Voluven® in Paediatric Patients | NCT00860405

Voluven® in Paediatric Patients | NCT00860405 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1	Experimental	Investigational drug: HES 130/0.4 (6%) in sodium chloride (Voluven®, solution for infusion)	Drug: HES 130/0.4 (6%) in sodium chloride (Voluven®, solution for infusion), Human serum albumin (HSA 50g/L)
2	Active Comparator	Control drug: Human serum albumin (HSA 50g/L)	Drug: Human serum albumin (HSA 50g/L)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
HES 130/0.4 (6%) in sodium chloride (Voluven®, solution for infusion), Human serum albumin (HSA 50g/L)	Drug	Study medication will be given as part of the priming of the ECC and for plasma volume replacement after start of ECC up to the maximum dosage of 50 mL/kg body weight/day.

Outcomes Module

Measure	Description	Time Frame
Total Volume of Colloid Solution Required Intraoperatively	Total volume of study drug plus rescue colloid, if applicable	Day 1 (intraoperatively)

Secondary Outcomes

Measure	Description	Time Frame
Mean Arterial Pressure (MAP)	Mean arterial pressure (MAP) from beginning of anaesthesia (baseline) until arrival on intensive care unit (ICU)	Beginning of anaesthesia (baseline) until arrival on intensive care unit (ICU)
Fluid Input

Other Outcomes

Measure	Description	Time Frame
Calculated Perioperative Red Blood Cell (RBC) Loss	Calculated perioperative RBC loss = Predicted blood volume1 × (hematocrit [baseline] - hematocrit [2nd postop morning]) + transfused RBC volume2; Predicted blood volume (mL) = 80 × body weight (kg) Transfused RBC volume = 0.7 × infused packed RBC	2 days

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Philippe Van der Linden, Professor	HUDERF - Hôpital Universitaire des Enfants Reine Fabiola	Principal Investigator
Hans Gombotz, Professor	AKh Allgemeines Krankenhaus der Stadt Linz GmbH	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
AKh Allgemeines Krankenhaus der Stadt Linz GmbH		Linz		4021	Austria
HUDERF - Hôpital Universitaire des Enfants Reine Fabiola

Arm/Group Information

ID	Title	Description
FG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
FG001	HSA 5% Arm (Comparison Group)	Human Serum Albumin (HSA) 50g/L, i.v.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00031 subjects FG00130 subjects
Completed Treatment		FG00031 subjects FG00129 subjects
Day 28 Follow-up Performed		FG00031 subjects FG00129 subjects
COMPLETED		FG00026 subjectscompleted overall study FG00126 subjects
NOT COMPLETED		FG0005 subjects FG0014 subjects

Type	Comment	Reasons
Main reason: Follow-up data not complete		FG0005 subjects FG0014 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
BG001	HSA 5% Arm (Comparison Group)

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Total Volume of Colloid Solution Required Intraoperatively

Total volume of study drug plus rescue colloid, if applicable

Per-protocol population (PP) = All patients in the Intention-to-treat (ITT) set without any major protocol violation.

Posted

Mean

Standard Deviation

ml/kg

Day 1 (intraoperatively)

ID	Title	Description
OG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
OG001	HSA 5% Arm (Comparison Group)	Human Serum Albumin (HSA) 50g/L, i.v.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Coagulopathy	Blood and lymphatic system disorders	MedDRA Version 13.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 13.0	Systematic Assessment

More Info Module

Certain Agreements

Point of Contact

Title	Organization	Phone	Extension	Email
Professor Dr. Martin Westphal, Chief Medical Officer	Fresenius Kabi Aktiengesellschaft, Else-Kröner-Str. 1, 61352 Bad Homburg, Germany	+49 6172 686 7280		martin.westphal@fresenius-kabi.com

Intervention Browse Module

ID	Term
D006895	Hydroxyethyl Starch Derivatives
D012965	Sodium Chloride
C485123	HES 130-0.4
D012996	Solutions
D000075462	Serum Albumin, Human

ID	Term
D013213	Starch
D004040	Dietary Carbohydrates
D002241	Carbohydrates
D005936	Glucans

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The aim of the study was to prove equivalence, i.e. H0: μVoluven/μHSA ≤ 0.55 or μVoluven/μHSA ≥ 1.82 H1: 0.55 < μVoluven/μHSA < 1.82 where μVoluven was the mean infused volume of Voluven® and μHSA was the mean infused volume of HSA 5%.	ANOVA	Primary endpoint specified + analysed for PP and ITT population. Confirmatory analysis based on PP population only, no adjustment for multiplicity.		Null hypothesis tested by calculating a 2-sided 95% CI for ratio of LS-means μVoluven/μHSA based on ANOVA incl.treatment+centre as effects. If 95% CI was within equivalence range(0.55, 1.82), significant equivalence was concluded (Type I error: 2.5%)	Ratio of LS-means	0.98			2-Sided	95	0.84	1.16			Considered ratio: μVoluven/μHSA = LS-mean of Voluven®/LS-mean of HSA 5%	Yes	Non-Inferiority or Equivalence	Assuming a coefficient of variation of 0.363 and a desired power of 90 % with a type I level of 2.5 %, N=11 patients per treatment group were needed. The power was calculated by means of the software SAS, version 9.1.3, PROC POWER. Nevertheless, more patients were required for the assessment of safety, therefore 2 × 30 patients were planned to be included in this study.

Secondary

Mean Arterial Pressure (MAP)

Mean arterial pressure (MAP) from beginning of anaesthesia (baseline) until arrival on intensive care unit (ICU)

Per-protocol population (PP) = All patients in the ITT set without any major protocol violation

Posted

Mean

Standard Deviation

mm Hg

Beginning of anaesthesia (baseline) until arrival on intensive care unit (ICU)

ID	Title	Description
OG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
OG001	HSA 5% Arm (Comparison Group)	Human Serum Albumin (HSA) 50g/L, i.v.

Units	Counts
Participants	OG00029 OG00126

Title

Denominators

Categories

T0, Baseline

Title	Measurements
	OG00064.1± 11.3 OG00166.5± 12.5

T1, before ECC (Extracorporeal circulation)

Title	Measurements
	OG000

Secondary

Fluid Input

Quantity of total fluids administered from beginning of anaesthesia until 2nd postop morning

Per-protocol population (PP) = All patients in the ITT set without any major protocol violation

Posted

Mean

Standard Deviation

ml/kg

2 days

ID	Title	Description
OG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
OG001	HSA 5% Arm (Comparison Group)	Human Serum Albumin (HSA) 50g/L, i.v.

Units	Counts
Participants	OG00029 OG00126

Title

Denominators

Categories

Title	Measurements
	OG000246.8± 119.3 OG001248.2± 105.8

Secondary

Fluid Output

Quantity of total fluids excreted or lost from beginning of anaesthesia until 2nd postop morning

Per-protocol population (PP) = All patients in the ITT set without any major protocol violation.

Posted

Mean

Standard Deviation

ml/kg

2 days

ID	Title	Description
OG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
OG001	HSA 5% Arm (Comparison Group)	Human Serum Albumin (HSA) 50g/L, i.v.

Units	Counts
Participants	OG00029 OG00126

Title

Denominators

Categories

Title	Measurements
	OG000195.5± 95.7 OG001181.1± 68.3

Secondary

Fluid Balance

Balance of total fluid input and total fluid output

Per-protocol population (PP) = All patients in the ITT set without any major protocol violation.

Posted

Mean

Standard Deviation

ml/kg

2 days

ID	Title	Description
OG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
OG001	HSA 5% Arm (Comparison Group)	Human Serum Albumin (HSA) 50g/L, i.v.

Units	Counts
Participants	OG00029 OG00126

Title

Denominators

Categories

Title	Measurements
	OG00051.3± 47.5 OG00167.1± 62.6

Other Pre-specified

Calculated Perioperative Red Blood Cell (RBC) Loss

Calculated perioperative RBC loss = Predicted blood volume1 × (hematocrit [baseline] - hematocrit [2nd postop morning]) + transfused RBC volume2;

Predicted blood volume (mL) = 80 × body weight (kg)
Transfused RBC volume = 0.7 × infused packed RBC

Safety Population (SAF) = All randomized patients treated with study drug.

Posted

Mean

Standard Deviation

ml/kg

2 days

ID	Title	Description
OG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
OG001	HSA 5% Arm (Comparison Group)	Human Serum Albumin (HSA) 50g/L, i.v.

Units	Counts
Participants	OG00031 OG00129

Title

Denominators

Categories

Title	Measurements
	OG00014.4± 14.4 OG00115.3± 15.5

Other Pre-specified

Length of Stay on the Intensive Care Unit (ICU)

Length of stay (number of days) on the intensive care unit (ICU).

Safety Population (SAF) = All randomized patients treated with study drug.

Posted

Median

Inter-Quartile Range

Days

From admission to ICU until discharge from ICU

ID	Title	Description
OG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
OG001	HSA 5% Arm (Comparison Group)	Human Serum Albumin (HSA) 50g/L, i.v.

Units	Counts
Participants	OG00031 OG00129

Title

Denominators

Categories

Title	Measurements
	OG0003.1(2.0 to 5.8) OG0013.1(2.3 to 6.9)

Other Pre-specified

Mortality

Mortality was reported for the time period from screening until the end of follow-up.

Safety Population (SAF) = All randomized patients treated with study drug

Posted

Number

Participants

From screening to end of follow-up

ID	Title	Description
OG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
OG001	HSA 5% Arm (Comparison Group)	Human Serum Albumin (HSA) 50g/L, i.v.

Units	Counts
Participants	OG00031 OG00129

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

Other Pre-specified

Acute Renal Failure (ARF)

Acute renal failure was defined as a two fold increase in serum creatinine concentration over the value at baseline at any time after baseline.

Safety Population (SAF) = All randomized patients treated with study drug.

Posted

Number

Participants

From baseline until 2nd postop morning.

ID	Title	Description
OG000	Voluven® Arm	6% Hydroxyethylstarch 130/0.4, i.v. Voluven® rates were not to exceed 50 mL/kg/day; if additional study drug was required, 5% HSA was provided as rescue colloid.
OG001	HSA 5% Arm (Comparison Group)	Human Serum Albumin (HSA) 50g/L, i.v.

Units	Counts
Participants	OG00031 OG00129

Title

Denominators

Categories

Title	Measurements
	OG0004 OG0014