SepsisPhase 3CRYSTMASNCT00464204

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

A Phase 3 study testing 6 % Hydroxyethylstarch 130/0.4 = "Voluven®" and 0.9 % NaCl in people with Sepsis, run by Fresenius Kabi at 24 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Sepsis
What is being tested?: 6 % Hydroxyethylstarch 130/0.4 = "Voluven®" and 0.9 % NaCl
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 196 participants
Where: 24 sitesin 2 countries
Study dates: Jul 2007to Dec 2010
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Severe sepsis
Requirement for fluid resuscitation

Who cannot join

serum creatinine > 300µmol/L
Chronic renal failure
Anuria lasting more than 4 hours
Requirement for renal support

Trial locations and contacts

24 sites in 2 countries.

Country

City, postcode or hospital

24 sites in 2 countries

France21 sites

Hôpital Sud, Unité de Réanimation Médicale
Amiens, 80054
Centre Hospitalier d'Avignon, Service de Réanimation Polyvalente
Avignon, 84902
Centre Hospitalier de Belfort-Montbéliard, Service de Réanimation et Maladies Infectieuses, Site de Belfort
Belfort, 90000
CHU de Bicêtre, Dpt d'Anesthésie Réanimation Chir.
Bicêtre, 94270
Hôpital Avicenne, Service de Réanimation
Bobigny, 93009
Centre Hospitalier Fleyriat, Service de Réanimation Polyvalente
Bourg-en-Bresse, 01012
CH Manchester, Service de Réanimation Polyvalente
Charleville-Mézières, 08011
CH Sud Francilien, Site Gilles de Corbeil, Réanimation Polyvalente
Corbeil-Essonnes, 91106
CHU de Dijon - Hôpital du Bocage Service de Réanimation Médicale
Dijon, 21079
CH Meaux, Service de Réanimation
Meaux, 77104
Centre Hospitalier de Metz, Réa Polyvalente
Metz, 57038
Hôpital Lapeyronie / CHU Montpellier, Département d'Anesthésie Réanimation
Montpellier, 34090
Hôpital Central, Service Anesthésie-Réanimation, Chirurgicale CHU
Nancy, 54035
CHU Nîmes, Service de Réanimation, Division Anesthésie-Réa Douleur Urgence, Groupe Hospitalo-Universitaire Caremeau,
Nîmes, 30029
Hôpital de la Source, Réanimation Polyvalente
Orléans, 45032
Hôpital St Louis, Département Anesthésie et Réanimation Chirurgicale
Paris, 75010
Hôpital Saint-Joseph, Service de Réanimation Polyvalente
Paris, 75014
Hôpital St Antoine, Réanimation Médicale
Paris, 7551
CH Roanne, Service de Réanimation
Roanne, 42328
CHI Poissy - St Germain en Laye, Site de St Germain en Laye
Saint-Germain-en-Laye, 78100
Hôpital Civil de Strasbourg, Service de Réanimation Médicale
Strasbourg, 67091

Other trials in France

Germany3 sites

Klinik und Poliklinik für Anästhesiologie und Intensivtherapie - Universitätsklinikum Leipzig AöR
Leipzig, 04103
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin der Westf. Wilhelms-Universität
Münster, 48149
Universitätsklinikum Tübingen, Klinik für Anästhesiologie und Intensivmedizin
Tübingen, 72076

Other trials in Germany

About this study

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.

Conditions: Sepsis
Being tested: 6 % Hydroxyethylstarch 130/0.4 = "Voluven®", 0.9 % NaCl
Medical subject headings: Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

6 % Hydroxyethylstarch 130/0.4 = "Voluven®"Drug
Also called 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.
0.9 % NaClDrug
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 groups in NCT00464204
Study group	Role	What they receive
Voluven® Arm	Experimental	Not described Receives: Drug: 6 % Hydroxyethylstarch 130/0.4 = "Voluven®"
0.9 % NaCl	Active comparator	Not described Receives: Drug: 0.9 % NaCl

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: until hemodynamic stabilization (up to 48 hours)

Secondary outcomes (9)

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
Measured: until hemodynamic stabilization (up to 48 hours)
Quantity of Study Drug in 4 Days
Total quantity of study drug infused over four consecutive days in the ICU
Measured: 4 days
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.
Measured: Until start of enteral nutrition (up to 48 hours)
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.
Measured: up to 48 hours
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
Measured: 7 days
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).
Measured: Until discharge from ICU (up to day 90)
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).
Measured: Until discharge from ICU (up to Day 90)
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).
Measured: Until discharge from hospital (up to day 90)
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).
Measured: From Screening to Day 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2007Dec 2010

First posted23 Apr 2007 (estimated)
Study startJul 2007
Primary completionMay 2010
Study completionDec 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for SepsisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 196 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00464204
Sponsor's protocol ID: 06-HE06-01
Other IDs: 2006-004350-25
Acronym: CRYSTMAS
Status last verified: Aug 2011
First submitted: 20 Apr 2007
Last updated: 11 Jan 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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.
PubMed 22624531

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Sepsis trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Voluven on Hemodynamics and Tolerability of Enteral Nutrition in Patients With Severe Sepsis
ClinicalTrials.gov ID: NCT00464204
Acronym / sponsor ID: CRYSTMAS / 06-HE06-01
Conditions: Sepsis
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 196 participants (actual)
Lead sponsor: Fresenius KabiIndustry (pharma, biotech, devices)
Study start: Jul 2007
Primary completion: May 2010 (actual)
Study completion: Dec 2010 (actual)
First posted: 23 Apr 2007 (estimated)
Results: Posted 2 Aug 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Voluven® Arm	Experimental	Drug: 6 % Hydroxyethylstarch 130/0.4 = "Voluven®"
0.9 % NaCl	Active comparator	Drug: 0.9 % NaCl

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Severe sepsis
Requirement for fluid resuscitation

Key exclusion criteria (4 listed)

serum creatinine > 300µmol/L
Chronic renal failure
Anuria lasting more than 4 hours
Requirement for renal support

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
6 % Hydroxyethylstarch 130/0.4 = "Voluven®"Also: 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.	Drug	Voluven® Arm
0.9 % NaClNaCl 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.	Drug	0.9 % NaCl

Primary outcome

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.

9 secondary outcomes

Time From Start of Fluid Resuscitation With Study Drug to the Initial Hemodynamic Stabilization
Time frame: until hemodynamic stabilization (up to 48 hours)
Quantity of Study Drug in 4 Days
Time frame: 4 days
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 After Hemodynamic Stabilization
Time frame: up to 48 hours
Total Amount of Enteral Calories During the First Seven Days of Enteral Nutrition
Time frame: 7 days
Length of Stay in the Intensive Care Unit (ICU)
Time frame: Until discharge from ICU (up to day 90)
Length of Stay in the ICU
Time frame: Until discharge from ICU (up to Day 90)
Length of Stay in the Hospital
Time frame: Until discharge from hospital (up to day 90)
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

Results and safety

Results posted to the registry on 2 Aug 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Voluven® Arm	100	51
NaCl 0.9 % Arm	96	64

Primary outcome: Amount of Study Drug Required to Achieve Initial Hemodynamic Stabilization

Time frame: until hemodynamic stabilization (up to 48 hours). Mean (Standard Deviation). Unit: Milliliter

Measure	Voluven® Arm n = 88	NaCl 0.9 % Arm n = 86
Value	1379 (886)	1709 (1164)

Voluven® Arm vs NaCl 0.9 % Arm: Mean Difference (Final Values): -331 (95% CI -640 to -21), p = 0.0185, t-test, 1 sided

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

10 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Voluven® Arm	53 of 100 (53%)	99 of 100 (99%)	Not reported
NaCl 0.9 % Arm	44 of 96 (45.8%)	95 of 96 (99%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22624531Guidet 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.

Related trials for Sepsis

Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
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Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bertrand Guidet, Prof., MD study chair

Hôpital St Antoine, Réanimation Médicale

24 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 6 % Hydroxyethylstarch 130/0.4 = "Voluven®" and 0.9 % NaCl in people with Sepsis, run by Fresenius Kabi at 24 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Aug 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Amount of Study Drug Required to Achieve Initial Hemodynamic Stabilization (time frame: until hemodynamic stabilization (up to 48 hours)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00464204, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2012.