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CompletedNCT03307174Updated May 12, 2020Results posted

Programmed Intermittent Bolus Dosing Versus Continuous Epidural Infusion for Epidural Analgesia in Abdominal Surgery.

A Phase 4 interventional study of Bupivacaine and Fentanyl in Pain, Acute, sponsored by University of California, San Francisco. Completed at 1 site in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-05-12.

Sponsored by University of California, San Francisco · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Epidurals are an effective means for providing neuraxial anesthesia and analgesia. Prior studies in labor epidurals have demonstrated that a programmed intermittent bolus application of local anesthesia can improve pain control by reducing the amount of local anesthetic required as well as improve patient satisfaction when compared to continuous epidural infusions. The effects of programmed intermittent bolus of epidural local anesthetics compared to continuous epidural infusions in a surgical setting have yet to be elucidated. Our goal is to evaluate the use of programmed intermittent bolus compared to continuous epidural infusion in a surgical patient population. We plan to enroll patients already undergoing abdominal surgeries including colorectal, gynecologic, surgical oncology, urological where epidural anesthesia can be employed. The primary endpoints of the study will be the total local anesthetic consumption and total opioid consumption as surrogate markers for the quality of epidural anesthesia. Secondary endpoints are pain scores and functional measurements, patient satisfaction, and incidence of hypotension.

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02

Conditions studied

  • Pain, Acute

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03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • American Society of Anesthesia physical classification I - III, scheduled for surgery with anticipated an epidural anesthesia (including but not limited to colorectal, surgical oncology, urology, gynecology) as part of their perioperative treatment

Exclusion criteria

Exclusion Criteria:

  • Age younger than 18 years of age, non-English speaking, contraindication for neuraxial anesthesia (such as, but not limited to coagulopathy, infection at site, allergy to local anesthetic), preexisting neurologic deficits, inability to consent due to cognitive dysfunction, patients with pain numeric rating score > 5 each day for greater than 3 months, daily opioid consumption > 100 oral morphine equivalents for 14 consecutive days prior to surgery, patient refusal.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
120 participants (actual)

Study arms

  • Active comparator
    Continuous epidural infusion

    At our institution, the most commonly utilized form of administration of medication through an epidural (our active comparator/control) is as follows: Combination of 0.0625% bupivacaine with 2mcg/ml of fentanyl infused at a constant rate of 8ml/hr. The patient has the ability to self administer patient controlled epidural analgesia of 2ml of the epidural medication with a lock out period of 15 min. The total maximum volume of epidural medication each hour is 16ml. These settings are managed and controlled by a epidural medication pump. Additional oral and intravenous analgesia medications are available as scheduled and pro re nata.

    Drug: Bupivacaine · Drug: Fentanyl

  • Experimental
    Programmed intermittent epidural bolus

    For the programmed intermittent epidural bolus group: Combination of 0.0625% bupivacaine with 2mcg/ml of fentanyl will be administered as a bolus of 4ml every 30 minutes. The patient has the ability to self administer patient controlled epidural analgesia of 2ml of the epidural medication with a lock out period of 10 min. The total maximum volume of epidural medication each hour is 16ml. These settings are managed and controlled by a epidural medication pump. Additional oral and intravenous analgesia medications are available as scheduled and pro re nata.

    Drug: Bupivacaine · Drug: Fentanyl

Interventions

  • DrugBupivacaine

    Also known as: 0.0625% bupivacaine

  • DrugFentanyl

    Also known as: 2mcg/ml fentanyl

05

What researchers measure

Primary outcomes

  1. Total Local Anesthetic Utilized in First 24 Hours

    Total local anesthetic consumed while epidural in place, recorded on infusion pump

    Time frame: In first 24 hours

Secondary outcomes

  1. Total Opioid Consumed

    Total opioid consumed (intravenous or po) while epidural in place

    Time frame: While epidural in place (up to 72 hours post operatively)

  2. Patient Satisfaction Score

    Ranked patient satisfaction scores while epidural in place. Measured by modified pain inventory. Minimum is 0, maximum of 10. 10 indicates highest patient satisfaction.

    Time frame: While epidural in place (up to 72 hours postoperatively)

  3. Average Pain Severity

    Measured by modified pain inventory on a daily basis while epidural in place. Minimum is 0, maximum is 10. 10 indicates highest pain severity.

    Time frame: While epidural in place (up to 72 hours postoperatively)

  4. Incidence of Hypotension

    Most common side effect post-operatively with epidural anesthesia. Documented by recorded vitals signs, fluid resuscitation, and temporary cessation of epidural medication.

    Time frame: While epidural in place (24 hours postoperatively)

  5. Worst Reported 24 Hour Pain

    Minimum is 0, maximum is 10. 10 indicates highest pain severity.

    Time frame: While epidural in place (up to 72 hours postoperatively)

  6. Average Pain Interference

    Minimum is 0, maximum is 10. 10 indicates highest pain interference.

    Time frame: While epidural in place (up to 72 hours postoperatively)

06

Results

Posted May 12, 2020

Participant flow

Patients were enrolled between December 2016 to December 2018

Participant flow — Overall Study
MilestoneContinuous Epidural InfusionProgrammed Intermittent Epidural Bolus
Started6060
Completed4653
Not completed147
Withdrew: Unplanned icu administrion53
Withdrew: Aborted surgery12
Withdrew: Hypotension60
Withdrew: Nonfunctional epidural11
Withdrew: Planned epidural removal10
Withdrew: Intrathecal catheter placement01

Outcome measures

PrimaryTotal Local Anesthetic Utilized in First 24 Hours

Total local anesthetic consumed while epidural in place, recorded on infusion pump

Time frame:
In first 24 hours
Reported as:
Median · mg
Total Local Anesthetic Utilized in First 24 Hours
mgContinuous Epidural InfusionProgrammed Intermittent Epidural Bolus
Total Local Anesthetic Utilized in First 24 Hours126 (120 to 134)123 (115 to 136)
Statistical analysis
  • Continuous Epidural Infusion vs Programmed Intermittent Epidural Bolus · Wilcoxon (Mann-Whitney) · p = 0.74
SecondaryTotal Opioid Consumed

Total opioid consumed (intravenous or po) while epidural in place

Time frame:
While epidural in place (up to 72 hours post operatively)
Reported as:
Median · MME
Total Opioid Consumed
MMEContinuous Epidural InfusionProgrammed Intermittent Epidural Bolus
24 hours postoperatively12 (0 to 28)16 (0 to 27)
24 - 48 hours postoperatively0 (0 to 25)0 (0 to 30)
48 - 72 hrs postoperatively0 (0 to 21)1 (0 to 18)
SecondaryPatient Satisfaction Score

Ranked patient satisfaction scores while epidural in place. Measured by modified pain inventory. Minimum is 0, maximum of 10. 10 indicates highest patient satisfaction.

Time frame:
While epidural in place (up to 72 hours postoperatively)
Reported as:
Median · score on a scale
Patient Satisfaction Score
score on a scaleContinuous Epidural InfusionProgrammed Intermittent Epidural Bolus
24 hours postoperatively9 (8 to 10)8 (6.5 to 10)
24 - 48 hours postoperatively9 (7 to 10)9 (7.3 to 10)
48 - 72 hours postoperatively9 (7 to 10)9 (8 to 10)
SecondaryAverage Pain Severity

Measured by modified pain inventory on a daily basis while epidural in place. Minimum is 0, maximum is 10. 10 indicates highest pain severity.

Time frame:
While epidural in place (up to 72 hours postoperatively)
Reported as:
Median · units on a scale
Average Pain Severity
units on a scaleContinuous Epidural InfusionProgrammed Intermittent Epidural Bolus
24 hours postoperatively3 (1 to 4)5 (2 to 5)
24 - 48 hours postoperatively3 (1 to 4)2 (1 to 5)
48 - 72 hours postoperatively3 (1 to 4)3 (1 to 4)
SecondaryIncidence of Hypotension

Most common side effect post-operatively with epidural anesthesia. Documented by recorded vitals signs, fluid resuscitation, and temporary cessation of epidural medication.

Time frame:
While epidural in place (24 hours postoperatively)
Reported as:
Count of participants · Participants
Incidence of Hypotension
ParticipantsContinuous Epidural InfusionProgrammed Intermittent Epidural Bolus
Incidence of Hypotension918
SecondaryWorst Reported 24 Hour Pain

Minimum is 0, maximum is 10. 10 indicates highest pain severity.

Time frame:
While epidural in place (up to 72 hours postoperatively)
Reported as:
Median · score on a scale
Worst Reported 24 Hour Pain
score on a scaleContinuous Epidural InfusionProgrammed Intermittent Epidural Bolus
24 hours postoperatively5 (2 to 7)8 (4 to 9)
24 - 48 hours postoperatively6 (3 to 8)6 (3 to 8)
48 - 72 hours postoperativley7 (5 to 8)6 (3 to 8)
SecondaryAverage Pain Interference

Minimum is 0, maximum is 10. 10 indicates highest pain interference.

Time frame:
While epidural in place (up to 72 hours postoperatively)
Reported as:
Median · score on a scale
Average Pain Interference
score on a scaleContinuous Epidural InfusionProgrammed Intermittent Epidural Bolus
24 hours postoperatively2 (0 to 4)3 (1 to 5)
24 - 48 hours postoperatively1 (0 to 4)1 (0 to 4)
48 - 72 hours postoperatively2 (0 to 4)1 (0 to 3)

Adverse events

Collected over Data collected from day of surgery until removal of epidural, on average epidurals were removed between day 1 and 3. Rare clinical scenarios, epidurals can remain as long as 7 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Continuous Epidural Infusion0/44 (0%)0/44 (0%)9/44 (20.5%)
Programmed Intermittent Epidural Bolus0/52 (0%)0/52 (0%)18/52 (34.6%)
Most frequent other events
Most frequent other events
EventContinuous Epidural InfusionProgrammed Intermittent Epidural Bolus
HypotensionCardiac disorders9/4418/52

Baseline characteristics

Age, Continuous
Age, Continuous(years)Continuous Epidural InfusionProgrammed Intermittent Epidural BolusTotal
Mean58 ± 1455 ± 1657 ± 15
Sex: Female, Male
Sex: Female, Male(Participants)Continuous Epidural InfusionProgrammed Intermittent Epidural BolusTotal
Female424385
Male181735
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Continuous Epidural InfusionProgrammed Intermittent Epidural BolusTotal
White424082
Latinx7916
Black/African American011
Asian/Pacific Islander111021
Home Medication Use
Home Medication Use(Participants)Continuous Epidural InfusionProgrammed Intermittent Epidural BolusTotal
Acetaminophen131629
NSAIDS141125
Gabapentinoids246
TCA/SNRI000
Daily opioid consumption
Daily opioid consumption(MME)Continuous Epidural InfusionProgrammed Intermittent Epidural BolusTotal
Median0 (0 to 0)0 (0 to 0)0 (0 to 0)
Pain Severity
Pain Severity(units on a scale)Continuous Epidural InfusionProgrammed Intermittent Epidural BolusTotal
Current Pain0 (0 to 0)0 (0 to 0)0 (0 to 0)
Worst Pain2 (0 to 6)4 (0 to 7)3 (0 to 7)
Least Pain0 (0 to 1)0 (0 to 2)0 (0 to 1)
Average Pain1 (0 to 4)2 (0 to 4)1 (0 to 4)
Average Pain Interference
Average Pain Interference(units on a scale)Continuous Epidural InfusionProgrammed Intermittent Epidural BolusTotal
Median1 (0 to 3)2 (0 to 6)1 (0 to 4)
World Health Organization Disability Assessment Schedule 2.0
World Health Organization Disability Assessment Schedule 2.0(units on a scale)Continuous Epidural InfusionProgrammed Intermittent Epidural BolusTotal
Mean12 (4 to 30)19 (12 to 32)17 (8 to 31)

5 further baseline measures are reported on the registry.

07

Study locations

1 site
  • University of California San Francisco
    San Francisco, California 94158, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jul 30, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03307174
Lead sponsor
University of California, San Francisco
Responsible party
Sponsor
First posted
Oct 11, 2017
Start date
Apr 14, 2016
Primary completion
Feb 28, 2019
Completion
Feb 28, 2019
Results posted
May 12, 2020
Last update
May 12, 2020

Study contacts

Matthias Behrends, MD
principal investigator · University of California, San Francisco

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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