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

History of Changes

Results First Received: May 30, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Sepsis
Interventions:	Drug: 6 % Hydroxyethylstarch 130/0.4 = "Voluven®" Drug: 0.9 % NaCl

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were screened in intensive care units of the participating study sites in France and Germany.

Reporting Groups

	Description
Voluven® Arm	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 % Arm	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

Participant Flow: Overall Study

	Voluven® Arm	NaCl 0.9 % Arm
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.

Baseline Characteristics

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Reporting Groups

	Description
Voluven® Arm	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 % Arm	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	Total of all reporting groups

Baseline Measures

	Voluven® Arm	NaCl 0.9 % Arm	Total
Number of Participants [units: participants]	100	96	196
Age [units: years] Mean ± Standard Deviation	65.8 ± 15.4	65.9 ± 14.7	65.8 ± 15.0
Gender [units: participants]
Female	36	39	75
Male	64	57	121
Region of Enrollment [units: participants]
France	87	84	171
Germany	13	12	25
Origin of sepsis ^[1] [units: 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]	Multiple origins of sepsis could be reported for a single patient.

Outcome Measures

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1. Primary:

Amount of Study Drug Required to Achieve Initial Hemodynamic Stabilization [ Time Frame: until hemodynamic stabilization (up to 48 hours) ]

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2. Secondary:

Time From Start of Fluid Resuscitation With Study Drug to the Initial Hemodynamic Stabilization [ Time Frame: until hemodynamic stabilization (up to 48 hours) ]

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3. Secondary:

Quantity of Study Drug in 4 Days [ Time Frame: 4 days ]

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4. Secondary:

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) ]

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5. Secondary:

Time From Start of Fluid Resuscitation With Study Drug to Start of Enteral Nutrition After Hemodynamic Stabilization [ Time Frame: up to 48 hours ]

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6. Secondary:

Total Amount of Enteral Calories During the First Seven Days of Enteral Nutrition [ Time Frame: 7 days ]

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7. Secondary:

Length of Stay in the Intensive Care Unit (ICU) [ Time Frame: Until discharge from ICU (up to day 90) ]

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8. Secondary:

Length of Stay in the ICU [ Time Frame: Until discharge from ICU (up to Day 90) ]

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9. Secondary:

Length of Stay in the Hospital [ Time Frame: Until discharge from hospital (up to day 90) ]

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Measure Type	Secondary
Measure Title	Length of Stay in the Hospital
Measure 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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

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.

Reporting Groups

	Description
Voluven® Arm	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 % Arm	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

Measured Values

	Voluven® Arm	NaCl 0.9 % Arm
Number of Participants Analyzed [units: participants]	58	61
Length of Stay in the Hospital [units: Days] Mean ± Standard Deviation	37.7 ± 26.5	42.7 ± 31.6

No statistical analysis provided for Length of Stay in the Hospital

10. Secondary:

Length of Stay in the Hospital [ Time Frame: Until discharge from hospital (up to Day 90) ]

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11. Secondary:

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 ]

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12. Other Pre-specified:

Mortality [ Time Frame: From Screening to end of Follow-up ]

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13. Other Pre-specified:

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) ]

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14. Other Pre-specified:

Changes in Renal Function: 2. Acute Kidney Injury Network (AKIN) Classification [ Time Frame: From screening to end of follow-up ]

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15. Other Pre-specified:

Changes in Renal Function: 3. Risk, Injury, Failure, Loss, End-stage Kidney Disease (RIFLE) Classification [ Time Frame: From screening to end of follow-up ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Professor Dr. Martin Westphal
Organization: Fresenius Kabi Aktiengesellschaft
phone: +49 6172 686 ext 7280
e-mail: martin.westphal@fresenius-kabi.com

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

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