Clinical Trial Results:
Highdose steroid for total knee arthroplasty - A randomized doubleblindet controlled trial.
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Summary
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EudraCT number |
2018-002634-20 |
Trial protocol |
DK |
Global end of trial date |
01 Feb 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Sep 2022
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First version publication date |
26 Sep 2022
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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 |
NBF_HK_01_2018
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03758170 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Hvidovre Hospital
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Sponsor organisation address |
Kettegaards alle 30, Hvidovre, Denmark, 2650
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Public contact |
Research group, anaesthesia Dept., Anaesthesia Department, Hvidovre Hospital, Capital Region of Denmark, +45 38623862, Nicolai.Bang.Foss@regionH.dk
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Scientific contact |
Research group, anaesthesia Dept., Anaesthesia Department, Hvidovre Hospital, Capital Region of Denmark, +45 38623862, Nicolai.Bang.Foss@regionH.dk
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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 |
01 Mar 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jan 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Feb 2022
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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 |
To investigate the amount of patients with VAS >30 in a 5-meter walk test, 24 hours postoperatively efter total kneearthroplasty.
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Protection of trial subjects |
All patients had standardized care, surgery, and treatments as part of a Fast-track surgery regimen in
Total Knee Arthroplasty surgery, and both study-treatment-groups had active treatment (standard-dose
vs. higher dose).
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Background therapy |
Multimodal opioid-sparring analgesia including Cox-2 inhibitors, acetaminophen(paracetamol) and rescue opioids (morphine or oxycodone). All patients had pre- and postoperative tranexamic acid. Thromboprophylaxis was used in-hospital only (xarelto or eliquis). All patients had neuraxial anesthesia with bupivacaine. | ||
Evidence for comparator |
The use of steroids as a perioperative mean of reducing postoperative stress and hence reducing postoperative pain is well-known, and several articles exist on the topic. Lunn TH, Andersen LO, Kristensen BB, Husted H, Gaarn-Larsen L, Bandholm T, Ladelund S, Kehlet H: Effect of high-dose preoperative methylprednisolone on recovery after total hip arthroplasty: A randomized, double-blind, placebo-controlled trial. Br J Anaesth 2013; 110:66–73 De Oliveira GS, Almeida MD, Benzon HT, McCarthy RJ. Perioperative single dose systemic dexamethasone for postoperative pain: A meta-analysis of randomized controlled trials. Anesthesiology 2011; 115: 575–88 C.C. Jørgensen, F.T. Pitter, H. Kehlet Safety aspects of preoperative high-dose glucocorticoid in primary total knee replacement Br J Anaesth, 119 (2017), pp. 267-275 A. Toner, V. Ganeshanathan, M. Chan, K. Ho, T. Corcoran Safety of perioperative glucocorticoids in elective noncardiac surgery, a systematic review and metaanalysis Anesthesiology, 126 (2017), pp. 234-248 | ||
Actual start date of recruitment |
03 Dec 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Denmark: 157
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Worldwide total number of subjects |
157
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EEA total number of subjects |
157
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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) |
40
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From 65 to 84 years |
113
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85 years and over |
4
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Recruitment
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Recruitment details |
Patients were recruited before surgery at their information meeting. All participants had had oral and written project information in accordance with guidelines and had at least 24 hours of consideration. All participants gave informed consent. Patients were screened at Hvidovre Hospital and Vejle sygehus from January 2019 to September 2021 | |||||||||
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Pre-assignment
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Screening details |
From January 29, 2019, to september 31, 2021, a total of 1277 patients planned for hip arthroplasty were assessed for inclusion in accordance with inclusion and exclusion criteria. 75% of screened patients were eligible and 160 patients were included and 157 randomized. | |||||||||
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Period 1
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Period 1 title |
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, Monitor, Data analyst, Carer, Assessor | |||||||||
Blinding implementation details |
Randomization sequence were made by unblinded physicians not otherwise connected to the study or
the participants with double-control.
Study-specific trained unblinded nurses at each site, not having any contact with the participants were
responsible for preparing the study drug and blinding this for all other personnel.
Study-drug was mixed into a blinded 100 ml. container, and intervention and control were alike in both
volume and appearance.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intervention | |||||||||
Arm description |
Intervention arm, High dose Dexamethasone 1mg/kg of patient's actual bodyweight. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Dexamethasone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Dexamethasone 10mg/ml, added to a 100 ml. NaCl container in accordance with the patient's actual
weight, thus the intervention dose was 1mg/kg.
Infusion initiated after application of neuraxial anesthesia and administered within 10-15 minutes.
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Arm title
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Intermediate comparator | |||||||||
Arm description |
Intermediate dose dexamethasone 0.3mg/kg of actual bodyweight | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Dexamethasone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Concentrate for solution for infusion
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Dosage and administration details |
Dexamethasone 10mg/ml, added to a 100 ml. NaCl container in accordance to the patient's actual
weight, thus the intervention dose was 0.3mg/kg.
Infusion initiated after application of neuraxial anesthesia and administered within 10-15 minutes.
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Baseline characteristics reporting groups
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Reporting group title |
Intervention
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Reporting group description |
Intervention arm, High dose Dexamethasone 1mg/kg of patient's actual bodyweight. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Intermediate comparator
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Reporting group description |
Intermediate dose dexamethasone 0.3mg/kg of actual bodyweight | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Intervention
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Reporting group description |
Intervention arm, High dose Dexamethasone 1mg/kg of patient's actual bodyweight. | ||
Reporting group title |
Intermediate comparator
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Reporting group description |
Intermediate dose dexamethasone 0.3mg/kg of actual bodyweight | ||
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End point title |
Primary Outcome: Percentage of patients experiencing VAS>30mm on a 0-100 mm. VAS scale 24 hours after surgery upon ambulation | |||||||||||||||
End point description |
Percentage of patients experiencing VAS>30mm on a 0-100 mm VAS scale 24 hours after surgery upon
ambulation in a 5 meter walk test.
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End point type |
Primary
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End point timeframe |
24 hours after knee replacement surgery (a timeframe of 1 hour before and after precise timepoint of
end of surgery).
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Statistical analysis title |
Chi squared primary outcome | |||||||||||||||
Comparison groups |
Intervention v Intermediate comparator
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Number of subjects included in analysis |
157
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
= 0.65 | |||||||||||||||
Method |
Chi-squared | |||||||||||||||
Parameter type |
Risk ratio (RR) | |||||||||||||||
Point estimate |
1.07
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
0.8 | |||||||||||||||
upper limit |
1.4 | |||||||||||||||
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End point title |
PAIN (VAS-score) 24hours after surgery upon ambulation | ||||||||||||
End point description |
VAS-score upon ambulation in a 0-100mm. VAS scale upon a 5 meter walk test 24 hours after surgery.
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End point type |
Secondary
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End point timeframe |
24 hours after surgery (prespecified timeframe of 1 hour before and after actual end of surgery
timepoint).
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Statistical analysis title |
Mann whitney | ||||||||||||
Comparison groups |
Intervention v Intermediate comparator
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Number of subjects included in analysis |
157
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.88 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
VAS>30mm 24hours after surgery upon rest | |||||||||||||||
End point description |
Percentage of patients experiencing VAS>30mm upon rest in a 0-100mm. VAS scale 24 hours after
surgery.
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End point type |
Secondary
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End point timeframe |
24 hours after surgery (prespecified timeframe of 1 hour before and after actual end of surgery
timepoint).
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
CRP after surgery | ||||||||||||
End point description |
C-reactive protein (CRP) as a measure of inflammatory response (mg/L)
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End point type |
Secondary
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End point timeframe |
24 and 48 hour after surgery
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
Serious adverse events were reported on day 0, 1, 2, 7, 30 or 90, or when alerted via our electronic
patient record-system, and all SAE were reported within 24h of alert to the Sponsor.
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Adverse event reporting additional description |
Only Serious adverse events were recorded and reported in accordance with the approval of the Danish
medicines agency and local ethics committee, as Dexamethasone is a broadly used and well-approved
drug.
If adverse events (not serious adverse events) were reported or suspected of occurring in more than 5%
of patients, the sponsor was informed.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.0
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Reporting groups
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Reporting group title |
Intervention 1mg/kg
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Reporting group description |
Intervention arm, High dose Dexamethasone 1mg/kg of patient's actual bodyweight. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Intermediate 0.3 mg/kg
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Reporting group description |
Intermediate dose dexamethasone 0.3mg/kg of actual bodyweight | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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: No non-serious adverse events were recorded, as accepted in the protocol by the local ethics committee and DKMA |
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||||||
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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 | |||||||
