Condition category
Pregnancy and Childbirth
Date applied
08/08/2013
Date assigned
08/08/2013
Last edited
21/12/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Childbirth can be a painful experience. Providing women with prompt pain relief is a priority for the midwives and doctors who care for them in labour. There are several forms of pain relief available to women, including gas-and-air (Entonox), strong pain relieving drugs, such as Pethidine and epidurals. Pethidine is the standard drug given in the UK, usually by injection into the thigh or arm. It is effective, but can cause side effects such as drowsiness and sickness. In recent years, some labour wards have begun to offer a different drug called Remifentanil for pain relief to some women. Remifentanil is given through a drip. By pressing a hand-held button, women give themselves a small dose of drug whilst having a contraction. Research done so far shows that Remifentinail is safe for women, and their babies, and provides effective pain relief. However, it is not yet offered as standard care. As with Pethidine, women can experience drowsiness and sickness. Epidurals provide excellent pain relief but can increase the chance of forceps or suction delivery. We do not know yet which of Remifentanil or Pethidine is better at helping women avoid the need for an epidural and experience a more straightforward birth. This study will find this out.

Who can participate?
Women at the participating hospitals who are expecting to have a vaginal birth and request pain relief will be considered for the study. We hope that 400 women will agree to take part.

What does the study involve?
If happy to take part in the study, women will be asked to sign a consent form. The person who takes consent will then enter their details into a computer. This will randomly allocate the woman to either the Pethidine or Remifentanil group. This decision will be made by chance, rather like the toss of a coin. This is important because it ensures that the two forms of pain relief can be tested fairly against each other. Information about the woman's labour will be then be collected by the midwife until they give birth and be kept confidentially. During labour, women will be asked how effective their pain relief is. We will record details of when the woman and baby are discharged from hospital, and details of any treatments received whilst in hospital. Participants will also be asked to fill in a short questionnaire to find out what they thought of the care they received during labour and the birth of the baby. There are no further tests or hospital visits connected with this study. No payments are available for taking part in this study.

What are the possible benefits and risks of taking part?
Women will be offered pain relief in labour whether they participate in the study or not. We cannot promise the study will help individuals involved, but the answers we get from this study will help improve the care provided to women in labour in the future. Both pethidine and remifentanil are strong drugs related to morphine. Women can experience side effects such as drowsiness, dizziness or sickness with both. All women taking part will be monitored constantly by their midwife for drowsiness and anti-sickness medication given promptly if required. There are no known differences in risks to mother and baby for either type of pain relief. There are no restrictions on having an epidural if needed.

Where is the study run from?
The lead centre for the study is the Birmingham Women’s Hospital (UK).

When is the study starting and how long is it expected to run for?
It is hoped that recruitment will begin in the Autumn of 2013 and run for 20 months.

Who is funding the study?
The National Institute of Health Research (NIHR), UK is funding the research. The NIHR is part of the UK Government, Department of Health.

Who is the main contact?
Leanne Homer
l.e.homer@bham.ac.uk

Trial website

http://www.birmingham.ac.uk/respite

Contact information

Type

Scientific

Primary contact

Dr Leanne Homer

ORCID ID

Contact details

University of Birmingham Clinical Trials Unit
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
l.e.homer@bham.ac.uk

Additional identifiers

EudraCT number

2012-005257-22

ClinicalTrials.gov number

NCT02179294

Protocol/serial number

14923

Study information

Scientific title

Remifentanil intravenous patient controlled analgesia (PCA) versus intramuscular pethidine for pain relief in labour: a randomised controlled trial

Acronym

RESPITE

Study hypothesis

Childbirth can be 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. 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 intrauterine foetal death or foetal abnormality incompatible with survival.

On 23/04/2015 the overall trial end date was changed from 01/06/2015 to 30/11/2015.

Ethics approval

Nottingham 2 MREC, 01/08/2013, ref: 13/EM0239

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Topic: Reproductive Health and Childbirth; Subtopic: Reproductive Health and Childbirth (all Subtopics); Disease: Reproductive Health & Childbirth

Intervention

Women will be randomly allocated to either:
1. Intervention group: Remifentanil via PCA pump (PCA bolus remifentanil 40 µg) administered intravenously
PCA pump programming will be pre-set by anaesthetic staff in accordance to the single protocol indicated above. This dose regime is based on sample guidelines adapted from those used in the introduction of Remifentanil PCA into clinical practice in the applicant's own labour ward and reflect those used in the largest study to date(19;20). In the event of excess sedation being recorded by regular observation of respiratory function (see Section 5.1.2), the regimen will be altered by reduction of the remifentanil bolus dose to 30 µg with a lock-out interval of 2 minutes.
2. Control group: Intramuscular injection of pethidine (100 mg) up to 4 hourly in frequency (up to a maximum of 4 doses). The maximum dose being 400mg in 24 hours.

After the administration of analgesia, a trial participant will receive the following standards of care independent of group allocation:
1. One-to-one midwifery care
2. 30-minute observations including
2.1. Respiratory rate and oxygen saturation by pulse oximetry
2.2. Sedation score
2.3. Visual analogue pain score
Indications for contacting an anaesthesia provider
1. Excessive Sedation Score (not rousable to voice)
2. Respiratory rate <8 breaths/minute
3. Oxygen Saturation <94% whilst breathing room air

There will be no follow-up of patients after discharge from labour ward.

Intervention type

Drug

Phase

Phase IV

Drug names

Remifentanil, Pethidine

Primary outcome measures

The proportion of women who have an epidural placed for pain relief in labour, in each group

Secondary outcome measures

Secondary outcome measures as of 21/12/2015:
1. The effectiveness of pain relief provided by each technique, quantified by Visual Analogue Scale taken every 30 minutes after time zero, until delivery or transfer to theatre.
2. The incidence of maternal side effects, up to the end of 3rd stage, including:
2.1. Excessive sedation score
2.2. Oxygen Saturation <94% whilst breathing room air
2.3. Nausea requiring anti-emetic administration
2.4. Requirement and indication for supplemental oxygen
2.5. Respiratory depression (respiratory rate < 8 breaths/minute)
3. Delivery mode (Spontaneous, Instrumental Vaginal, Caesarean Section)
4. Incidence of foetal distress requiring delivery
5. Neonatal status at delivery:
5.1. APGAR score at 5 minutes
5.2. Incidence of foetal acidosis determined by umbilical cord gas analysis
5.3. Requirement for neonatal resuscitation
5.4. Incidence of and indication for admission to neonatal care
6. Rate of initiation of breastfeeding within the first hour of birth
7. Maternal satisfaction with childbirth experience determined by postpartum questionnaire prior to discharge from the delivery ward
8. Explore and compare women’s birth experiences, perceptions of pain relief and infant feeding behaviours up to six weeks postpartum (RESPITE Post-Natal Sub-Study)

Previous secondary outcome measures:
1. The effectiveness of pain relief provided by each technique, quantified by Visual Analogue Scale taken every 30 minutes after time zero, until delivery or transfer to theatre.
2. The incidence of maternal side effects, up to the end of 3rd stage, including:
2.1. Excessive sedation score
2.2. Oxygen Saturation <94% whilst breathing room air
2.3. Nausea requiring anti-emetic administration
2.4. Requirement for supplemental oxygen
2.5. Respiratory depression (respiratory rate < 8 breaths/minute)
3. Delivery mode (Spontaneous, Instrumental Vaginal, Caesarean Section)
4. Incidence of foetal distress requiring delivery
5. Neonatal status at delivery:
5.1. Apgar score at 5 minutes
5.2. Incidence of foetal acidosis determined by umbilical cord gas analysis
5.3. Requirement for neonatal resuscitation
5.4. Incidence of admission to Special Care Baby Unit
6. Rate of initiation of breastfeeding within the first hour of birth
7. Maternal satisfaction with childbirth experience determined by postpartum questionnaire prior to discharge from the delivery ward
8. Resources used intra- and post-operatively, including PCA consumables, anaesthetist attendance
9. Costs of staff training, service procurement and provision of care will be collected alongside clinical outcomes
10. Explore and compare women’s birth experiences, perceptions of pain relief and infant feeding behaviours up to six weeks postpartum (RESPITE Post-Natal Sub-Study)

Overall trial start date

01/09/2013

Overall trial end date

30/09/2016

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 23/04/2015:
1. Requesting systemic opioid analgesia
2. 16 years of age or older
3. Beyond 37+0 weeks' gestation
4. In established labour (defined as regular painful contractions, irrespective of cervical dilatation) with vaginal birth intended
5. Able to understand all information (written and oral) presented (using an interpreter if necessary) and provide signed consent
6. Not participating in any other clinical trial of a medicinal product
7. Live, singleton pregnancy with cephalic presentation

Previous inclusion criteria:
1. Requesting systemic opioid analgesia
2. 16 years of age or older
3. Beyond 30+0 weeks' gestation
4. In established labour with vaginal birth intended
5. Able to understand all information (written and oral) presented (using an interpreter if necessary) and provide signed consent
6. Not participating in any other clinical trial of a medicinal product
7. Singleton pregnancy with cephalic presentation

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 400; UK Sample Size: 400

Participant exclusion criteria

Exclusion criteria as of 21/12/2015:
1. Contraindication to epidural analgesia
2. Contraindication to intramuscular injection
3. History of a previous adverse reaction to pethidine or remifentanil
4. Patients taking any long-term opioid drug therapy including Methadone
5. Systemic opioid pain relief in 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).

Previous exclusion criteria as of 23/04/2015:
1. Contraindication to epidural analgesia
2. Contraindication to intramuscular injection
3. History of drug sensitivity to pethidine or remifentanil
4. Patients taking any long-term opioid drug therapy including Methadone
5. Systemic opioid pain relief in last 4 hours

Previous exclusion criteria:
1. Contraindication to epidural analgesia
2. Contraindication to intramuscular injection
3. History of drug sensitivity to pethidine or remifentanil
4. Patients taking any long-term opioid drug therapy including Methadone

Recruitment start date

01/05/2014

Recruitment end date

30/09/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Birmingham Women’s Hospital
B15 2TG
United Kingdom

Trial participating centre

University Hospital of North Midlands
ST4 6QG
United Kingdom

Trial participating centre

York Hospital
YO31 8HE
United Kingdom

Trial participating centre

Bradford Royal Infirmary
BD9 6RJ
United Kingdom

Trial participating centre

Frimley Park Hospital
GU16 7UJ
United Kingdom

Trial participating centre

Stoke Mandeville Hospital
HP21 8AL
United Kingdom

Trial participating centre

Northwick Park Hospital
HA1 3UJ
United Kingdom

Trial participating centre

Birmingham Heartlands Hospital
B9 5SS
United Kingdom

Trial participating centre

Good Hope Hospital
B75 7RR
United Kingdom

Trial participating centre

Northwick Park Hospital
Watford Road
Harrow
HA1 3UJ
United Kingdom

Trial participating centre

Norfolk & Norwich University Hospital
NR4 7UY
United Kingdom

Trial participating centre

Medway Maritime Hospital
ME7 5NY
United Kingdom

Trial participating centre

Homerton University Hospital
Homerton Row
London
E9 6SR
United Kingdom

Trial participating centre

City Hospital Birmingham
Dudley Road
Birmingham
B18 7QH
United Kingdom

Trial participating centre

Warwick Hospital
Lakin Road
Warwick
CV34 5BW
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Clinician Scientist Award Scheme, UK; Grant Codes: CS-11-030

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

21/12/2015: At the trialist's request, the record has undergone substantial updates. The recruitment end date and overall trial end date have been extended from 30/11/2015 to 30/09/2016. The secondary outcomes and participant exclusion criteria have been updated. Additionally, New Cross Hospital has been removed as a participating centre, and Northwick Park Hospital, Homerton University Hospital, City Hospital Birmingham and Warwick Hospital have been added as participating centres.