Pain Relief in LabourPhase 4RESPITENCT02179294
A Randomised Controlled Trial of Remifentanil Intravenous Patient Controlled Analgesia (PCA) Versus Intramuscular Pethidine for Pain Relief in Labour
A Phase 4 study testing Pethidine and Remifentanil in people with Pain Relief in Labour, run by University of Birmingham at 1 site in United Kingdom.
Trial summary
Childbirth can be an extremely painful and the provision of pain relief during labour is a vital component of a positive maternal experience. The majority of women who deliver in modern obstetric units choose a pharmacological method of pain relief, including Entonox, the injection of opioids or epidural placement. Read more about this study
- Who is it for?
- Ages 16 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pain Relief in Labour
- What is being tested?
- Pethidine and Remifentanil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 401 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2014to Sep 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Women who are admitted to labour ward who fulfil all the following criteria will be eligible to be randomised:
- Requesting systemic opioid analgesia
- 16 years of age or older
- Beyond 37 weeks gestation
- In established labour, defined as regular painful contractions, irrespective of cervical dilatation, with vaginal birth intended
- Able to understand all information (written and oral) presented (using an interpreter if necessary)
- Not participating in any other clinical trial of a medicinal product
- Live, singleton pregnancy with cephalic presentation
Who cannot join
- Contraindication to epidural analgesia
- Contraindication to intramuscular injection
- History of a previous adverse reaction to pethidine or remifentanil
- Patients taking long term opioid therapy including Methadone
- Systemic pain relief opioid in the last 4 hours administered by intravenous or intramuscular injection. (Oral medications comprising opioids alone or in combination preparations, administered in this 4 hour period, are permitted).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Birmingham Clinical Trials Unit
Birmingham, West Midlands, B15 2TT
About this study
Childbirth can be an extremely painful and the provision of pain relief during labour is a vital component of a positive maternal experience. The majority of women who deliver in modern obstetric units choose a pharmacological method of pain relief, including Entonox, the injection of opioids or epidural placement. The commonest opioid used in labour is pethidine administered by intramuscular (im) injection. The effectiveness of pain relief provided by pethidine has long been challenged. Its shortcomings are more serious when set against known side effects including maternal sedation, nausea and potential transfer across the placenta to the foetus. More than a third of women who receive pethidine subsequently require an epidural due to inadequate pain relief. Epidurals provide highly effective pain relief, but increase the risk of a forceps or suction delivery resulting in prolonged hospital stay. Therefore, there is a clear need for a safe, effective, easy to administer analgesic alternative.
Read the detailed description
Patient Controlled Analgesia (PCA) comprises drug administration into an intravenous drip with a small dose given each time a woman presses a button, giving her control over her own pain relief. The pump is programmed to ensure that the maximum dose allowable is within the safe range. This form of delivery of pain relief matches the drug dose to pain sensation within the relevant time frame, which is not possible using a single dose intramuscular injection. Whilst PCA is in widespread use for acute pain relief it has only a limited role in obstetrics. The most common drug given by PCA is morphine, however, since it has a long duration of action and crosses the placenta, the potential for accumulation in the foetus and consequent neonatal sedation at delivery restricts its utility (within obstetrics) to contexts where neonatal status is not relevant, such as intra-uterine foetal death or foetal abnormality incompatible with survival.
Remifentanil is a novel synthetic opioid with a very rapid onset (blood-brain equilibration 1.2-1.4 minutes) and short duration of action (context specific half-life 3 minutes), giving it an analgesic profile which potentially makes it ideal for providing pain relief over 1-2 uterine contractions after a single intravenous dose. It is subject to rapid redistribution and metabolism by non-specific blood and tissue esterases negating the potential for accumulation in mother or foetus. Administration of remifentanil by PCA has been investigated in several small studies in comparison to pethidine and shown to provide useful, although not complete, pain relief in labour.10-12 Thus far, there is no evidence of detrimental neonatal effects in comparison to other opioids.
- Conditions
- Pain Relief in Labour
- Being tested
- Pethidine, Remifentanil
- Keywords
- Pain relief, Labour, Child birth, Anaesthetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PethidineDrug
Also called Meperidine
100mg by intramuscular injection, up to 4 hourly in frequency (up to a maximum of 4 doses). The maximum dose being 400mg in 24 hours.
RemifentanilDrug
Also called Ultiva
Dedicated intravenous cannula for remifentanil administration PCA protocol
- PCA bolus remifentanil 40 μg
- Lockout interval 2 minutes
In the event of excess sedation being recorded by regular observation of respiratory function, the regimen will be altered by reduction of the remifentanil bolus dose to 30 μg with a lock-out interval of 2 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Pethidine | Active comparator | Pethidine is pain relief in labour Receives: Drug: Pethidine |
| Remifentanil | Active comparator | Remifentanil intravenous patient controlled analgesia Receives: Drug: Remifentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of women who receive epidural analgesia for pain relief in labour, in each group, after randomisation.
The proportion of women who receive epidural analgesia for pain relief in labour, in each group, after randomization.
Measured: At labour
Secondary outcomes (10)
• The effectiveness of pain relief provided by each technique, quantified by Visual Analogue Scale
- The effectiveness of pain relief provided by each technique, quantified by Visual Analogue Scale
Measured: Post natally - Average of 2-3days after delivery
The incidence of maternal side effects
The incidence of maternal side effects including
- Excessive sedation score
- Oxygen Saturation <94% whilst breathing room air
- Nausea requiring anti-emetic administration
- Requirement and indication for supplemental oxygen
- Respiratory Depression (Respiratory rate < 8 breaths/minute)
Measured: Post Natally - Average of 2-3days after delivery
Delivery mode (Spontaneous, Instrumental Vaginal, Caesarean Section)
Delivery mode (Spontaneous, Instrumental Vaginal, Caesarean Section)
Measured: Post Natally - Average of 2-3days after delivery
Incidence of foetal distress requiring delivery
Incidence of foetal distress requiring delivery
Measured: Post Natally - Average of 2-3days after delivery
Neonatal status at delivery
Neonatal status at delivery:
- Apgar score at 5 minutes
- Incidence of foetal acidosis determined by umbilical cord gas analysis
- Requirement for neonatal resuscitation
- Incidence of and indication for admission to neonatal care
Measured: Post Natally - Average of 2-3days after delivery
Rate of initiation of breast feeding within the first hour of birth
Rate of initiation of breast feeding within the first hour of birth
Measured: Post Natally - 1 hour after delivery
Maternal satisfaction with childbirth experience determined by postpartum questionnaire prior to discharge from the delivery ward
Maternal satisfaction with childbirth experience determined by postpartum questionnaire prior to discharge from the delivery ward
Measured: Post Natally - Average of 2-3days after delivery
Maternal birth experience determined by qualitative telephone interview up to six weeks postpartum
Explore and compare women's birth experiences up to six weeks postpartum via qualitative telephone interview (Post-Natal sub-study)
Measured: Up to 6 weeks post-partum
Maternal perceptions of pain relief determined by qualitative telephone interview up to six weeks postpartum
Explore and compare women's perceptions of pain relief up to six weeks postpartum via qualitative telephone interview (Post-Natal sub-study)
Measured: Up to 6 weeks post-partum
Infant feeding behaviours determined by qualitative telephone interview up to six weeks postpartum
Explore and compare infant feeding behaviours up to six weeks postpartum via qualitative telephone interview (Post-Natal sub-study)
Measured: Up to 6 weeks post-partum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2014 (estimated)
- Study startMay 2014
- Primary completionSep 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pain Relief in LabourStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 401 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Heartlands Hospital, Good Hope Hospital, Birmingham Women's NHS Foundation Trust, York Hospital, University Hospital of North Midlands, Frimley Park Hospital, Bradford Royal Infirmary, Stoke Mandeville Hospital, Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK), Medway Maritime Hospital, Northwick Park Hospital, Homerton University Hospital, City Hospital Birmingham, Warwick Hospital, University Hospital Coventry
- Responsible party
- Sponsor
- Investigators
- Matthew JA Wilson, Principal investigator, Sheffield Teaching Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02179294
- Sponsor's protocol ID
- RG_12-151
- Other IDs
- 2012-005257-22
- Acronym
- RESPITE
- Status last verified
- Oct 2018
- First submitted
- 11 Jun 2014
- Last updated
- 15 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial of Remifentanil Intravenous Patient Controlled Analgesia (PCA) Versus Intramuscular Pethidine for Pain Relief in Labour
- ClinicalTrials.gov ID
- NCT02179294
- Acronym / sponsor ID
- RESPITE / RG_12-151
- Conditions
- Pain Relief in Labour
- Keywords
- Pain relief, Labour, Child birth, Anaesthetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 401 participants (actual)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- Heartlands Hospital, Good Hope Hospital, Birmingham Women's NHS Foundation Trust, York Hospital, University Hospital of North Midlands, Frimley Park Hospital, Bradford Royal Infirmary, Stoke Mandeville Hospital, Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK), Medway Maritime Hospital, Northwick Park Hospital, Homerton University Hospital, City Hospital Birmingham, Warwick Hospital, University Hospital Coventry
- Study start
- May 2014
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 1 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Childbirth can be an extremely painful and the provision of pain relief during labour is a vital component of a positive maternal experience. The majority of women who deliver in modern obstetric units choose a pharmacological method of pain relief, including Entonox, the injection of opioids or epidural placement. The commonest opioid used in labour is pethidine administered by intramuscular (im) injection. The effectiveness of pain relief provided by pethidine has long been challenged. Its shortcomings are more serious when set against known side effects including maternal sedation, nausea and potential transfer across the placenta to the foetus. More than a third of women who receive pethidine subsequently require an epidural due to inadequate pain relief. Epidurals provide highly effective pain relief, but increase the risk of a forceps or suction delivery resulting in prolonged hospital stay. Therefore, there is a clear need for a safe, effective, easy to administer analgesic alternative.
Detailed description
Patient Controlled Analgesia (PCA) comprises drug administration into an intravenous drip with a small dose given each time a woman presses a button, giving her control over her own pain relief. The pump is programmed to ensure that the maximum dose allowable is within the safe range. This form of delivery of pain relief matches the drug dose to pain sensation within the relevant time frame, which is not possible using a single dose intramuscular injection. Whilst PCA is in widespread use for acute pain relief it has only a limited role in obstetrics. The most common drug given by PCA is morphine, however, since it has a long duration of action and crosses the placenta, the potential for accumulation in the foetus and consequent neonatal sedation at delivery restricts its utility (within obstetrics) to contexts where neonatal status is not relevant, such as intra-uterine foetal death or foetal abnormality incompatible with survival.
Remifentanil is a novel synthetic opioid with a very rapid onset (blood-brain equilibration 1.2-1.4 minutes) and short duration of action (context specific half-life 3 minutes), giving it an analgesic profile which potentially makes it ideal for providing pain relief over 1-2 uterine contractions after a single intravenous dose. It is subject to rapid redistribution and metabolism by non-specific blood and tissue esterases negating the potential for accumulation in mother or foetus. Administration of remifentanil by PCA has been investigated in several small studies in comparison to pethidine and shown to provide useful, although not complete, pain relief in labour.10-12 Thus far, there is no evidence of detrimental neonatal effects in comparison to other opioids.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pethidine | Active comparator | Drug: PethidinePethidine is pain relief in labour |
| Remifentanil | Active comparator | Drug: RemifentanilRemifentanil intravenous patient controlled analgesia |
Who may qualify
- Ages
- 16 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Women who are admitted to labour ward who fulfil all the following criteria will be eligible to be randomised:
- Requesting systemic opioid analgesia
- 16 years of age or older
- Beyond 37 weeks gestation
- In established labour, defined as regular painful contractions, irrespective of cervical dilatation, with vaginal birth intended
Key exclusion criteria (5 listed)
- Contraindication to epidural analgesia
- Contraindication to intramuscular injection
- History of a previous adverse reaction to pethidine or remifentanil
- Patients taking long term opioid therapy including Methadone
- Systemic pain relief opioid in the last 4 hours administered by intravenous or intramuscular injection. (Oral medications comprising opioids alone or in combination preparations, administered in this 4 hour period, are permitted).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PethidineAlso: Meperidine100mg by intramuscular injection, up to 4 hourly in frequency (up to a maximum of 4 doses). The maximum dose being 400mg in 24 hours. | Drug | Pethidine |
| RemifentanilAlso: UltivaDedicated intravenous cannula for remifentanil administration PCA protocol * PCA bolus remifentanil 40 μg * Lockout interval 2 minutes In the event of excess sedation being recorded by regular observation of respiratory function, the regimen will be altered by reduction of the remifentanil bolus dose to 30 μg with a lock-out interval of 2 minutes. | Drug | Remifentanil |
Primary outcome
The proportion of women who receive epidural analgesia for pain relief in labour, in each group, after randomisation.
Time frame: At labour
The proportion of women who receive epidural analgesia for pain relief in labour, in each group, after randomization.
10 secondary outcomes
• The effectiveness of pain relief provided by each technique, quantified by Visual Analogue Scale
Time frame: Post natally - Average of 2-3days after delivery
The incidence of maternal side effects
Time frame: Post Natally - Average of 2-3days after delivery
Delivery mode (Spontaneous, Instrumental Vaginal, Caesarean Section)
Time frame: Post Natally - Average of 2-3days after delivery
Incidence of foetal distress requiring delivery
Time frame: Post Natally - Average of 2-3days after delivery
Neonatal status at delivery
Time frame: Post Natally - Average of 2-3days after delivery
Rate of initiation of breast feeding within the first hour of birth
Time frame: Post Natally - 1 hour after delivery
Maternal satisfaction with childbirth experience determined by postpartum questionnaire prior to discharge from the delivery ward
Time frame: Post Natally - Average of 2-3days after delivery
Maternal birth experience determined by qualitative telephone interview up to six weeks postpartum
Time frame: Up to 6 weeks post-partum
Maternal perceptions of pain relief determined by qualitative telephone interview up to six weeks postpartum
Time frame: Up to 6 weeks post-partum
Infant feeding behaviours determined by qualitative telephone interview up to six weeks postpartum
Time frame: Up to 6 weeks post-partum
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2018.
- Trial websiteLink provided by the sponsor.
Related trials for Pain Relief in Labour
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew JA Wilson principal investigator
Sheffield Teaching Hospitals NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pethidine and Remifentanil in people with Pain Relief in Labour, run by University of Birmingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of women who receive epidural analgesia for pain relief in labour, in each group, after randomisation. (time frame: At labour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2018.