Clinical Trial Results:
Effect of high versus low dose intravenous dexamethason on complications in the immediate postoperative setting after mastectomy - a randomized, double-blind, controlled trial
Summary
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EudraCT number |
2017-000227-27 |
Trial protocol |
DK |
Global end of trial date |
29 Apr 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Nov 2019
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First version publication date |
06 Nov 2019
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Other versions |
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 |
DEXMAS01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03125941 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Rigshospitalet
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Sponsor organisation address |
Blegdamsvej 9, Copenhagen, Denmark, 2100
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Public contact |
Kristin Julia Steinthorsdottir, Rigshospitalet, 0045 31666112, kste0050@regionh.dk
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Scientific contact |
Kristin Julia Steinthorsdottir, Rigshospitalet, 0045 +4531666112, kste0050@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 |
21 Oct 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Apr 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Apr 2018
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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 effect of high versus low dose intravenous dexamethasone on complications in the immediate postoperative setting after mastectomy. Main objective is proportion of patientes needing admission to postanaesthesia care unit after operation.
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Protection of trial subjects |
Study medication was medication already being used, just in two different doses
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Background therapy |
All other therapy followed local standard protocol | ||
Evidence for comparator |
4-8 mg of dexamethasone is a standard prohylactic treatment for post-operative nausea and vomiting. 125 mg methylprednisolone (equivalent to 24 mg of dexamethasone) has been shown to reduce pain in the first days after hip and knee replacements (Lunn TH, 2011, 2013). | ||
Actual start date of recruitment |
03 Apr 2017
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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: 130
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Worldwide total number of subjects |
130
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EEA total number of subjects |
130
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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) |
51
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From 65 to 84 years |
74
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85 years and over |
5
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Recruitment
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Recruitment details |
recruitment by investigator or study personell at the pre-operative consultation, at the department of breast surgery | |||||||||||||||
Pre-assignment
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Screening details |
Screening by doctors from the department of breast surgery and investigator: all adult patients undergoing mastectomy were screened for inclusion | |||||||||||||||
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, Monitor, Data analyst, Carer, Assessor | |||||||||||||||
Blinding implementation details |
Personnel not otherwise involved in trial prepared study drug: either 6 ml dexamethasone (24 mg) or 2 ml dexamethasone (8 mg) and 4 ml nacl. Syringes containing both solutions were clear and identical in appearence.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Dexamethasone 8 mg | |||||||||||||||
Arm description |
Single-shot preoperative injection | |||||||||||||||
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 |
Concentrate and solvent for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
8 mg (2 ml) with 4 ml nacl, injected single-shot
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Arm title
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Dexamethasone 24 mg | |||||||||||||||
Arm description |
Single shot pre-operative injection, 24 mg | |||||||||||||||
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 |
Concentrate and solvent for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
24 mg (6 ml) injected as a pre-operative single-shot
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
130 patients were randomized, 3 pre-intervention exclusions, so 127 received the intervention. Baseline characteristics reported for all patients, endpoints only for patients receiving intervention | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Dexamethasone 8 mg
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Reporting group description |
Single-shot preoperative injection | ||
Reporting group title |
Dexamethasone 24 mg
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Reporting group description |
Single shot pre-operative injection, 24 mg |
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End point title |
proportion of patients transferred to PACU | |||||||||
End point description |
Proportion of patients transferred to the post-anesthesia care unit after operation (vs. patients transferred directly to the ward)
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End point type |
Primary
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End point timeframe |
1 hour
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Notes [1] - 1 pre-intervention exclusion [2] - 2 pre-intervention exclusion |
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Statistical analysis title |
Primary endpoint | |||||||||
Statistical analysis description |
patients meeting criteria for transfer to PACU according to standardized discharge score
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Comparison groups |
Dexamethasone 8 mg v Dexamethasone 24 mg
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Number of subjects included in analysis |
127
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
> 0.999 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.49 | |||||||||
upper limit |
2.05 |
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End point title |
Discharge scores | |||||||||||||||||||||
End point description |
Standardized discharge score (modified Aldrete criteria), at extubation and transfer from operating room and upon arrival at the ward
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End point type |
Secondary
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End point timeframe |
12 h
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Notes [3] - 2 pre-intervention exclusion [4] - 1 pre-intervention exclusion |
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Statistical analysis title |
discharge scores | |||||||||||||||||||||
Comparison groups |
Dexamethasone 8 mg v Dexamethasone 24 mg
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Number of subjects included in analysis |
127
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.114 [5] | |||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||||||||
Confidence interval |
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Notes [5] - at transfer 0.294, ward 0.076 |
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End point title |
Pain scores | |||||||||||||||||||||
End point description |
Pain scores at extubation, transfer from the operating room and arrival at ward
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End point type |
Secondary
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End point timeframe |
12 h
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Notes [6] - 2 pre-intervention exclusion [7] - 1 pre-intervention exclusion |
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Statistical analysis title |
pain scores | |||||||||||||||||||||
Comparison groups |
Dexamethasone 8 mg v Dexamethasone 24 mg
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Number of subjects included in analysis |
127
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.009 [8] | |||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Confidence interval |
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Notes [8] - at transfer 0.416, arrival at ward 0.097 |
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End point title |
Lenght of stay | ||||||||||||||||||
End point description |
lenght of stay, measured from start of operation to discharge from hospital (hospital), or end of operation to discharge from PACU (PACU)
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End point type |
Secondary
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End point timeframe |
30 days
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Notes [9] - 2 pre-intervention exclusion [10] - 1 pre-intervention exclusion |
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Statistical analysis title |
LOS | ||||||||||||||||||
Comparison groups |
Dexamethasone 8 mg v Dexamethasone 24 mg
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Number of subjects included in analysis |
127
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.217 [11] | ||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||
Confidence interval |
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Notes [11] - PACU 0.350 |
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End point title |
Readmission | |||||||||
End point description |
any readmission (other than scheduled oncological)
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End point type |
Secondary
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End point timeframe |
30 days
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Notes [12] - 2 pre-intervention exclusion [13] - 2 pre-intervention exclusion |
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Statistical analysis title |
readmissions | |||||||||
Comparison groups |
Dexamethasone 8 mg v Dexamethasone 24 mg
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Number of subjects included in analysis |
127
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.97 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.02
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.243 | |||||||||
upper limit |
4.3 |
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End point title |
Seroma | |||||||||
End point description |
no of patients with seroma requiring drainage
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End point type |
Secondary
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End point timeframe |
14 days
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Notes [14] - 2 pre-intervention exclusion [15] - 1 pre-intervention exclusion |
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Statistical analysis title |
seroma | |||||||||
Comparison groups |
Dexamethasone 8 mg v Dexamethasone 24 mg
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Number of subjects included in analysis |
127
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.03 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
3.53
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
1.07 | |||||||||
upper limit |
11.6 |
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End point title |
wound infection | |||||||||
End point description |
no of patients with wound infection req treatment
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End point type |
Secondary
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End point timeframe |
30 days
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Notes [16] - 2 pre-intervention exclusion [17] - 1 pre-intervention exclusion |
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Statistical analysis title |
wound infection | |||||||||
Comparison groups |
Dexamethasone 8 mg v Dexamethasone 24 mg
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Number of subjects included in analysis |
127
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.315 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.33
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.03 | |||||||||
upper limit |
3.24 |
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End point title |
Proportion of patients actually transferred | |||||||||
End point description |
Post-hoc analysis of patients actually transferred to PACU, since not all patients who met the criteria for transfer were actually transferred
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End point type |
Post-hoc
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End point timeframe |
1 h
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Notes [18] - 2 pre-intervention exclusion [19] - 1 pre-intervention exclusion |
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Statistical analysis title |
post hoc primary endpoint | |||||||||
Comparison groups |
Dexamethasone 8 mg v Dexamethasone 24 mg
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Number of subjects included in analysis |
127
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Analysis specification |
Post-hoc
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Analysis type |
superiority | |||||||||
P-value |
> 0.999 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.41 | |||||||||
upper limit |
2.43 |
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Adverse events information
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Timeframe for reporting adverse events |
60 hours from intervention administration
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Adverse event reporting additional description |
Patient charts, patient questionnaire
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
SNOMED CT | |||||||||||||||||||||||||||||||||
Dictionary version |
2019-09-30
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Reporting groups
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Reporting group title |
Dexamethasone 8 mg
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Reporting group description |
Single-shot preoperative injection | |||||||||||||||||||||||||||||||||
Reporting group title |
Dexamethasone 24 mg
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Reporting group description |
Single shot pre-operative injection, 24 mg | |||||||||||||||||||||||||||||||||
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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? 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 |