Clinical Trial Results:
A comparison of crystalloids vs. colloids for intraoperative goal-directed fluid management
|
Summary
|
|
EudraCT number |
2005-004602-86 |
Trial protocol |
AT |
Global end of trial date |
31 Dec 2016
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
26 Mar 2021
|
First version publication date |
26 Mar 2021
|
Other versions |
|
Summary report(s) |
Effect of Intraoperative Goal-directed Balanced Crystalloid versus Colloid Administration on Major Postoperative Morbidity |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
EK431/2005
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT00517127 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Medical University of Vienna
|
||
Sponsor organisation address |
Spitalgasse 23, Vienna, Austria, 1090
|
||
Public contact |
Barbara Kabon MD, Medical University of Vienna, 0043 1404004102, barbara.kabon@hotmail.com
|
||
Scientific contact |
Barbara Kabon MD, Medical University of Vienna, 0043 1404004102, barbara.kabon@hotmail.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
24 Oct 2016
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
15 Jul 2016
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
31 Dec 2016
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
1. To test whether colloid-based goal-directed intraoperative fluid management leads to less perioperative morbidity compared to crystalloid-based goal-directed intraoperative fluid management.
|
||
Protection of trial subjects |
Daily blinded follow-up till discharge
30 day follow up
4 interim analysis
Recording of maximal in-hospital Serum Creatinine concentrations and as available within 6 postoperative months
|
||
Background therapy |
NA | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
03 May 2006
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Austria: 548
|
||
Country: Number of subjects enrolled |
United States: 554
|
||
Worldwide total number of subjects |
1102
|
||
EEA total number of subjects |
548
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
752
|
||
From 65 to 84 years |
350
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||||||||||
Recruitment details |
Recruitment Period: September 2006 bis December 2016, Recruitment territories: Austria, USA | ||||||||||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||||||||||
Screening details |
Open or laparoscopic-assisted abdominal surgery expected to last at least 2 h who were age 18 to 80 yr, were American Society of Anesthesiologists (ASA) physical status I–III, body mass index of less than 35 kg/m2. Exclusion:compromised kidney function or cardiac insufficiency, severe COPD, coagulopathies, oesophageal or aortic abnormalities. | ||||||||||||||||||||||||||||||
|
Pre-assignment period milestones
|
|||||||||||||||||||||||||||||||
Number of subjects started |
1102 | ||||||||||||||||||||||||||||||
Number of subjects completed |
1102 | ||||||||||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||||||||||
Period 1 title |
Overall Trial (overall period)
|
||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||||||||||||||||||||
Blinding implementation details |
Postoperative Follow-up day by day and 30 d postoperative by a blinded Investigator
|
||||||||||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||||||||
|
Arm title
|
Crystalloid | ||||||||||||||||||||||||||||||
Arm description |
goal-directed crystalloid administration | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lactated Ringer' Solution
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||
Routes of administration |
Intravenous bolus use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
250 mL lactated Ringersolution repeatedly according to Esophageal Doppler readings
|
||||||||||||||||||||||||||||||
|
Arm title
|
Colloid | ||||||||||||||||||||||||||||||
Arm description |
goal-directed colloid administration | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Voluven
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
B05AA07
|
||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||||||||
Routes of administration |
Intravenous bolus use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
250 mL Bolus administration according to Esophageal Doppler readings, up to a maximum of 30 mL/kg /d
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Crystalloid
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
goal-directed crystalloid administration | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Colloid
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
goal-directed colloid administration | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Crystalloid
|
||
Reporting group description |
goal-directed crystalloid administration | ||
Reporting group title |
Colloid
|
||
Reporting group description |
goal-directed colloid administration | ||
|
||||||||||
End point title |
Primary Endpoint | |||||||||
End point description |
The primary outcome was postoperative morbidity,defined by a composite of major complications.
It included cardiac, pulmonary, infectious, gastrointestinal,renal, and coagulation complication.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
30 postoperative days
|
|||||||||
|
||||||||||
Statistical analysis title |
Estimated relative risk | |||||||||
Statistical analysis description |
We assessed the treatment effect on the major complications via a common effect “global” relative risk estimated
across six outcomes of interest. In this multivariate analysis,each patient was represented once for each outcome
event.
The within-subject correlation among the outcomes was accounted for using a generalized estimating equation model with an unstructured working correlation matrix.
|
|||||||||
Comparison groups |
Crystalloid v Colloid
|
|||||||||
Number of subjects included in analysis |
1057
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority [1] | |||||||||
P-value |
< 0.05 | |||||||||
Method |
multivariate analysis | |||||||||
Parameter type |
Risk ratio (RR) | |||||||||
Point estimate |
0.9
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.65 | |||||||||
upper limit |
1.23 | |||||||||
| Notes [1] - As a sensitivity analysis we assessed the treatment effect n the collapsed composite of the six major complications, i.e., any vs. none using a chi-square test. |
||||||||||
|
||||||||||
End point title |
Secondary and Tertiary Outcomes | |||||||||
End point description |
We assessed the treatment effect on the collapsed composite
of any minor complication and on a collapsed composite of
any major complications plus 30-day mortality and 30-day
readmission
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
30 postoperative days
|
|||||||||
|
||||||||||
Statistical analysis title |
Secondary and Tertiary Outcomes | |||||||||
Statistical analysis description |
The minor complication analysis was a per-protocol analysis because more than 10% of patients (n = 145) had at least one minor component missing,making an intention-to-treat analysis with conservative assignment unrealistic.
Duration of hospitalization and readmission were analyzed as time to discharge alive and time to readmission, and the treatment effects were assessed using Cox proportional hazard models.
|
|||||||||
Comparison groups |
Colloid v Crystalloid
|
|||||||||
Number of subjects included in analysis |
1057
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority [2] | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Risk ratio (RR) | |||||||||
Point estimate |
0.89
|
|||||||||
Confidence interval |
||||||||||
level |
98.3% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.69 | |||||||||
upper limit |
1.14 | |||||||||
| Notes [2] - To avoid bias from considering early deaths as short hospitalizations and thus favorable lengths of stay, patients who died in the hospital were assigned the ongest observed hospital stay of any patient and censored at that time (i.e., not discharged alive). Patients who died within 30 days after surgery were censored at the date of death for the time to readmission analysis. Because only 1% of patients died within 30 days, a competing risks analysis was unnecessary. l |
||||||||||
|
|||||||||||||
End point title |
Safety Outcome | ||||||||||||
End point description |
We compared colloids and crystalloids groups on the maximum postoperative serum creatinine concentration during hospitalization and within 6 months thereafter with analysis of covariance adjusted for the preoperative
serum creatinine
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
up to 6 month
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Safety Analysis | ||||||||||||
Statistical analysis description |
Maximum postoperative serum creatinine concentration during hospitalization and within 6 months thereafter with analysis of covariance adjusted for the preoperative serum creatinine
Because serum creatinine concentrations were not normally distributed, we analyzed them on
a log scale, with treatment effect reported as the ratio of geometric means.
We also assessed between-group differences in creatinine changes over time using linear mixed model
|
||||||||||||
Comparison groups |
Crystalloid v Colloid
|
||||||||||||
Number of subjects included in analysis |
1057
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Ratio geometric means | ||||||||||||
Parameter type |
Ratio geometric means | ||||||||||||
Point estimate |
0.97
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.93 | ||||||||||||
upper limit |
1.02 | ||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information [1]
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
30 postoperative days
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Daily follow-up during till discharge and 30 days follow-up call
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm 1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Goal-directed crystalloid administration | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm 2
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Goal-directed colloid administration | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: In this study, these were not defined |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
24 Oct 2011 |
Amendment to the protocol:
Changes in conduct of the trial- primary outcome, inclusion criteria
Change of the Principal Investigator,
Addition of sites
|
||
22 Dec 2014 |
Amendment to the protocol
Changes in conduct of the Trial: IMP maximum dosage reduced
Primary outcome extended
|
||
16 Dec 2015 |
Amendment to the protocol
Changes in interpretation of scientific document.... changes of primary outcome parameter
Addition of sites
|
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/30882476 |
|||
