PainPhase 4CADD2NCT03553576
Drug Concentration and Volume on Adequate Labor Analgesia With PIEB
A Phase 4 study testing Low volume bolus and High volume bolus in people with Pain and Anesthesia, run by Northwestern University at 1 site in United States.
Trial summary
Neuraxial labor analgesia is performed by the administration of a local anesthetic/opioid mixture in the epidural space. The delivery method is a combination of continuous infusion, provider-administered boluses and patient-administered boluses (patient controlled epidural analgesia [PCEA]) via epidural catheter. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Pain, Anesthesia, Labor Pain
- What is being tested?
- Low volume bolus and High volume bolus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 146 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jan 2020to 1 Jun 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years and above
- Nulliparous parturients
- Present to the labor and delivery unit for an induction of labor or who are in spontaneous labor
- Request neuraxial labor analgesia at ≤5 cm cervical dilation
Who cannot join
- Patients who are not eligible to receive a combined spinal epidural (CSE) technique with 25 mcg of intrathecal fentanyl
- Non-English speaking
- Failed initiation of CSE analgesia (VAS pain score >10 15 minutes after intrathecal dose)
- Need to have the epidural catheter replaced during labor
- Who deliver within 90 minutes of initiation of labor analgesia
- Require re-dose within 90 minutes of initiation of labor analgesia.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Relationship Between Local Anesthetic Concentration and Volume on Adequate Labor Analgesia With Programmed Intermittent Epidural Bolus
Neuraxial labor analgesia is performed by the administration of a local anesthetic/opioid mixture in the epidural space. The delivery method is a combination of continuous infusion, provider-administered boluses and patient-administered boluses (patient controlled epidural analgesia [PCEA]) via epidural catheter. The anesthetic solution administered through the lumbar epidural catheter must spread cephalad in the epidural space to reach the T10 nerve roots and spinal cord, and must spread caudad to reach the caudal nerve roots in the epidural space.
Epidural infusion pumps capable of delivering PIEB of local anesthetic with PCEA have become commercially available and many studies have attempted to assess the optimal parameter settings (including volume of programmed bolus, bolus interval, rate of bolus administration) to provide superior labor analgesia.
Read more
Traditionally higher concentration local anesthetic solutions have been associated with increased motor blockade leading to a higher incidence of instrumental vaginal delivery. Several local anesthetic solutions with varying drug concentrations are available for labor analgesia and are used clinically in the United States. We plan to perform a randomized, controlled, double-blind study to test the hypothesis that patients whose labor analgesia is maintained using PIEB with low-volume bolus (6.25 mL) of a higher local anesthetic concentration solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) will require less supplemental analgesia (manual provider re-doses) than patients whose PIEB is delivered with a high-volume bolus (10 mL) of lower density local anesthetic solution (0.0625% bupivacaine with fentanyl 2.0 mcg/mL).
The aim of this study is to evaluate the association between bolus volume and concentration of local anesthetic during maintenance of labor analgesia with programmed intermittent epidural bolus (PIEB) analgesia.
The hypothesis of this study is: patients whose labor analgesia is maintained using PIEB with low-volume bolus (6.25 mL) of higher local anesthetic concentration solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) will have a longer duration of adequate analgesia (time to first manual re-dose request) than patients whose PIEB is delivered with a high-volume bolus (10 mL) of lower concentration local anesthetic solution (0.0625% bupivacaine with fentanyl 2.0 mcg/mL).
- Conditions
- Pain, Anesthesia, Labor Pain
- Being tested
- Low volume bolus, High volume bolus
- Keywords
- Labor pain, Epidural, Obstetric, Labor Analgesia
- Medical subject headings
- Pain, Labor Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low volume bolusDrug
Administration of a low-volume bolus (6.25 mL) of greater density solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) at 250 mL per hour given by CADD pump.
High volume bolusDrug
Administration of a high-volume bolus (10 mL) of lower density local anesthetic (0.0625% bupivacaine with fentanyl 2.0 mcg/mL) at 250 mL per hour given by CADD pump.
| Study group | Role | What they receive |
|---|---|---|
| Low volume bolus | Experimental | 6.25 mL administration at 250 ml per hour of a greater density solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) Receives: Drug: Low volume bolus |
| High volume bolus | Experimental | 10 mL administration of a lower density local anesthetic (0.0625% bupivacaine with fentanyl 2.0 mcg/mL). Receives: Drug: High volume bolus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anesthesia Provider Administered Bolus
Anesthesia provider (MD) administered boluses of additional anesthetic administered prior to the delivery of the baby.
Measured: 72 hours
Secondary outcomes (14)
VAS at 10 Centimeters Dilation of Cervix
VAS (visual analogue scale) at 10 centimeters dilation of cervix on a scale of 0 (no pain,good) to 100 (worst pain imaginable,bad)
Measured: 24 hours
VAS Score After Delivery
VAS score (Visual Analogue Scale) on a score of 0 (no pain,good) to 100 (worst pain imaginable,bad) immediately after delivery of baby
Measured: 24 hours
Intrascapular Pain
Number of participants who experienced intrascapular pain (pain in your shoulder blade) during the study period.
Measured: 72 hours
Provider Administered Bolus
Number of participants requiring anesthesia provider administration of additional bolus doses of pain medication.
Measured: 72 hours
Number of Participants Who Required Additional Provider Redoses
Additional number of participants who required additional anesthesia care provider redoses of pain medication.
Measured: 72 hours
Time to First Anesthesiology Provider Bolus
Time elapsed in minutes from epidural set up to time to request supplemental analgesia provided by the anesthesiology care provider.
Measured: 72 hours
VAS Score Prior to First Provider Bolus Dose
Patient reported visual analogue scale score (0 no pain,good-100 worst pain imaginable, bad) prior to the first anesthesiology care provider bolus dose of anesthetic (pain medication).
Measured: 72 hours
VAS Score 30 Minutes After Anesthetic Care Provider Dose
Patient reported visual analogue scale score (0 no pain, good -100 worst pain imaginable, bad) 30 minutes after the first anesthesiology care provider bolus dose of anesthetic was administered to the participant for pain relief.
Measured: 72 hours
Bupivacaine Consumption Per Hour
Average consumption of bupivacaine in milligrams per hour.
Measured: 72 hours
Maximum Oxytocin Dose
Maximum oxytocin dose administered intravenously in international units.
Measured: 72 hours
Time of Intrathecal Administration to Delivery
Elapsed time in minutes from the intrathecal administration of anesthetic by anesthesiology provider to time of delivery of baby.
Measured: 72 hours
Number of Participants Categorized by Mode of Delivery
Mode of delivery identified as: normal vaginal delivery, instrumental vaginal delivery, cesarean delivery or emergency cesarean delivery
Measured: 72 hours
PCA Boluses
Number of Patient-Controlled Epidural Analgesia (PCEA) boluses of pain medication requested and number of PCEA medication boluses administered.
Measured: 72 hours
PCA Boluses Ratio
The ratio of the number of Patient-Controlled Epidural Analgesia (PCEA) pain medication boluses requested and number of PCEA pain medication boluses administered by the PCEA pump.
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2018
- Study start21 Jan 2020
- Primary completion31 May 2023
- Study completion1 Jun 2023
Why it stopped: Lack of continued funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two group randomized controlled trial
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Feyce M. Peralta, MD, MS, Northwestern University
- Investigators
- Feyce Peralta, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03553576
- Sponsor's protocol ID
- STU00206113
- Acronym
- CADD2
- Status last verified
- May 2025
- First submitted
- 30 May 2018
- Last updated
- 21 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Wong CA, Ratliff JT, Sullivan JT, Scavone BM, Toledo P, McCarthy RJ. A randomized comparison of programmed intermittent epidural bolus with continuous epidural infusion for labor analgesia. Anesth Analg. 2006 Mar;102(3):904-9. doi: 10.1213/01.ane.0000197778.57615.1a.
PubMed 16492849Lim Y, Sia AT, Ocampo C. Automated regular boluses for epidural analgesia: a comparison with continuous infusion. Int J Obstet Anesth. 2005 Oct;14(4):305-9. doi: 10.1016/j.ijoa.2005.05.004.
PubMed 16154735Chua SM, Sia AT. Automated intermittent epidural boluses improve analgesia induced by intrathecal fentanyl during labour. Can J Anaesth. 2004 Jun-Jul;51(6):581-5. doi: 10.1007/BF03018402.
PubMed 15197122Kaynar AM, Shankar KB. Epidural infusion: continuous or bolus? Anesth Analg. 1999 Aug;89(2):534. doi: 10.1097/00000539-199908000-00063. No abstract available.
PubMed 10439786Hogan Q. Distribution of solution in the epidural space: examination by cryomicrotome section. Reg Anesth Pain Med. 2002 Mar-Apr;27(2):150-6. doi: 10.1053/rapm.2002.29748.
PubMed 11915061Comparative Obstetric Mobile Epidural Trial (COMET) Study Group UK. Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial. Lancet. 2001 Jul 7;358(9275):19-23. doi: 10.1016/S0140-6736(00)05251-X.
PubMed 11454372
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relationship Between Local Anesthetic Concentration and Volume on Adequate Labor Analgesia With Programmed Intermittent Epidural Bolus
- ClinicalTrials.gov ID
- NCT03553576
- Acronym / sponsor ID
- CADD2 / STU00206113
- Conditions
- Pain, Anesthesia, Labor Pain
- Keywords
- Labor pain, Epidural, Obstetric, Labor Analgesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of continued funding
- Enrolment
- 146 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- 21 Jan 2020 (actual)
- Primary completion
- 31 May 2023 (actual)
- Study completion
- 1 Jun 2023 (actual)
- First posted
- 12 Jun 2018 (actual)
- Results
- Posted 21 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neuraxial labor analgesia is performed by the administration of a local anesthetic/opioid mixture in the epidural space. The delivery method is a combination of continuous infusion, provider-administered boluses and patient-administered boluses (patient controlled epidural analgesia [PCEA]) via epidural catheter. The anesthetic solution administered through the lumbar epidural catheter must spread cephalad in the epidural space to reach the T10 nerve roots and spinal cord, and must spread caudad to reach the caudal nerve roots in the epidural space.
Epidural infusion pumps capable of delivering PIEB of local anesthetic with PCEA have become commercially available and many studies have attempted to assess the optimal parameter settings (including volume of programmed bolus, bolus interval, rate of bolus administration) to provide superior labor analgesia.
Traditionally higher concentration local anesthetic solutions have been associated with increased motor blockade leading to a higher incidence of instrumental vaginal delivery. Several local anesthetic solutions with varying drug concentrations are available for labor analgesia and are used clinically in the United States. We plan to perform a randomized, controlled, double-blind study to test the hypothesis that patients whose labor analgesia is maintained using PIEB with low-volume bolus (6.25 mL) of a higher local anesthetic concentration solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) will require less supplemental analgesia (manual provider re-doses) than patients whose PIEB is delivered with a high-volume bolus (10 mL) of lower density local anesthetic solution (0.0625% bupivacaine with fentanyl 2.0 mcg/mL).
The aim of this study is to evaluate the association between bolus volume and concentration of local anesthetic during maintenance of labor analgesia with programmed intermittent epidural bolus (PIEB) analgesia.
The hypothesis of this study is: patients whose labor analgesia is maintained using PIEB with low-volume bolus (6.25 mL) of higher local anesthetic concentration solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) will have a longer duration of adequate analgesia (time to first manual re-dose request) than patients whose PIEB is delivered with a high-volume bolus (10 mL) of lower concentration local anesthetic solution (0.0625% bupivacaine with fentanyl 2.0 mcg/mL).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Two group randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Low volume bolus | Experimental | Drug: Low volume bolus6.25 mL administration at 250 ml per hour of a greater density solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) |
| High volume bolus | Experimental | Drug: High volume bolus10 mL administration of a lower density local anesthetic (0.0625% bupivacaine with fentanyl 2.0 mcg/mL). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18 years and above
- Nulliparous parturients
- Present to the labor and delivery unit for an induction of labor or who are in spontaneous labor
- Request neuraxial labor analgesia at ≤5 cm cervical dilation
Key exclusion criteria (6 listed)
- Patients who are not eligible to receive a combined spinal epidural (CSE) technique with 25 mcg of intrathecal fentanyl
- Non-English speaking
- Failed initiation of CSE analgesia (VAS pain score >10 15 minutes after intrathecal dose)
- Need to have the epidural catheter replaced during labor
- Who deliver within 90 minutes of initiation of labor analgesia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low volume bolusAdministration of a low-volume bolus (6.25 mL) of greater density solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) at 250 mL per hour given by CADD pump. | Drug | Low volume bolus |
| High volume bolusAdministration of a high-volume bolus (10 mL) of lower density local anesthetic (0.0625% bupivacaine with fentanyl 2.0 mcg/mL) at 250 mL per hour given by CADD pump. | Drug | High volume bolus |
Primary outcome
Anesthesia Provider Administered Bolus
Time frame: 72 hours
Anesthesia provider (MD) administered boluses of additional anesthetic administered prior to the delivery of the baby.
14 secondary outcomes
VAS at 10 Centimeters Dilation of Cervix
Time frame: 24 hours
VAS Score After Delivery
Time frame: 24 hours
Intrascapular Pain
Time frame: 72 hours
Provider Administered Bolus
Time frame: 72 hours
Number of Participants Who Required Additional Provider Redoses
Time frame: 72 hours
Time to First Anesthesiology Provider Bolus
Time frame: 72 hours
VAS Score Prior to First Provider Bolus Dose
Time frame: 72 hours
VAS Score 30 Minutes After Anesthetic Care Provider Dose
Time frame: 72 hours
Bupivacaine Consumption Per Hour
Time frame: 72 hours
Maximum Oxytocin Dose
Time frame: 72 hours
Time of Intrathecal Administration to Delivery
Time frame: 72 hours
Number of Participants Categorized by Mode of Delivery
Time frame: 72 hours
PCA Boluses
Time frame: 72 hours
PCA Boluses Ratio
Time frame: 72 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16492849Wong CA, Ratliff JT, Sullivan JT, Scavone BM, Toledo P, McCarthy RJ. A randomized comparison of programmed intermittent epidural bolus with continuous epidural infusion for labor analgesia. Anesth Analg. 2006 Mar;102(3):904-9. doi: 10.1213/01.ane.0000197778.57615.1a.
- Background: PubMed 16154735Lim Y, Sia AT, Ocampo C. Automated regular boluses for epidural analgesia: a comparison with continuous infusion. Int J Obstet Anesth. 2005 Oct;14(4):305-9. doi: 10.1016/j.ijoa.2005.05.004.
- Background: PubMed 15197122Chua SM, Sia AT. Automated intermittent epidural boluses improve analgesia induced by intrathecal fentanyl during labour. Can J Anaesth. 2004 Jun-Jul;51(6):581-5. doi: 10.1007/BF03018402.
- Background: PubMed 10439786Kaynar AM, Shankar KB. Epidural infusion: continuous or bolus? Anesth Analg. 1999 Aug;89(2):534. doi: 10.1097/00000539-199908000-00063. No abstract available.
- Background: PubMed 11915061Hogan Q. Distribution of solution in the epidural space: examination by cryomicrotome section. Reg Anesth Pain Med. 2002 Mar-Apr;27(2):150-6. doi: 10.1053/rapm.2002.29748.
- Background: PubMed 11454372Comparative Obstetric Mobile Epidural Trial (COMET) Study Group UK. Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial. Lancet. 2001 Jul 7;358(9275):19-23. doi: 10.1016/S0140-6736(00)05251-X.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Feyce Peralta, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Low volume bolus and High volume bolus in people with Pain and Anesthesia, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anesthesia Provider Administered Bolus (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03553576, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2025.