Clinical Trial Results:
Spinal fentanyl or epidural analgesia in the early first phase of induced labor
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Summary
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EudraCT number |
2020-005506-26 |
Trial protocol |
FI |
Global end of trial date |
18 May 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Sep 2023
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First version publication date |
13 Sep 2023
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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 |
Versio4
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04645823 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
HUCH/Women's hospital
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Sponsor organisation address |
Haartmaninkatu 2, Helsinki, Finland, 00029
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Public contact |
department of Anaesthesia, HUCH/Women's hospital, 358 504271850, antti.vaananen@hus.fi
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Scientific contact |
department of Anaesthesia, HUCH/Women's hospital, 358 504271850, antti.vaananen@hus.fi
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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 |
31 Jul 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 May 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
18 May 2023
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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 compare analgesia achieved in 30 minutes by spinal fentanyl with analgesia by epidural lidocaine and fentanyl
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Protection of trial subjects |
The participants (the parturients undergoing labor) were monitored by the study personnel and the midwives at the labor ward. The fetal wellbeing was monitored by continuous cardiotocography and the maternal neurological status and blood pressure was directly monitored by the care staff. The efficacy of analgesia (outcome of the trial) was monitored by the study personnel and the labor pain was treated as needed after the trial. The parturients' were checked for potential long term adverse effects after the delivery and lack of side effects was checked 30 days after the delivery from the patient files.
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Background therapy |
Normal care for parturients undergoing induction of labor, including analgesics paracetamol per orally or intramuscular opioids (oxycodone) if needed. | ||
Evidence for comparator |
The active comparator (intrathecal fentanyl) has been shown to be effective in alleviating labor pain and is routinely used for over 30 % of the parturients outside this study in our hospital district's hospitals (the treatment is used for approximately 4000 deliveries per year). | ||
Actual start date of recruitment |
01 Feb 2021
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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 |
Finland: 60
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Worldwide total number of subjects |
60
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EEA total number of subjects |
60
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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) |
60
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The parturients who were coming for the induction of labor were informed about the study in both oral and written form at the early phase of the induction. Those who agreed to participate were randomized to either group when they requested neuraxial analgesia for labor. | |||||||||
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Pre-assignment
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Screening details |
The parturients were to have induced labor for their first attempted vaginal delivery. They were to have not contraindications for either intervention and they were to have BMI of 20-40 and a singleton pregnancy. The screening was done before the parturients had significant contraction pain. | |||||||||
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Period 1
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Period 1 title |
Onset of analgesia
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Is this the baseline period? |
No | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Investigator, Carer, Assessor, Subject | |||||||||
Blinding implementation details |
The anesthesiologist who completed the analgesic intervention was not blinded. (S)he exited the labor suite after the analgesic intervention and the study investigator entered the room to the monitor the parturient unaware of the intervention. The midwife and the parturient present in the room were not informed about the intervention given.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Epidural analgesia | |||||||||
Arm description |
A combination of lidocaine 80 mg and fentanyl citrate 100 micrograms given epidurally | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Lidocain Claris 10 mg/ml
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Investigational medicinal product code |
PR2
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Epidural use
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Dosage and administration details |
8 millilitres of the 10 mg/ml solution is mixed with 2 ml of fentanyl citrate (PR3) and given epidurally
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Investigational medicinal product name |
Fentenyl hameln (50 microgram /ml)
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Investigational medicinal product code |
PR3
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Epidural use
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Dosage and administration details |
2 ml of fentanyl citrate (PR3) is mixed with 8 ml of lidocain 10 mg/ml (PR2) and given epidurally
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Arm title
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Intrathecal fentanyl | |||||||||
Arm description |
A dose of 20 migrograms of fentanyl citrate is given intrathecally in a total volume of 2 ml (dilution with sterile saline) | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Fentenyl hameln (50 microgram /ml)
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Investigational medicinal product code |
PR1
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intrathecal use
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Dosage and administration details |
0,4 ml (20 micrograms) is diluted with sterile saline to a volume of 2 ml and given intrathecally
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Period 2
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Period 2 title |
duration of analgesia
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Is this the baseline period? |
No | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Carer, Assessor, Subject, Investigator | |||||||||
Blinding implementation details |
Neither the parturient, the midwife or the assessor in the labor room were aware of the intervention given to the parturient
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Epidural analgesia | |||||||||
Arm description |
A combination of lidocaine 80 mg and fentanyl citrate 100 micrograms given epidurally | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Lidocain Claris 10 mg/ml
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Investigational medicinal product code |
PR2
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Epidural use
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Dosage and administration details |
8 millilitres of the 10 mg/ml solution is mixed with 2 ml of fentanyl citrate (PR3) and given epidurally
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Investigational medicinal product name |
Fentenyl hameln (50 microgram /ml)
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Investigational medicinal product code |
PR3
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Epidural use
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Dosage and administration details |
2 ml of fentanyl citrate (PR3) is mixed with 8 ml of lidocain 10 mg/ml (PR2) and given epidurally
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Arm title
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Intrathecal fentanyl | |||||||||
Arm description |
A dose of 20 migrograms of fentanyl citrate is given intrathecally in a total volume of 2 ml (dilution with sterile saline) | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Fentenyl hameln (50 microgram /ml)
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Investigational medicinal product code |
PR1
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intrathecal use
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Dosage and administration details |
0,4 ml (20 micrograms) is diluted with sterile saline to a volume of 2 ml and given intrathecally
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Period 3
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Period 3 title |
Pre analgesia
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Is this the baseline period? |
Yes [1] | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
The allocation to either groups was done by opening a consequtively numbered sealed non-tranparent envelope at the time of request for neuraxial analgesia. At baseline no allocation was made yet.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Epidural analgesia | |||||||||
Arm description |
A combination of lidocaine 80 mg and fentanyl citrate 100 micrograms given epidurally | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Lidocain Claris 10 mg/ml
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Investigational medicinal product code |
PR2
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Epidural use
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Dosage and administration details |
8 millilitres of the 10 mg/ml solution is mixed with 2 ml of fentanyl citrate (PR3) and given epidurally
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Investigational medicinal product name |
Fentenyl hameln (50 microgram /ml)
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Investigational medicinal product code |
PR3
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Epidural use
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Dosage and administration details |
2 ml of fentanyl citrate (PR3) is mixed with 8 ml of lidocain 10 mg/ml (PR2) and given epidurally
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Arm title
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Intrathecal fentanyl | |||||||||
Arm description |
A dose of 20 migrograms of fentanyl citrate is given intrathecally in a total volume of 2 ml (dilution with sterile saline) | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Fentenyl hameln (50 microgram /ml)
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Investigational medicinal product code |
PR1
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intrathecal use
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Dosage and administration details |
0,4 ml (20 micrograms) is diluted with sterile saline to a volume of 2 ml and given intrathecally
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| Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: The "pre analgesia" - period (period 3) IS the baseline period. |
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Baseline characteristics reporting groups
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Reporting group title |
Pre analgesia
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Reporting group description |
The parturients at the time of receiving their neuraxial analgesia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Baseline
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The baseline characterists at the time of intervention
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End points reporting groups
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Reporting group title |
Epidural analgesia
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Reporting group description |
A combination of lidocaine 80 mg and fentanyl citrate 100 micrograms given epidurally | ||
Reporting group title |
Intrathecal fentanyl
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Reporting group description |
A dose of 20 migrograms of fentanyl citrate is given intrathecally in a total volume of 2 ml (dilution with sterile saline) | ||
Reporting group title |
Epidural analgesia
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Reporting group description |
A combination of lidocaine 80 mg and fentanyl citrate 100 micrograms given epidurally | ||
Reporting group title |
Intrathecal fentanyl
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Reporting group description |
A dose of 20 migrograms of fentanyl citrate is given intrathecally in a total volume of 2 ml (dilution with sterile saline) | ||
Reporting group title |
Epidural analgesia
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Reporting group description |
A combination of lidocaine 80 mg and fentanyl citrate 100 micrograms given epidurally | ||
Reporting group title |
Intrathecal fentanyl
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Reporting group description |
A dose of 20 migrograms of fentanyl citrate is given intrathecally in a total volume of 2 ml (dilution with sterile saline) | ||
Subject analysis set title |
Baseline
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The baseline characterists at the time of intervention
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End point title |
Pain during contraction at 30 minutes | ||||||||||||
End point description |
The maximum pain during contraction at 30 minutes after the intervention
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End point type |
Primary
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End point timeframe |
30 minutes
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Statistical analysis title |
Pain during the contraction at 30 minutes | ||||||||||||
Statistical analysis description |
Comparison between the treatment groups for maximum pain during contraction at 30 minutes after the analgesic intervention
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Comparison groups |
Epidural analgesia v Intrathecal fentanyl
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Number of subjects included in analysis |
60
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [1] | ||||||||||||
P-value |
= 0.677 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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| Notes [1] - The study aimed for equal analgesia |
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End point title |
Pain at 20 minutes | ||||||||||||
End point description |
pain at 20 minutes after the intervention
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End point type |
Secondary
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End point timeframe |
20 minutes
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Statistical analysis title |
PAin during contraction 20 minutes | ||||||||||||
Statistical analysis description |
The maximum pain during contraction 20 minutes after the analgesic intervention
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Comparison groups |
Epidural analgesia v Intrathecal fentanyl
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Number of subjects included in analysis |
60
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [2] | ||||||||||||
P-value |
= 0.661 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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| Notes [2] - The study aimed for equal analgesia |
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End point title |
Duration of analgesia | ||||||||||||
End point description |
The time until the parturient receives the first epidural analgesia dose after the study analgesic intervention marking the duration of action of the studied intervention
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End point type |
Secondary
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End point timeframe |
0-180 minutes
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Statistical analysis title |
Duration of analgesia | ||||||||||||
Statistical analysis description |
in minutes between the two treatment arms
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Comparison groups |
Epidural analgesia v Intrathecal fentanyl
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Number of subjects included in analysis |
60
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.36 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Maternal satisfaction with analgesia at 30 min | ||||||||||||
End point description |
The parturients assessment of the satisfaction with the analgesia on a 100 mm visual analog scale (0=completely dissatisfied; 100= completely satisfied)
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End point type |
Secondary
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End point timeframe |
30 minutes
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Statistical analysis title |
Maternal satisfaction | ||||||||||||
Statistical analysis description |
Non parametric test for maternal satisfaction scores
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Comparison groups |
Epidural analgesia v Intrathecal fentanyl
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Number of subjects included in analysis |
60
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.486 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
180 minutes
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Adverse event reporting additional description |
The parturients were followed for the potential adverse events for upto 180 minutes
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
SNOMED CT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Epidural analgesia
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Reporting group description |
The groups of parturients that received epidural analgesia (80 mg lidocaine 1 % and fentanyl citrate 100 micrograms) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Intrathecal fentanyl
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Reporting group description |
The group of parturients that received intrathecal fentanyl (20 micrograms) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 3% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 | |||
