Clinical Trial Results:
Effect of Perineural Dexamethasone on the Duration of Single Injection Saphenous Nerve Block for Analgesia After Major Ankle Surgery
Summary
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EudraCT number |
2014-004207-78 |
Trial protocol |
DK |
Global end of trial date |
16 Dec 2015
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Results information
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Results version number |
v2(current) |
This version publication date |
25 Jan 2021
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First version publication date |
16 Jul 2017
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Other versions |
v1 |
Version creation reason |
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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 |
ProtokolSB1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02346110 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Aarhus University Hospital
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Sponsor organisation address |
Nørrebrogade 44, Aarhus C, Denmark, 8000
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Public contact |
Department of Anesthesia and Intensive Care, Aarhus University Hospital, +45 51542997, tfb@dadlnet.dk
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Scientific contact |
Department of Anesthesia and Intensive Care
, Aarhus University Hospital, +45 51542997, tfb@dadlnet.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 |
29 Mar 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Dec 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Dec 2015
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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 |
The main objective is to investigate whether addition of the adjuvant
dexamethasone to bupivacaine-adrenaline can prolong the analgesic
effect of the saphenous block compared to plain bupivacaine-adrenaline
in patients after major ankle and hind foot surgery.
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Protection of trial subjects |
Patients received a PCA pump with morphine to provide instant pain relief at bolus request. Patients were visited at regular intervals during the observation period with extra focus on their pain management.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Apr 2015
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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 |
Denmark: 39
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Worldwide total number of subjects |
39
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EEA total number of subjects |
39
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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) |
25
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From 65 to 84 years |
14
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were enrolled from 27/Apr/2015 - 14/Dec/2015. | |||||||||
Pre-assignment
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Screening details |
62 patients were screened. Reasons for primary exclusion: Operation type not included (n = 5) Logistical reasons ( n = 6) Operation cancelled/rescheduled (n = 4) Daily intake of strong opioids (n = 2) Allergy to opioids (n = 1) Communication problems (n = 1) BMI > 35 (n = 2) Neuropathy (n = 1) | |||||||||
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, Assessor | |||||||||
Blinding implementation details |
The hospital pharmacy performed the randomization in blocks of 10 and a 1:1 ratio, and prepared 40 consecutively numbered black nontransparent plastic bags containing 1 mL of saline or 1 mL of dexamethasone according to the randomization list. Isotonic saline and dexamethasone are both transparent liquids, all containers and bags were identical.
One patient was excluded due to incorrect inclusion (communication problems) this patient is not included in any data analysis.
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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 |
Saphenous block with 10 mL Marcain-adrenalin + 1 ml (4 mg) Dexamethasone. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Dexamethason
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Investigational medicinal product code |
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Other name |
Dexagalen
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Perineural use
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Dosage and administration details |
4 mg
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Investigational medicinal product name |
Marcain-adrenalin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Perineural use
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Dosage and administration details |
10 mL Marcain-adrenalin containing:
BUPIVACAINE HYDROCHLORIDE 5 mg/ml milligram
EPINEPHRINE 5 μg/ml
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Arm title
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Control group | |||||||||
Arm description |
Saphenous block with 10 mL Marcain-adrenalin + 1 mL saline | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Marcain-adrenalin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Perineural use
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Dosage and administration details |
10 mL Marcain-adrenalin containing:
BUPIVACAINE HYDROCHLORIDE 5 mg/ml
EOINEOHRINE 5 μg/ml
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Baseline characteristics reporting groups
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Reporting group title |
Intervention
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Reporting group description |
Saphenous block with 10 mL Marcain-adrenalin + 1 ml (4 mg) Dexamethasone. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
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Reporting group description |
Saphenous block with 10 mL Marcain-adrenalin + 1 mL saline | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Intervention
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Reporting group description |
Saphenous block with 10 mL Marcain-adrenalin + 1 ml (4 mg) Dexamethasone. | ||
Reporting group title |
Control group
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Reporting group description |
Saphenous block with 10 mL Marcain-adrenalin + 1 mL saline |
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End point title |
Time until first opioid request | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
0-48 hrs
Time zero = end of saphenous block performance
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Statistical analysis title |
Time until first opioid request | ||||||||||||
Comparison groups |
Control group v Intervention
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.048 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
6.2
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.1 | ||||||||||||
upper limit |
12.3 |
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End point title |
Time until first pain | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
0-48 hrs
Time zero = End of saphenous block performance
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Statistical analysis title |
Time until first pain | ||||||||||||
Statistical analysis description |
T-test
Normally distributed data
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Comparison groups |
Intervention v Control group
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.026 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
6.8
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.9 | ||||||||||||
upper limit |
12.7 |
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End point title |
Opioid consumption 0-24 hrs | ||||||||||||
End point description |
The opioid consumption was not normally distributed
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End point type |
Secondary
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End point timeframe |
0-24 hours
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Statistical analysis title |
Opioid consumption 0-24 hrs | ||||||||||||
Comparison groups |
Intervention v Control group
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
= 0.046 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [1] - Opioid consumption was not normally distributed. |
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End point title |
Opioid consumption 24-48 hrs | ||||||||||||
End point description |
The opioid consumption was not normally distributed
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End point type |
Secondary
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End point timeframe |
24-48 hrs
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Statistical analysis title |
Opioid consumption 24-48 hrs | ||||||||||||
Comparison groups |
Intervention v Control group
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.989 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were reported from inclusion of the first patient 27/Apr/2015 and until the last patient completed the study observation period 16/Dec/2015.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||
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
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Reporting group description |
Saphenous block with 10 mL Marcain-adrenalin + 1 ml (4 mg) Dexamethasone. | |||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
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Reporting group description |
Saphenous block with 10 mL Marcain-adrenalin + 1 mL saline | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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25 Apr 2015 |
Changes:
Sensory testing at the 42 hour test time is deleted
Pain score at 42 the hour test time is deleted
Sensory testing and pain score at 42 hours are deleted because this time point consistently is in the middle of the night, and it is difficult to wake up the patients and get valid test results. Furthermore, as most of the patients will be sleeping we find it more ethical to let the patients sleep through the night.
Ankle arthrodesis performed as an arthroscopy is removed as an exclusion criteria. |
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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. | |||
Five patients did not require opioids at all. These patients contribute to the primary outcome with the time until a shift in sensory thermanalgesia in the infrapatellar area. This was chosen as the best proxy marker for the end of block duration. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/28033159 |