Comparison of Regimens MPIB, CIPCEA, PCEA (COLEUS)

Comparison of Modified Programmed Intermittent Bolus (MPIB), Computer-integrated Patient Controlled Epidural Analgesia (CIPCEA) and Conventional Patient Controlled Epidural Analgesia (PCEA) During Labour

Epidural analgesia is the gold standard of pain relief for labour pain. Despite this, more than 50% of parturients continue to experience pain leading to suffering and increased caregiver workload. Women who have increased pain tend to have lower successful patient bolus demands when patient controlled epidural analgesia (PCEA) is utilised and have dysfunctional labour requiring obstetric intervention such as Caesarean or instrumental delivery. Labour pain often escalates and worsens as labour progresses requiring an individualized, variable, flexible analgesic regimen. Bolus epidural administrations have been shown to improve uniform spread of local anaesthetics with better pain relief, compared to fixed background infusions.

Study Overview

• Status: Active, not recruiting
• Conditions: Breakthrough Pain
• Intervention / Treatment: Device: epidural delivery system; Drug: Ropivacaine; Drug: Fentanyl

Detailed Description

The research team developed two novel epidural delivery regimens: computer-integrated PCEA (CIPCEA) and modified programmed intermittent bolus (MPIB) focused on individualization of analgesic requirements. This phase 3 double-blinded randomized controlled trial will compare the two novel regimens, and each with conventional PCEA with basal infusion (BI), in reducing breakthrough pain (failure of the regimen to provide adequate pain relief, necessitating unscheduled epidural supplementation) incidence as the primary outcome in nulliparous term women requesting labour epidural analgesia. In addition, a discrete choice experiment (DCE) in the format of a survey will be administered to estimate the women's preferences in treatment attributes related to epidural analgesia, including control over epidural dosage, chance of having breakthrough pain, motor block, instrumental delivery and out-of-pocket cost for epidural analgesia. We will also look into the association model for breakthrough pain that would take into account pre-delivery factors to better understand the mechanism of breakthrough pain during labor process.

• Study Type: Interventional
• Enrollment (Actual): 839
• Phase: Phase 3

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 229899
    • KK Women's and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Healthy (ASA physical status 1 and 2) nulliparous parturients at term (≥36 weeks gestation);
2. Singleton foetus
3. Early labour (cervical dilation ≤5cm)
4. Request labour epidural analgesia
5. At least 21 years of age

Exclusion Criteria:

1. parturients with multiple pregnancies
2. non-cephalic foetal presentation
3. obstetric (e.g. pre-eclampsia, premature rupture of amniotic membranes, gestational diabetes on insulin) and uncontrolled medical (e.g. cardiac disease) complications
4. have contraindications to neuraxial blockade or have received parenteral opioids with the last 2 hours.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MPIB modified programmed intermittent bolus; Modified programmed intermittent bolus (MPIB) up-down frequency of 5mls ropivacaine/fentanyl solution in bolus with epidural delivery system	Device: epidural delivery system; epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution; Drug: Ropivacaine; epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution; Other Names: amide local anaesthetic; Drug: Fentanyl; epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution; Other Names: opioid
Experimental: CIPCEA; computer integrated patient controlled epidural analgesia (CIPCEA) up-down variable basal infusion of ropivacaine/fentanyl solution with epidural delivery system	Device: epidural delivery system; epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution; Drug: Ropivacaine; epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution; Other Names: amide local anaesthetic; Drug: Fentanyl; epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution; Other Names: opioid
Active Comparator: patient controlled epidural analgesia with basal infusion; patient controlled epidural analgesia (PCEA) with fixed basal infusion of ropivacaine/fentanyl solution with epidural delivery system	Device: epidural delivery system; epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution; Drug: Ropivacaine; epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution; Other Names: amide local anaesthetic; Drug: Fentanyl; epidural delivery system for maintenance of labour epidural analgesia using 0.1% ropivacaine (amide local anaesthetic) with 2mcg/ml fentanyl (opioid) as maintenance solution; Other Names: opioid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with Breakthrough pain	Unscheduled epidural supplementation by anaesthetist due to pain	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with Caesarean section	Number of subjects with Caesarean section	1 day
Number of subjects with Instrumental delivery	Number of subjects with Instrumental delivery (forceps, vacuum delivery)	1 day
Foetal outcome	APGAR scores	1 day
Willingness to pay	Discrete choice experiments (DCE) in survey format will be given to patients to determine patient's mean willingness to pay for epidural features, including control over epidural dosage, chance of having breakthrough pain, motor block, instrumental delivery and out-of-pocket cost for epidural analgesia)	1 day
Factors associated with epidural decisions	Participants will be exposed to 8 pairs of hypothetical medical scenarios as per the design of DCE. Participants have to choose the ideal scenario (A or B) that provides the highest perceived benefits. Each pair of scenarios represents a comprehensive combination of possible attributes related to epidural analgesia, including control over epidural dosage, chance of having breakthrough pain, motor block, instrumental delivery and out-of-pocket cost for epidural analgesia. The most common factors associated with optimal perceived benefits will be assessed based on these experimental design. A weighted estimate will be calculated for each attribute.	1 day
Pain vulnerability: Pain Catastrophizing Scale	Assessment will be done via Pain Catastrophizing Scale (PCS) questionnaire before delivery. Pain catastrophizing refers to the negative thought processes patients have when they are exposed to pain or painful experiences. The PCS is a 13-item scale, with each item rated on a 5-point scale: 0 (Not at all) to 4 (all the time). It is broken into three subscales being magnification (0-12), rumination (0-16), and helplessness (0-24). A higher value in each subscale indicates a higher tendency to that subscale (worse outcome).	1 day
Edinburgh Postnatal Depression Scale before and after delivery	Assessment will be done via Edinburgh Postnatal Depression Scale (EPDS) before delivery, and again 5 to 9 weeks after delivery to assess patient's status on postnatal depression. The EPDS is a 10 item self-reported questionnaire validated for use as a screening tool for antenatal and postpartum depression in the clinical setting. Participants are asked to respond according to how they have felt in the past seven days, by which the questions correspond to common depressive symptoms. Each item is measured on a 4-point scale, with a total score in the range of 0 to 30. A higher total score indicates a greater degree of depressive symptoms. A score of 13 and above indicates clinically significant depressive symptom.	5-9 weeks
Sub-acute pain after childbirth	Assessment will be done via a pain survey at 5-9 weeks after delivery to ask on patient's pain experience, including the presence of sub-acute pain after childbirth, defined by presence or absence of pain that lasted for 4 weeks or more) (binary variable with categories "yes" or "no").	5-9 weeks

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital
• Investigators: Principal Investigator: Ban L Sng, FANZCA, KK Women's and Children's Hospital

Publications and helpful links

General Publications

• Tan DJA, Lew JP, Jumhasan MB, Pang C, Sultana R, Sng BL. Investigating factors associated with success of breastfeeding in first-time mothers undergoing epidural analgesia: a prospective cohort study. Int Breastfeed J. 2018 Sep 5;13:42. doi: 10.1186/s13006-018-0184-7. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2015
• Primary Completion (Actual): May 6, 2019
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 26, 2014
• First Submitted That Met QC Criteria: October 28, 2014
• First Posted (Estimated): October 30, 2014

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Breakthrough pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Breakthrough Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Anesthetics; Fentanyl; Anesthetics, Local; Ropivacaine
• Other Study ID Numbers: CTGL13feb013