Clinical Trial Results:
High volume PCEA versus PIEB for labor analgesia: a randomized, double-blind multicenter non-inferiority study in nulliparous women.
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Summary
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EudraCT number |
2019-003319-76 |
Trial protocol |
BE |
Global end of trial date |
10 Jan 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Sep 2022
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First version publication date |
29 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 |
MVDV/ER082019
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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 |
University Hospitals Leuven
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Sponsor organisation address |
Herestraat 48, Leuven, Belgium,
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Public contact |
Research Anesthesiology, University Hospitals Leuven, christel.huygens@uzleuven.be
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Scientific contact |
Research Anesthesiology, University Hospitals Leuven, christel.huygens@uzleuven.be
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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 |
10 Jan 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Jun 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Jan 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 |
The goal of our study was to compaire two techniques to maintain labour analgesia, Programmed intermittent epidural boluses (PIEB) plus patient controlled epidural analgesia (PCEA) and high volume PCEA without background infusion, on the incidence of breakthrough pain
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Protection of trial subjects |
There was a constant follow-up of the patient during labour when the maintenance epidural therapy was administered and there was an immediate management of breakthrough pain by adding a supplemental bolus of epidural analgesia to the patient.
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Background therapy |
Irrespective of group allocation, labour pain was initially treated with spinal administration of ropivacaine and sufentanil using a CSE (combined spinale epidural ) technique. An epidural catheter was inserted and the maintenance epidural therapy was started according to group assignment. | ||
Evidence for comparator |
PIEB has proven to be a very good maintenance therapy for labour analgesia and has been extensively compared to PCEA with background infusion. In these studies PIEB is superior to PCEA with background infusion. Bolus techniques have been proven to increase epidural spread compared to infusion techniques. A PCEA (bolus technique) without background infusion but with equal high-volume boluses has not been compared to PIEB. | ||
Actual start date of recruitment |
01 Oct 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 |
Belgium: 360
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Worldwide total number of subjects |
360
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EEA total number of subjects |
360
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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) |
360
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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 |
Between februari 1 2020 and June 30 2021 we screened 399 patients in UZLeuven and GZA St Augustinus of whom 360 were randomised | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Singleton, term pregnancies, ASA PS II, in active labour werre included. Patients were not recruited if : ASA III or IV, known allergies to the study drug, contra-indication for neuraxial analgesia, < 18 years old, cervical dilation >7, did not understand Dutch. | |||||||||||||||||||||
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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 |
Investigator, Monitor, Subject | |||||||||||||||||||||
Blinding implementation details |
Women were randomly allocated to the two study groups using a computer-generated block randomisation list (variable block-size with 1:1 allocation). Allocation concealment was achieved using opaque sealed envelopes containing group assignment, sequentially numbered. An anaesthetist not involved in patient management or data collection opened the envelope after oral and written informed consent and started the epidural maintenance regime according to the assigned group.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PCEA | |||||||||||||||||||||
Arm description |
After spinal administration of local anaesthetic analgesia, the maintenance pump was started in the PCEA (patient controlled epidural analgesia)-modus and labour analgesia was maintained using this PCEA-modus. | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Naropin
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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 |
Epidural use
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Dosage and administration details |
Naropin 0.12%
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Arm title
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PIEB | |||||||||||||||||||||
Arm description |
After spinal administration of local anaesthetic analgesia, the maintenance pump was started in the PIEB (programmed intermittent epidural bolus)-modus and labour analgesia was maintained using this PIEB-modus. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Naropin
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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 |
Epidural use
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Dosage and administration details |
Naropin 0.12%
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Baseline characteristics reporting groups
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Reporting group title |
PCEA
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Reporting group description |
After spinal administration of local anaesthetic analgesia, the maintenance pump was started in the PCEA (patient controlled epidural analgesia)-modus and labour analgesia was maintained using this PCEA-modus. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PIEB
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Reporting group description |
After spinal administration of local anaesthetic analgesia, the maintenance pump was started in the PIEB (programmed intermittent epidural bolus)-modus and labour analgesia was maintained using this PIEB-modus. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PCEA
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Reporting group description |
After spinal administration of local anaesthetic analgesia, the maintenance pump was started in the PCEA (patient controlled epidural analgesia)-modus and labour analgesia was maintained using this PCEA-modus. | ||
Reporting group title |
PIEB
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Reporting group description |
After spinal administration of local anaesthetic analgesia, the maintenance pump was started in the PIEB (programmed intermittent epidural bolus)-modus and labour analgesia was maintained using this PIEB-modus. | ||
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End point title |
Breakthrough pain | |||||||||
End point description |
A painscore of > 30 on a visual analogue scale
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End point type |
Primary
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End point timeframe |
The occurrence of breakthrough pain during labour
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Statistical analysis title |
Primary outcome | |||||||||
Comparison groups |
PCEA v PIEB
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Number of subjects included in analysis |
336
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | |||||||||
P-value |
≤ 0.05 | |||||||||
Method |
Farrington-Manning | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Point estimate |
0.1
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-7.03 | |||||||||
upper limit |
6.36 | |||||||||
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End point title |
local anesthetic consumption | |||||||||
End point description |
The amount of local anaesthetic solution used during labour
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End point type |
Secondary
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End point timeframe |
During labour
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Statistical analysis title |
Local anesthetic consumption | |||||||||
Comparison groups |
PCEA v PIEB
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Number of subjects included in analysis |
336
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
≤ 0.05 | |||||||||
Method |
independent t-test | |||||||||
Parameter type |
Median difference (final values) | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-19.6 | |||||||||
upper limit |
-4.7 | |||||||||
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End point title |
Satisfaction scores at 1 and 24 hours post-delivery | |||||||||
End point description |
A satisfaction score was asked at 1 hour (0-100) and 24 hours (0-10) after delivery of the baby
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End point type |
Secondary
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End point timeframe |
One hour after delivery and 24 hours after delivery satisfaction scores were recorded.
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Statistical analysis title |
Satisfaction scores at 1 and 24 hours | |||||||||
Comparison groups |
PCEA v PIEB
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Number of subjects included in analysis |
336
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
≤ 0.05 | |||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||
Parameter type |
Median difference (final values) | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.45 | |||||||||
upper limit |
0.55 | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
from enrollment untill the first 24 hours after delivery of the baby
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Adverse event reporting additional description |
Nausea/Vomiting, neurologic deficit, adverse neonatal outcome
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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 |
25
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Reporting groups
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Reporting group title |
PCEA
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Reporting group description |
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Reporting group title |
PIEB
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Reporting group description |
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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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02 Jun 2020 |
Change of PI and increase of inclusions after interim analysis |
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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. | |||
| None reported | |||
