intervention Name(s)
Voluven®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
0.9 % NaCl
Intervention Description
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.
Primary Outcome Measure Information:
Title
Amount of Study Drug Required to Achieve Initial Hemodynamic Stabilization
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)
Secondary Outcome Measure Information:
Title
Time From Start of Fluid Resuscitation With Study Drug to the Initial Hemodynamic Stabilization
Description
Time from start of fluid resuscitation with study drug to the initial hemodynamic stabilization
Time Frame
until hemodynamic stabilization (up to 48 hours)
Title
Quantity of Study Drug in 4 Days
Description
Total quantity of study drug infused over four consecutive days in the ICU
Time Frame
4 days
Title
Time From Start of Study Drug to Start of Enteral Nutrition in the Subgroup of Patients Who Received Enteral Nutrition
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)
Title
Time From Start of Fluid Resuscitation With Study Drug to Start of Enteral Nutrition After Hemodynamic Stabilization
Description
Administration of enteral nutrition before initial hemodynamic stabilization was ignored in this analysis.
Time Frame
up to 48 hours
Title
Total Amount of Enteral Calories During the First Seven Days of Enteral Nutrition
Description
This amount will be calculated from start of enteral nutrition until 7 am of day 8
Time Frame
7 days
Title
Length of Stay in the Intensive Care Unit (ICU)
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)
Title
Length of Stay in the ICU
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)
Title
Length of Stay in the Hospital
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)
Title
Area Under the Curve (AUC) of Sepsis-related Organ Failure Assessment (SOFA) Score Per Day From Screening to Day 4
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
Other Pre-specified Outcome Measures:
Title
Mortality
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
Title
Changes in Renal Function: 1. Acute Renal Failure (ARF) at Any Time After Screening
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)
Title
Changes in Renal Function: 2. Acute Kidney Injury Network (AKIN) Classification
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
Title
Changes in Renal Function: 3. Risk, Injury, Failure, Loss, End-stage Kidney Disease (RIFLE) Classification
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bertrand Guidet, Prof., MD
Organizational Affiliation
Hôpital St Antoine, Réanimation Médicale
Official's Role
Study Chair
Facility Information:
Facility Name
Hôpital Sud, Unité de Réanimation Médicale
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
Centre Hospitalier d'Avignon, Service de Réanimation Polyvalente
City
Avignon
ZIP/Postal Code
84902
Country
France
Facility Name
Centre Hospitalier de Belfort-Montbéliard, Service de Réanimation et Maladies Infectieuses, Site de Belfort
City
Belfort
ZIP/Postal Code
90000
Country
France
Facility Name
CHU de Bicêtre, Dpt d'Anesthésie Réanimation Chir.
City
Bicêtre
ZIP/Postal Code
94270
Country
France
Facility Name
Hôpital Avicenne, Service de Réanimation
City
Bobigny
ZIP/Postal Code
93009
Country
France
Facility Name
Centre Hospitalier Fleyriat, Service de Réanimation Polyvalente
City
Bourg-en-Bresse
ZIP/Postal Code
01012
Country
France
Facility Name
CH Manchester, Service de Réanimation Polyvalente
City
Charleville-Mézières
ZIP/Postal Code
08011
Country
France
Facility Name
CH Sud Francilien, Site Gilles de Corbeil, Réanimation Polyvalente
City
Corbeil-Essonnes
ZIP/Postal Code
91106
Country
France
Facility Name
CHU de Dijon - Hôpital du Bocage Service de Réanimation Médicale
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
CH Meaux, Service de Réanimation
City
Meaux
ZIP/Postal Code
77104
Country
France
Facility Name
Centre Hospitalier de Metz, Réa Polyvalente
City
Metz
ZIP/Postal Code
57038
Country
France
Facility Name
Hôpital Lapeyronie / CHU Montpellier, Département d'Anesthésie Réanimation
City
Montpellier
ZIP/Postal Code
34090
Country
France
Facility Name
Hôpital Central, Service Anesthésie-Réanimation, Chirurgicale CHU
City
Nancy
ZIP/Postal Code
54035
Country
France
Facility Name
CHU Nîmes, Service de Réanimation, Division Anesthésie-Réa Douleur Urgence, Groupe Hospitalo-Universitaire Caremeau,
City
Nîmes
ZIP/Postal Code
30029
Country
France
Facility Name
Hôpital de la Source, Réanimation Polyvalente
City
Orléans
ZIP/Postal Code
45032
Country
France
Facility Name
Hôpital St Louis, Département Anesthésie et Réanimation Chirurgicale
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hôpital Saint-Joseph, Service de Réanimation Polyvalente
City
Paris
ZIP/Postal Code
75014
Country
France
Facility Name
Hôpital St Antoine, Réanimation Médicale
City
Paris
ZIP/Postal Code
7551
Country
France
Facility Name
CH Roanne, Service de Réanimation
City
Roanne
ZIP/Postal Code
42328
Country
France
Facility Name
CHI Poissy - St Germain en Laye, Site de St Germain en Laye
City
St. Germain en Laye
ZIP/Postal Code
78100
Country
France
Facility Name
Hôpital Civil de Strasbourg, Service de Réanimation Médicale
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Klinik und Poliklinik für Anästhesiologie und Intensivtherapie - Universitätsklinikum Leipzig AöR
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin der Westf. Wilhelms-Universität
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Universitätsklinikum Tübingen, Klinik für Anästhesiologie und Intensivmedizin
City
Tübingen
ZIP/Postal Code
72076
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
22624531
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs