Clinical Trial Results:
Infusion of hypertonic solutions: A risk factor for delirium after cardiac surgery? A randomised double blinded controlled trial.
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Summary
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EudraCT number |
2018-002385-39 |
Trial protocol |
SE |
Global end of trial date |
26 Jun 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Jun 2021
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First version publication date |
03 Jun 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
HSPOD
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
County Council of Västerbotten
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Sponsor organisation address |
Heart Center, University Hospital of Umeå, Umeå, Sweden,
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Public contact |
Fredrik Holmner, County Council of Västerbotten, 046 0907853650, fredrik.holmner@vll.se
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Scientific contact |
Fredrik Holmner, County Council of Västerbotten, 046 0907853650, fredrik.holmner@vll.se
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Jun 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Jun 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Jun 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Are hypertonic solutions a risk factor for delirium after cardiac surgery?
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Protection of trial subjects |
All patients was informed about the strict confidentiality of their patient data, but that their medical records may be reviewed for trial purposes by authorized individuals other than their treating physician
Personal data was processed in a legal, correct and open manner, collected for specific, explicit and legitimate purposes, adequate and relevant, correct and updated. Personal data are stored in a form that allows identification of the data patient for a longer time than is necessary and was treated in a manner that ensures appropriate security.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Apr 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Sweden: 205
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Worldwide total number of subjects |
205
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EEA total number of subjects |
205
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1
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From 65 to 84 years |
204
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were enrolled consecutively and upon availability at Umeå Heart Centre, Umeå University Hospital, Sweden, between April 2019 and June 2020 | |||||||||||||||||||||
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Pre-assignment
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Screening details |
205 patients were included, 200 were randomised | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Data analyst | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Test group | |||||||||||||||||||||
Arm description |
Cardiac surgical patients requiring cardiopulmonary bypass randomised to: Priming of the heart-lung machine: Ringer-Acetate 1000 ml + Mannitol 60 g + Sodium Chloride 160 mmol + Heparin 10 000 IU | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Ringer-Acetate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intraarterial use
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Dosage and administration details |
1000 ml administered at commence of cardiopulmonary bypass as a single dose. Included in
the prime composition used to fill the components of the heart-lung machine.
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Investigational medicinal product name |
Mannitol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intraarterial use
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Dosage and administration details |
60 g administered at commence of cardiopulmonary bypass as a single dose. Included in
the prime composition used to fill the components of the heart-lung machine.
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Investigational medicinal product name |
Sodium chloride
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for concentrate for solution for infusion
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Routes of administration |
Intraarterial use
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Dosage and administration details |
160 mmol administered at commence of cardiopulmonary bypass as a single dose. Included in the prime composition used to fill the components of the heart-lung machine.
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Investigational medicinal product name |
Heparin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection/infusion
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Routes of administration |
Intraarterial use
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Dosage and administration details |
10 000 IU administered at commence of cardiopulmonary bypass as a single dose. Included in
the prime composition used to fill the components of the heart-lung machine.
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Arm title
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Comparison group | |||||||||||||||||||||
Arm description |
Cardiac surgical patients requiring cardiopulmonary bypass randomised to: Priming of the heart-lung machine: Ringer-Acetate 1400 ml + Heparin 10 000 IU | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Ringer-Acetate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intraarterial use
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Dosage and administration details |
1400 ml administered at commence of cardiopulmonary bypass as a single dose. Included in
the prime composition used to fill the components of the heart-lung machine.
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Investigational medicinal product name |
Heparin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection/infusion
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Routes of administration |
Intraarterial use
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Dosage and administration details |
10 000 IU administered at commence of cardiopulmonary bypass as a single dose. Included in
the prime composition used to fill the components of the heart-lung machine.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 205 patients were included, only 200 were randomised due to change of ECC method after inclusion (heparin coated CPB system) |
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Baseline characteristics reporting groups
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Reporting group title |
Test group
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Reporting group description |
Cardiac surgical patients requiring cardiopulmonary bypass randomised to: Priming of the heart-lung machine: Ringer-Acetate 1000 ml + Mannitol 60 g + Sodium Chloride 160 mmol + Heparin 10 000 IU | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Comparison group
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Reporting group description |
Cardiac surgical patients requiring cardiopulmonary bypass randomised to: Priming of the heart-lung machine: Ringer-Acetate 1400 ml + Heparin 10 000 IU | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Test group
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Reporting group description |
Cardiac surgical patients requiring cardiopulmonary bypass randomised to: Priming of the heart-lung machine: Ringer-Acetate 1000 ml + Mannitol 60 g + Sodium Chloride 160 mmol + Heparin 10 000 IU | ||
Reporting group title |
Comparison group
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Reporting group description |
Cardiac surgical patients requiring cardiopulmonary bypass randomised to: Priming of the heart-lung machine: Ringer-Acetate 1400 ml + Heparin 10 000 IU | ||
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End point title |
Delirium | |||||||||
End point description |
Assessment delirium is performed by executing the following test battery:
1. Mini Mental State Examination (MMSE)
2. Geriatric Depression Scale-15 (GDS-15)
3. Katz ADL-stair case test
4. Barthel index
5. NRS Pain
6. Organic Brain Syndrome Scale (OBS)
7. The Nursing Delirium Screening Scale (Nu-DESC)
8. Richmond agitation sedation scale (RASS)
9. Glasgow coma scale (GCS)
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End point type |
Primary
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End point timeframe |
Assessed before and 1 day and 3 days after surgery
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Statistical analysis title |
Difference postoperative delirium | |||||||||
Comparison groups |
Test group v Comparison group
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Number of subjects included in analysis |
195
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||
Confidence interval |
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| Notes [1] - The standard test for categorical variables with a large sample size will be analysed by the Chi-square test. Fisher’s test will be executed in test situations, when the cell frequence in a contingency table is small, typically less than 5. In addition, differences of test scores between test and comparison group for the employed tests will be reported and analysed statistically using the Mann-Withney u-test. Test scores represent data on the ordinal scale. |
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End point title |
Plasma osmolality | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Plasma osmolality is measured intraoperatively and twice postoperatively (day 1 and day 3).
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the time a patient receives the first dose of study treatment until 24 hours thereafter.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5
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Reporting groups
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Reporting group title |
Test group
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Reporting group description |
Cardiac surgical patients requiring cardiopulmonary bypass randomised to: Priming of the heart-lung machine: Ringer-Acetate 1000 ml + Mannitol 60 g + Sodium Chloride 160 mmol + Heparin 10 000 IU | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Comparison group
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Reporting group description |
Cardiac surgical patients requiring cardiopulmonary bypass randomised to: Priming of the heart-lung machine: Ringer-Acetate 1400 ml + Heparin 10 000 IU | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
