Trial Outcomes & Findings for Use of 6% Hydroxyethylstarch (130/0.4) in Cardiac Surgical Patients (NCT NCT02192502)
NCT ID: NCT02192502
Last Updated: 2023-02-14
Results Overview
To assess the safety of HES 130/0.4 (Voluven) versus albumin 5% on renal function we will measure urinary concentrations of neutrophil gelatinase-associated lipocalin (NGAL), an important marker of renal function, measured at baseline (following anesthetic induction and prior to surgical incision), at one hour of arrival to intensive care unit (ICU), at 24 hours following completion of surgery.
COMPLETED
PHASE3
149 participants
3 measurements in total from baseline to 24 hours after surgery: the first one is at baseline; the second one is at one hour of arrive to ICU and last one is at 24 hours after surgery
2023-02-14
Participant Flow
9 more patients were recruited due to withdrawal (patients did not receive any treatment).
9 more patients were recruited to ensure enough power after excluding patients who were randomized but they withdrew from the study and did not receive any treatment (see periods section for details).
Participant milestones
| Measure |
HES 130/0.4 (Voluven)
6% HES 130/0.4 during surgery
HES 130/0.4 (Voluven)
|
Human Albumin 5%
human albumin 5% during surgery
human albumin 5%
|
|---|---|---|
|
Overall Study
STARTED
|
76
|
73
|
|
Overall Study
COMPLETED
|
69
|
72
|
|
Overall Study
NOT COMPLETED
|
7
|
1
|
Reasons for withdrawal
| Measure |
HES 130/0.4 (Voluven)
6% HES 130/0.4 during surgery
HES 130/0.4 (Voluven)
|
Human Albumin 5%
human albumin 5% during surgery
human albumin 5%
|
|---|---|---|
|
Overall Study
Did not receive intervention due to euvolemia
|
4
|
1
|
|
Overall Study
did not receive intervention due to circulatory arrest
|
2
|
0
|
|
Overall Study
did not receive intervention due to logistic reasons
|
1
|
0
|
Baseline Characteristics
Use of 6% Hydroxyethylstarch (130/0.4) in Cardiac Surgical Patients
Baseline characteristics by cohort
| Measure |
HES 130/0.4 (Voluven)
n=69 Participants
6% HES 130/0.4 during surgery
HES 130/0.4 (Voluven)
|
Human Albumin 5%
n=72 Participants
human albumin 5% during surgery
human albumin 5%
|
Total
n=141 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
71 years
STANDARD_DEVIATION 10 • n=99 Participants
|
69 years
STANDARD_DEVIATION 9 • n=107 Participants
|
70 years
STANDARD_DEVIATION 9 • n=206 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=99 Participants
|
28 Participants
n=107 Participants
|
50 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=99 Participants
|
44 Participants
n=107 Participants
|
91 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
62 Participants
n=99 Participants
|
68 Participants
n=107 Participants
|
130 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Not reported
|
7 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Diabetes
Type 1
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Diabetes
Type 2
|
15 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
Hypertension
|
53 Participants
n=99 Participants
|
54 Participants
n=107 Participants
|
107 Participants
n=206 Participants
|
|
Stroke
|
6 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Myocardial infarction
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Surgery type
Aortic valve only
|
35 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
67 Participants
n=206 Participants
|
|
Surgery type
Aortic valve + CABG
|
12 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
28 Participants
n=206 Participants
|
|
Surgery type
Aortic valve + other
|
14 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
|
Surgery type
Aortic valve + CABG + other
|
8 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Duration of aortic cross-clamp
|
65 minutes
n=99 Participants
|
60 minutes
n=107 Participants
|
62 minutes
n=206 Participants
|
|
Total fluid
|
2.8 L
n=99 Participants
|
2.8 L
n=107 Participants
|
2.8 L
n=206 Participants
|
|
Transfusion
Red blood cell
|
13 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Transfusion
Platelets
|
10 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Transfusion
Fresh frozen plasma
|
8 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Transfusion
Cryoprecipitate
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Transfusion
Transfusion
|
19 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
Volume of study solution
|
500 ml
n=99 Participants
|
750 ml
n=107 Participants
|
620 ml
n=206 Participants
|
|
Previous cardiac surgery
|
13 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Use of antifibrinolytic drug
|
4 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 3 measurements in total from baseline to 24 hours after surgery: the first one is at baseline; the second one is at one hour of arrive to ICU and last one is at 24 hours after surgeryTo assess the safety of HES 130/0.4 (Voluven) versus albumin 5% on renal function we will measure urinary concentrations of neutrophil gelatinase-associated lipocalin (NGAL), an important marker of renal function, measured at baseline (following anesthetic induction and prior to surgical incision), at one hour of arrival to intensive care unit (ICU), at 24 hours following completion of surgery.
Outcome measures
| Measure |
HES 130/0.4 (Voluven)
n=69 Participants
6% HES 130/0.4 during surgery
HES 130/0.4 (Voluven)
|
Human Albumin 5%
n=72 Participants
human albumin 5% during surgery
human albumin 5%
|
|---|---|---|
|
Urine Neutrophil Gelatinase-associated Lipocalin (NGAL) [Time Frame: 24 Hours After Surgery] [Designated as Safety Issue: Yes]
at 1 hour after surgery
|
5.0 ng/ml
Interval 1.4 to 68.0
|
4.7 ng/ml
Interval 1.6 to 74.0
|
|
Urine Neutrophil Gelatinase-associated Lipocalin (NGAL) [Time Frame: 24 Hours After Surgery] [Designated as Safety Issue: Yes]
baseline
|
2.9 ng/ml
Interval 1.8 to 5.4
|
4.0 ng/ml
Interval 2.2 to 6.4
|
|
Urine Neutrophil Gelatinase-associated Lipocalin (NGAL) [Time Frame: 24 Hours After Surgery] [Designated as Safety Issue: Yes]
at 24 hours after surgery
|
12 ng/ml
Interval 6.8 to 23.0
|
15 ng/ml
Interval 7.1 to 22.0
|
SECONDARY outcome
Timeframe: within first 7 postoperative daysPostoperative kidney dysfunction using RIFLE diagnostic criteria was also assessed. Patients were assessed for risk for kidney dysfunction (RIFLE-R), injury to the kidney (RIFLE-I), failure of kidney function (RIFLE-F) using criteria based on only peak serum creatinine concentrations within the first seven postoperative days. Due to too few events, this outcome was redefined to risk (or worse) vs. no risk for this analysis. RIFLE classification criteria is listed below: Risk (RIFLE-R) Increase in serum creatinine x 1.5 from baseline Injury (RIFLE-I) Increase in serum creatinine x 2 from baseline Failure (RIFLE-F) Increase in serum creatinine x 3 from baseline Loss (RIFLE-L) Complete loss of kidney function \> 4 weeks End stage (RIFLE-E) End-stage kidney failure \> 3 months
Outcome measures
| Measure |
HES 130/0.4 (Voluven)
n=69 Participants
6% HES 130/0.4 during surgery
HES 130/0.4 (Voluven)
|
Human Albumin 5%
n=72 Participants
human albumin 5% during surgery
human albumin 5%
|
|---|---|---|
|
Kidney Function
Failure
|
1 Participants
|
0 Participants
|
|
Kidney Function
No risk
|
61 Participants
|
69 Participants
|
|
Kidney Function
Risk
|
5 Participants
|
2 Participants
|
|
Kidney Function
Injury
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: postoperative 1 hourPostop Urine IL-18 (interleukin-18) measured at 1 h of arrival to ICU
Outcome measures
| Measure |
HES 130/0.4 (Voluven)
n=69 Participants
6% HES 130/0.4 during surgery
HES 130/0.4 (Voluven)
|
Human Albumin 5%
n=72 Participants
human albumin 5% during surgery
human albumin 5%
|
|---|---|---|
|
Postop Urine IL-18
|
10 pg/ml
Interval 3.0 to 33.0
|
16 pg/ml
Interval 5.0 to 85.0
|
SECONDARY outcome
Timeframe: 24 hours after surgeryPostoperative urine IL-18 (interleukin-18) measured at 24 hours after surgery
Outcome measures
| Measure |
HES 130/0.4 (Voluven)
n=69 Participants
6% HES 130/0.4 during surgery
HES 130/0.4 (Voluven)
|
Human Albumin 5%
n=72 Participants
human albumin 5% during surgery
human albumin 5%
|
|---|---|---|
|
Postop Urine IL-18
|
60 pg/ml
Interval 37.0 to 91.0
|
53 pg/ml
Interval 29.0 to 99.0
|
POST_HOC outcome
Timeframe: within the first seven postoperative dayskidney injury using RIFLE criteria based on both peak creatinine levels and urine output, as recommended by Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group RIFLE classification criteria is listed below: Risk (RIFLE-R) Increase in serum creatinine x 1.5 from baseline urine output \< 0.5 mL/kg/hr for more than 6 hrs Injury (RIFLE-I) Increase in serum creatinine x 2 from baseline urine output \< 0.5 mL/kg/hr for more than 12 hrs Failure (RIFLE-F) Increase in serum creatinine x 3 from baseline urine output \< 0.3 mL/kg/hr for 24 hrs or anuria for 12 hrs Loss (RIFLE-L) Complete loss of kidney function \> 4 weeks End stage (RIFLE-E) End-stage kidney failure \> 3 months
Outcome measures
| Measure |
HES 130/0.4 (Voluven)
n=69 Participants
6% HES 130/0.4 during surgery
HES 130/0.4 (Voluven)
|
Human Albumin 5%
n=72 Participants
human albumin 5% during surgery
human albumin 5%
|
|---|---|---|
|
Kidney Function
Failure
|
1 Participants
|
0 Participants
|
|
Kidney Function
No risk
|
27 Participants
|
16 Participants
|
|
Kidney Function
Risk
|
18 Participants
|
24 Participants
|
|
Kidney Function
Injury
|
23 Participants
|
31 Participants
|
Adverse Events
HES 130/0.4 (Voluven)
Human Albumin 5%
Serious adverse events
| Measure |
HES 130/0.4 (Voluven)
n=69 participants at risk
6% HES 130/0.4 during surgery
HES 130/0.4 (Voluven)
|
Human Albumin 5%
n=72 participants at risk
human albumin 5% during surgery
human albumin 5%
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.9%
2/69 • Number of events 2 • 1 year
|
2.8%
2/72 • Number of events 2 • 1 year
|
|
Cardiac disorders
cardiac-related
|
18.8%
13/69 • Number of events 15 • 1 year
|
9.7%
7/72 • Number of events 7 • 1 year
|
|
Injury, poisoning and procedural complications
Injury
|
0.00%
0/69 • 1 year
|
1.4%
1/72 • Number of events 1 • 1 year
|
|
Nervous system disorders
Nervous disorder
|
2.9%
2/69 • Number of events 2 • 1 year
|
2.8%
2/72 • Number of events 2 • 1 year
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/69 • 1 year
|
1.4%
1/72 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
respiratory related event
|
7.2%
5/69 • Number of events 5 • 1 year
|
1.4%
1/72 • Number of events 1 • 1 year
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place