Pregnancy
Conditions
Brief summary
Utilizing a 'minimal local analgesic concentration (MLAC) study' design to first determine the relative potency of Programmed Intermittent Epidural Bolus (PIEB) compared to Continuous Epidural Infusion (CEI) and secondly to determine the mechanism to explain the potential PIEB efficacy advantage.
Detailed description
Pregnant women who present to Labor and Delivery for an anticipated vaginal delivery will be identified as potential participants based on inclusion/exclusion criteria and their desire for labor epidural analgesia. Once identified, interested candidates will be fully informed of the study procedures, have all questions answered, and informed consent obtained. Pregnant participants will receive a labor epidural upon the patient's request and dosed per protocol to adequate analgesic level. Patients will be randomized into 1 of 4 groups. Either group I or II in Study Part A and group III or IV in Study Part B in a double-blinded design. Each study part will run in parallel and independently. Each group will have a varying concentration of bupivicaine infusion; continuous or intermittent bolus administration. In addition each group will have continuous or intermittent bolus administration of sufentanil. These concentrations and forms of administration will be blinded to both the patient and study administrator. Each epidural infusion concentration and continuous or bolus administration will be determined to be a success or failure based on analgesic scores. The investigators' primary outcome will be the minimal local anesthetic concentration of the final participants in each respective group upon study completion. DATA SAFETY MONITORING PLAN will follow standard of clinical care. Any adverse events will be reported to the PI and necessary adjustments to the protocol will be immediately instituted.
Interventions
DRUGBupivacaine
Continuous or bolus administration
DRUGSufentanil
Continuous or bolus administration
Sponsors
Manchester University NHS Foundation Trust
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* ASA I & II, Nulliparous and Multiparous, Spontaneous/Induced/Augmented Labor, Early active labor (cervix \<5 cm (if known)), Pain (VPS) \> 3, 18-45 years of age
Exclusion criteria
* \<37 weeks gestation, H/o Cesarean Section, Multiple Gestation, Pre-eclampsia, Narcotics within 3 hours prior to labor epidural placement, Chronic Pain (as defined by chronic opiate consumption), Women who are participating in another study that will impact protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Local Analgesic Concentration (MLAC) of the Final Participants in Each Respective Group at Study Completion | From initial epidural bolus to delivery (up to approximately 16 hours) | The mean concentration of Bupivacaine in patients who have success or failure outcome were compared between groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Numerical Verbal Pain Scores | Patients were assessed once between initial epidural bolus to delivery (up to 16 hours following initial bolus) | The initial pain score (VAS 0-10 scale with 0 means no pain and 10 means max pain) in patients who have success or failure outcome were compared between groups. |
| Time to First Clinician Rescue Analgesia Request (From Initial Epidural Dose) | From initial epidural bolus to delivery (up to 16 hours following initial bolus) | The time to first clinician rescue analgesia request in patients who have success or failure outcome were compared between groups. |
| Patient Satisfaction With Labor Analgesia | Participants were assessed once from initial epidural bolus to delivery (up to approximately 16 hours) | 0-100% (0 means least satisfaction and 100 means most satisfaction) |
| Labor Outcome (Spontaneous, Assisted, Cesarean) | At the time of delivery | Labor outcome in patients who have success or failure outcome were compared between groups. |
| Number of Participants Requiring Treatment for Pruritus, Nausea and Vomiting, or Hypotension | From initial epidural bolus to delivery (up to 16 hours following initial bolus) | Number of Participants Requiring Treatment for pruritus, nausea and vomiting, and hypotension were reported. |
| Number of Participants With Maternal Nausea/Vomiting | From initial epidural bolus to delivery (up to 16 hours following initial bolus) | yes/no. |
| Protocol Success or Failure | From initial epidural bolus to delivery (up to 16 hours following initial bolus) | Success - No supplemental analgesia request until vaginal exam c/w 8 cm dilation or more -\> 0.01% w/v reduction in subsequent participant's local anesthetic. Failure - Supplemental analgesia request c vaginal exam c/w less than 8 cm dilatation -\>0.01% w/v increase in subsequent LA infusion. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number and Total Dose of Clinician Rescue Boluses | From initial epidural bolus to approximately 6-12 hours following delivery | — |
| Total CEI and PIEB Local Anesthetic and Opioid Use | From initial epidural bolus to delivery (up to 16 hours following initial bolus) | — |
| Requests to Turn Epidural Down or Stop Infusion. | From initial epidural bolus to delivery (up to 16 hours following initial bolus) | yes/no |
| Duration of Epidural Analgesia | From initial epidural bolus to delivery (up to 16 hours following initial bolus) | — |
| Motor Weakness | From initial epidural bolus to delivery (up to 16 hours following initial bolus) | Straight leg lift, yes/no |
| Maternal Pruritis | From initial epidural bolus to delivery (up to 16 hours following initial bolus) | scale from from 0-10 |
Countries
United States
Participant flow
Pre-assignment details
Patients who met the protocol-specified reject criteria were censored (had no subsequent outcome measure data collected and were not considered analyzable for outcome measures) and were considered to have completed the study. Upon reject, catheter management was at discretion of anesthesia care provider.
Participants by arm
| Arm | Count |
|---|---|
| Part A Group 1 CEI bupivacaine and CEI sufentanil
Bupivacaine: Continuous or bolus administration
Sufentanil: Continuous or bolus administration | 8 |
| Part A Group 2 PIEB bupivacaine and PIEB sufentanil
Bupivacaine: Continuous or bolus administration
Sufentanil: Continuous or bolus administration | 6 |
| Part B Group 3 CEI bupivacaine and PIEB sufentanil
Bupivacaine: Continuous or bolus administration
Sufentanil: Continuous or bolus administration | 9 |
| Part B Group 4 PIEB bupivacaine and CEI sufentanil
Bupivacaine: Continuous or bolus administration
Sufentanil: Continuous or bolus administration | 8 |
| Total | 31 |
Baseline characteristics
| Characteristic | Part A Group 1 | Part A Group 2 | Part B Group 3 | Part B Group 4 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 33.5 years STANDARD_DEVIATION 7.2 | 30 years STANDARD_DEVIATION 5.7 | 33.1 years STANDARD_DEVIATION 6.1 | 30.6 years STANDARD_DEVIATION 6.8 | 32.0 years STANDARD_DEVIATION 6.4 |
| Race/Ethnicity, Customized American Indian/Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 4 Participants | 2 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 1 Participants | 5 Participants | 3 Participants | 14 Participants |
| Region of Enrollment United States | 8 Participants | 6 Participants | 9 Participants | 8 Participants | 31 Participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 9 Participants | 8 Participants | 31 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 6 | 0 / 9 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 9 | 0 / 8 |
Outcome results
Primary
Minimum Local Analgesic Concentration (MLAC) of the Final Participants in Each Respective Group at Study Completion
The mean concentration of Bupivacaine in patients who have success or failure outcome were compared between groups.
Time frame: From initial epidural bolus to delivery (up to approximately 16 hours)
Population: Analyzable data set (did not meet the protocol-specified reject criteria).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A Group 1 | Minimum Local Analgesic Concentration (MLAC) of the Final Participants in Each Respective Group at Study Completion | 0.06 % mg/ml | Standard Deviation 0.008 |
| Part A Group 2 | Minimum Local Analgesic Concentration (MLAC) of the Final Participants in Each Respective Group at Study Completion | 0.06 % mg/ml | Standard Deviation 0.007 |
| Part B Group 3 | Minimum Local Analgesic Concentration (MLAC) of the Final Participants in Each Respective Group at Study Completion | 0.075 % mg/ml | Standard Deviation 0.01 |
| Part B Group 4 | Minimum Local Analgesic Concentration (MLAC) of the Final Participants in Each Respective Group at Study Completion | 0.072 % mg/ml | Standard Deviation 0.008 |
Secondary
Labor Outcome (Spontaneous, Assisted, Cesarean)
Labor outcome in patients who have success or failure outcome were compared between groups.
Time frame: At the time of delivery
Population: Analyzable data set (did not meet the protocol-specified reject criteria).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Group 1 | Labor Outcome (Spontaneous, Assisted, Cesarean) | C-section | 1 Participants |
| Part A Group 1 | Labor Outcome (Spontaneous, Assisted, Cesarean) | Spontaneous | 3 Participants |
| Part A Group 2 | Labor Outcome (Spontaneous, Assisted, Cesarean) | Spontaneous | 3 Participants |
| Part A Group 2 | Labor Outcome (Spontaneous, Assisted, Cesarean) | C-section | 2 Participants |
| Part B Group 3 | Labor Outcome (Spontaneous, Assisted, Cesarean) | Spontaneous | 4 Participants |
| Part B Group 3 | Labor Outcome (Spontaneous, Assisted, Cesarean) | C-section | 2 Participants |
| Part B Group 4 | Labor Outcome (Spontaneous, Assisted, Cesarean) | C-section | 0 Participants |
| Part B Group 4 | Labor Outcome (Spontaneous, Assisted, Cesarean) | Spontaneous | 6 Participants |
Secondary
Number of Participants Requiring Treatment for Pruritus, Nausea and Vomiting, or Hypotension
Number of Participants Requiring Treatment for pruritus, nausea and vomiting, and hypotension were reported.
Time frame: From initial epidural bolus to delivery (up to 16 hours following initial bolus)
Population: Analyzable data set (did not meet the protocol-specified reject criteria).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Group 1 | Number of Participants Requiring Treatment for Pruritus, Nausea and Vomiting, or Hypotension | 0 Participants |
| Part A Group 2 | Number of Participants Requiring Treatment for Pruritus, Nausea and Vomiting, or Hypotension | 0 Participants |
| Part B Group 3 | Number of Participants Requiring Treatment for Pruritus, Nausea and Vomiting, or Hypotension | 2 Participants |
| Part B Group 4 | Number of Participants Requiring Treatment for Pruritus, Nausea and Vomiting, or Hypotension | 3 Participants |
Secondary
Number of Participants With Maternal Nausea/Vomiting
yes/no.
Time frame: From initial epidural bolus to delivery (up to 16 hours following initial bolus)
Population: Analyzable data set (did not meet the protocol-specified reject criteria).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Group 1 | Number of Participants With Maternal Nausea/Vomiting | 0 Participants |
| Part A Group 2 | Number of Participants With Maternal Nausea/Vomiting | 0 Participants |
| Part B Group 3 | Number of Participants With Maternal Nausea/Vomiting | 0 Participants |
| Part B Group 4 | Number of Participants With Maternal Nausea/Vomiting | 2 Participants |
Secondary
Numerical Verbal Pain Scores
The initial pain score (VAS 0-10 scale with 0 means no pain and 10 means max pain) in patients who have success or failure outcome were compared between groups.
Time frame: Patients were assessed once between initial epidural bolus to delivery (up to 16 hours following initial bolus)
Population: Analyzable data set (did not meet the protocol-specified reject criteria).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A Group 1 | Numerical Verbal Pain Scores | 6.3 score on a scale | Standard Deviation 1 |
| Part A Group 2 | Numerical Verbal Pain Scores | 8.4 score on a scale | Standard Deviation 0.9 |
| Part B Group 3 | Numerical Verbal Pain Scores | 7.7 score on a scale | Standard Deviation 2.1 |
| Part B Group 4 | Numerical Verbal Pain Scores | 8.2 score on a scale | Standard Deviation 1 |
Secondary
Patient Satisfaction With Labor Analgesia
0-100% (0 means least satisfaction and 100 means most satisfaction)
Time frame: Participants were assessed once from initial epidural bolus to delivery (up to approximately 16 hours)
Population: Analyzable data set (did not meet the protocol-specified reject criteria).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A Group 1 | Patient Satisfaction With Labor Analgesia | 97.3 score on a scale | Standard Deviation 4.9 |
| Part A Group 2 | Patient Satisfaction With Labor Analgesia | 97.6 score on a scale | Standard Deviation 4.3 |
| Part B Group 3 | Patient Satisfaction With Labor Analgesia | 99.2 score on a scale | Standard Deviation 2 |
| Part B Group 4 | Patient Satisfaction With Labor Analgesia | 96.7 score on a scale | Standard Deviation 5.2 |
Secondary
Protocol Success or Failure
Success - No supplemental analgesia request until vaginal exam c/w 8 cm dilation or more -\> 0.01% w/v reduction in subsequent participant's local anesthetic. Failure - Supplemental analgesia request c vaginal exam c/w less than 8 cm dilatation -\>0.01% w/v increase in subsequent LA infusion.
Time frame: From initial epidural bolus to delivery (up to 16 hours following initial bolus)
Population: Analyzable data set (did not meet the protocol-specified reject criteria).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Group 1 | Protocol Success or Failure | Success | 1 Participants |
| Part A Group 1 | Protocol Success or Failure | Failure | 3 Participants |
| Part A Group 2 | Protocol Success or Failure | Failure | 2 Participants |
| Part A Group 2 | Protocol Success or Failure | Success | 3 Participants |
| Part B Group 3 | Protocol Success or Failure | Success | 2 Participants |
| Part B Group 3 | Protocol Success or Failure | Failure | 4 Participants |
| Part B Group 4 | Protocol Success or Failure | Success | 2 Participants |
| Part B Group 4 | Protocol Success or Failure | Failure | 4 Participants |
Secondary
Time to First Clinician Rescue Analgesia Request (From Initial Epidural Dose)
The time to first clinician rescue analgesia request in patients who have success or failure outcome were compared between groups.
Time frame: From initial epidural bolus to delivery (up to 16 hours following initial bolus)
Population: Analyzable data set (did not meet the protocol-specified reject criteria).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A Group 1 | Time to First Clinician Rescue Analgesia Request (From Initial Epidural Dose) | 4.3 hours | Standard Deviation 1.7 |
| Part A Group 2 | Time to First Clinician Rescue Analgesia Request (From Initial Epidural Dose) | 5.3 hours | Standard Deviation 1.2 |
| Part B Group 3 | Time to First Clinician Rescue Analgesia Request (From Initial Epidural Dose) | 7.5 hours | Standard Deviation 5.2 |
| Part B Group 4 | Time to First Clinician Rescue Analgesia Request (From Initial Epidural Dose) | 4.8 hours | Standard Deviation 3 |
Other Pre-specified
Duration of Epidural Analgesia
Time frame: From initial epidural bolus to delivery (up to 16 hours following initial bolus)
Other Pre-specified
Maternal Pruritis
scale from from 0-10
Time frame: From initial epidural bolus to delivery (up to 16 hours following initial bolus)
Other Pre-specified
Motor Weakness
Straight leg lift, yes/no
Time frame: From initial epidural bolus to delivery (up to 16 hours following initial bolus)
Other Pre-specified
Number and Total Dose of Clinician Rescue Boluses
Time frame: From initial epidural bolus to approximately 6-12 hours following delivery
Other Pre-specified
Requests to Turn Epidural Down or Stop Infusion.
yes/no
Time frame: From initial epidural bolus to delivery (up to 16 hours following initial bolus)
Other Pre-specified
Total CEI and PIEB Local Anesthetic and Opioid Use
Time frame: From initial epidural bolus to delivery (up to 16 hours following initial bolus)