Clinical trial NCT02179294: A Randomised Controlled Trial of Remifentanil Intravenous Patient Controlled Analgesia (PCA) Versus Intramuscular Pethidine for Pain Relief in Labour
Official title: A Randomised Controlled Trial of Remifentanil Intravenous Patient Controlled Analgesia (PCA) Versus Intramuscular Pethidine for Pain Relief in Labour
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain Relief in Labour
Keywords: Pain relief
Labour
Child birth
Anaesthetics
Lead sponsor: University of Birmingham
Sponsor class: OTHER
Collaborators: name: Heartlands Hospital
name: Good Hope Hospital
name: Birmingham Women's NHS Foundation Trust
name: York Hospital
name: University Hospital of North Midlands
name: Frimley Park Hospital
name: Bradford Royal Infirmary
name: Stoke Mandeville Hospital
name: Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
name: Medway Maritime Hospital
name: Northwick Park Hospital
name: Homerton University Hospital
name: City Hospital Birmingham
name: Warwick Hospital
name: University Hospital Coventry
First posted: 2014-07-01
Enrollment: 401
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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).

Primary outcomes:
measure: The proportion of women who receive epidural analgesia for pain relief in labour, in each group, after randomisation.
timeFrame: At labour
Secondary outcomes:
measure: • The effectiveness of pain relief provided by each technique, quantified by Visual Analogue Scale
timeFrame: Post natally - Average of 2-3days after delivery
measure: The incidence of maternal side effects
timeFrame: Post Natally - Average of 2-3days after delivery
measure: Delivery mode (Spontaneous, Instrumental Vaginal, Caesarean Section)
timeFrame: Post Natally - Average of 2-3days after delivery
measure: Incidence of foetal distress requiring delivery
timeFrame: Post Natally - Average of 2-3days after delivery
measure: Neonatal status at delivery
timeFrame: Post Natally - Average of 2-3days after delivery
measure: Rate of initiation of breast feeding within the first hour of birth
timeFrame: Post Natally - 1 hour after delivery
measure: Maternal satisfaction with childbirth experience determined by postpartum questionnaire prior to discharge from the delivery ward
timeFrame: Post Natally - Average of 2-3days after delivery
measure: Maternal birth experience determined by qualitative telephone interview up to six weeks postpartum
timeFrame: Up to 6 weeks post-partum
measure: Maternal perceptions of pain relief determined by qualitative telephone interview up to six weeks postpartum
timeFrame: Up to 6 weeks post-partum
measure: Infant feeding behaviours determined by qualitative telephone interview up to six weeks postpartum
timeFrame: Up to 6 weeks post-partum
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Clinical Trials Unit
state: West Midlands
Study officials:
affiliation: Sheffield Teaching Hospitals NHS Foundation Trust
name: Matthew JA Wilson
role: PRINCIPAL_INVESTIGATOR
References: