Cardiac Surgery, Cardiopulmonary Bypass
Conditions
Brief summary
This study will compare the clinical efficacy and safety of Voluven® and Human Albumin during elective open-heart surgery in pediatric patients.
Detailed description
In the past, human albumin has been widely accepted as the therapeutic gold standard in paediatric volume replacement therapy because of the physiological hypoproteinemia in newborns and infants. In adult patients, artificial colloids such as hydroxyethyl starch have replaced human albumin as first choice in many settings. This study will compare the clinical efficacy and safety of HES 130/0.4 (6%) in normal saline vs. HSA 50g/L in volume replacement therapy during elective open-heart surgery in paediatric patients. The hypothesis of this study is to demonstrate that HES 130/0.4 (6%) and HSA 50g/L are equivalent regarding efficacy and provide comparable safety during elective open-heart surgery in paediatric patients 2 to 12 years of age.
Interventions
DRUGHES 130/0.4 (6%) in sodium chloride (Voluven®, solution for infusion), Human serum albumin (HSA 50g/L)
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.
DRUGHuman serum albumin (HSA 50g/L)
Human serum albumin (HSA 50g/L)
Sponsors
Fresenius Kabi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Male or female paediatric patient, 2 to 12 years of age, suffering from congenital heart-disease and undergoing elective open-heart surgery requiring ECC; * Signed parental written informed consent and patient assent where achievable
Exclusion criteria
* Known contraindication against scheduled concomitant medication; * Total ECC volume \< 400 mL; * ASA \> III
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Volume of Colloid Solution Required Intraoperatively | Day 1 (intraoperatively) | Total volume of study drug plus rescue colloid, if applicable |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fluid Input | 2 days | Quantity of total fluids administered from beginning of anaesthesia until 2nd postop morning |
| Fluid Output | 2 days | Quantity of total fluids excreted or lost from beginning of anaesthesia until 2nd postop morning |
| Fluid Balance | 2 days | Balance of total fluid input and total fluid output |
| Mean Arterial Pressure (MAP) | Beginning of anaesthesia (baseline) until arrival on intensive care unit (ICU) | Mean arterial pressure (MAP) from beginning of anaesthesia (baseline) until arrival on intensive care unit (ICU) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Calculated Perioperative Red Blood Cell (RBC) Loss | 2 days | Calculated perioperative RBC loss = Predicted blood volume1 × (hematocrit \[baseline\] - hematocrit \[2nd postop morning\]) + transfused RBC volume2; 1. Predicted blood volume (mL) = 80 × body weight (kg) 2. Transfused RBC volume = 0.7 × infused packed RBC |
| Length of Stay on the Intensive Care Unit (ICU) | From admission to ICU until discharge from ICU | Length of stay (number of days) on the intensive care unit (ICU). |
| Mortality | From screening to end of follow-up | Mortality was reported for the time period from screening until the end of follow-up. |
| Acute Renal Failure (ARF) | From baseline until 2nd postop morning. | Acute renal failure was defined as a two fold increase in serum creatinine concentration over the value at baseline at any time after baseline. |
Countries
Austria, Belgium
Participant flow
Recruitment details
Participants were recruited in paediatric care units of 2 hospitals in Austria and Belgium from March 2009 (FPI) until July 2010 and were followed up until August 2010 (LPO).
Pre-assignment details
Participants were screened in paediatric care units of the participating 2 study sites in Austria and Belgium.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 31 |
| HSA 5% Arm (Comparison Group) Human Serum Albumin (HSA) 50g/L, i.v. | 30 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Main reason: Follow-up data not complete | 5 | 4 |
Baseline characteristics
| Characteristic | Voluven® Arm | HSA 5% Arm (Comparison Group) | Total |
|---|---|---|---|
| Age Continuous | 5.2 years STANDARD_DEVIATION 2.9 | 4.0 years STANDARD_DEVIATION 2 | 4.6 years STANDARD_DEVIATION 2.6 |
| Height | 106.6 cm STANDARD_DEVIATION 16.8 | 101.3 cm STANDARD_DEVIATION 12.8 | 104.0 cm STANDARD_DEVIATION 15.1 |
| Region of Enrollment Austria | 11 participants | 10 participants | 21 participants |
| Region of Enrollment Belgium | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 16 Participants | 13 Participants | 29 Participants |
| Sex: Female, Male Male | 15 Participants | 17 Participants | 32 Participants |
| Weight | 18.2 kg STANDARD_DEVIATION 8.9 | 15.4 kg STANDARD_DEVIATION 4.4 | 16.9 kg STANDARD_DEVIATION 7.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 31 | 29 / 29 |
| serious Total, serious adverse events | 11 / 31 | 7 / 29 |
Outcome results
Primary
Total Volume of Colloid Solution Required Intraoperatively
Total volume of study drug plus rescue colloid, if applicable
Time frame: Day 1 (intraoperatively)
Population: Per-protocol population (PP) = All patients in the Intention-to-treat (ITT) set without any major protocol violation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voluven® Arm | Total Volume of Colloid Solution Required Intraoperatively | 36.6 ml/kg | Standard Deviation 11.76 |
| HSA 5% Arm (Comparison Group) | Total Volume of Colloid Solution Required Intraoperatively | 36.97 ml/kg | Standard Deviation 11.86 |
Comparison: 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%.95% CI: [0.84, 1.16]ANOVA
Secondary
Fluid Balance
Balance of total fluid input and total fluid output
Time frame: 2 days
Population: Per-protocol population (PP) = All patients in the ITT set without any major protocol violation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voluven® Arm | Fluid Balance | 51.3 ml/kg | Standard Deviation 47.5 |
| HSA 5% Arm (Comparison Group) | Fluid Balance | 67.1 ml/kg | Standard Deviation 62.6 |
Secondary
Fluid Input
Quantity of total fluids administered from beginning of anaesthesia until 2nd postop morning
Time frame: 2 days
Population: Per-protocol population (PP) = All patients in the ITT set without any major protocol violation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voluven® Arm | Fluid Input | 246.8 ml/kg | Standard Deviation 119.3 |
| HSA 5% Arm (Comparison Group) | Fluid Input | 248.2 ml/kg | Standard Deviation 105.8 |
Secondary
Fluid Output
Quantity of total fluids excreted or lost from beginning of anaesthesia until 2nd postop morning
Time frame: 2 days
Population: Per-protocol population (PP) = All patients in the ITT set without any major protocol violation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voluven® Arm | Fluid Output | 195.5 ml/kg | Standard Deviation 95.7 |
| HSA 5% Arm (Comparison Group) | Fluid Output | 181.1 ml/kg | Standard Deviation 68.3 |
Secondary
Mean Arterial Pressure (MAP)
Mean arterial pressure (MAP) from beginning of anaesthesia (baseline) until arrival on intensive care unit (ICU)
Time frame: Beginning of anaesthesia (baseline) until arrival on intensive care unit (ICU)
Population: Per-protocol population (PP) = All patients in the ITT set without any major protocol violation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Voluven® Arm | Mean Arterial Pressure (MAP) | T1, before ECC (Extracorporeal circulation) | 54.0 mm Hg | Standard Deviation 7.4 |
| Voluven® Arm | Mean Arterial Pressure (MAP) | T3, after skin closure | 61.2 mm Hg | Standard Deviation 9.7 |
| Voluven® Arm | Mean Arterial Pressure (MAP) | T2, after ECC | 56.6 mm Hg | Standard Deviation 7.6 |
| Voluven® Arm | Mean Arterial Pressure (MAP) | T4, arrival on ICU | 65.3 mm Hg | Standard Deviation 14.8 |
| Voluven® Arm | Mean Arterial Pressure (MAP) | T0, Baseline | 64.1 mm Hg | Standard Deviation 11.3 |
| HSA 5% Arm (Comparison Group) | Mean Arterial Pressure (MAP) | T4, arrival on ICU | 65.2 mm Hg | Standard Deviation 8.8 |
| HSA 5% Arm (Comparison Group) | Mean Arterial Pressure (MAP) | T0, Baseline | 66.5 mm Hg | Standard Deviation 12.5 |
| HSA 5% Arm (Comparison Group) | Mean Arterial Pressure (MAP) | T1, before ECC (Extracorporeal circulation) | 51.3 mm Hg | Standard Deviation 8 |
| HSA 5% Arm (Comparison Group) | Mean Arterial Pressure (MAP) | T2, after ECC | 58.2 mm Hg | Standard Deviation 9.7 |
| HSA 5% Arm (Comparison Group) | Mean Arterial Pressure (MAP) | T3, after skin closure | 62.0 mm Hg | Standard Deviation 9.9 |
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.
Time frame: From baseline until 2nd postop morning.
Population: Safety Population (SAF) = All randomized patients treated with study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Voluven® Arm | Acute Renal Failure (ARF) | 4 Participants |
| HSA 5% Arm (Comparison Group) | Acute Renal Failure (ARF) | 4 Participants |
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; 1. Predicted blood volume (mL) = 80 × body weight (kg) 2. Transfused RBC volume = 0.7 × infused packed RBC
Time frame: 2 days
Population: Safety Population (SAF) = All randomized patients treated with study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voluven® Arm | Calculated Perioperative Red Blood Cell (RBC) Loss | 14.4 ml/kg | Standard Deviation 14.4 |
| HSA 5% Arm (Comparison Group) | Calculated Perioperative Red Blood Cell (RBC) Loss | 15.3 ml/kg | Standard Deviation 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).
Time frame: From admission to ICU until discharge from ICU
Population: Safety Population (SAF) = All randomized patients treated with study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voluven® Arm | Length of Stay on the Intensive Care Unit (ICU) | 3.1 Days |
| HSA 5% Arm (Comparison Group) | Length of Stay on the Intensive Care Unit (ICU) | 3.1 Days |
Other Pre-specified
Mortality
Mortality was reported for the time period from screening until the end of follow-up.
Time frame: From screening to end of follow-up
Population: Safety Population (SAF) = All randomized patients treated with study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Voluven® Arm | Mortality | 0 Participants |
| HSA 5% Arm (Comparison Group) | Mortality | 0 Participants |