Breakthrough PainNCT06494280
PIEB Compared With CEI on Breakthrough Pain in Nulliparous Women
A study testing programmed intermittent Bolus epidural analgesia and continuous epidural infusion in people with Breakthrough Pain, run by Holy Family Hospital, Nazareth, Israel at 1 site in Israel.
Trial summary
The goal of this randomized controlled trial is to examine the impact of programmed intermittent bolus epidural analgesia technique on the incidence of breakthrough pain during labor in nulliparous women compared to continuous epidural infusion. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breakthrough Pain
- What is being tested?
- programmed intermittent Bolus epidural analgesia and continuous epidural infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteIsrael
- Study dates
- 10 Sep 2024to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Nulliparous women
- Term pregnancy
- Singleton
- Vertex presentation
- Latent phase (cervical dilatation <6 cm)
- Epidural analgesia request
- Visual Analogue Scale score > 40
Who cannot join
- Estimated fetal weight > 4 kg
- Intra uterine fetal death
- Drug sensitivity
- Anomalous fetus
- Contraindication for epidural analgesia
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Holy Family Hospital
Nazareth
Raed Salim, MD, r.salim@hfhosp.org
Asmaa Masri Esmail, MD
About this study
Official title: Impact of Programmed Intermittent Epidural Bolus Compared With Continuous Epidural Infusion on Breakthrough Pain Among Laboring Nulliparous Women. A Randomized Controlled Trial
The goal of this randomized controlled trial is to examine the impact of programmed intermittent bolus epidural analgesia technique on the incidence of breakthrough pain during labor in nulliparous women compared to continuous epidural infusion.
Nulliparous women will randomly be divided during labor into two groups; study group will receive mix of Bupivacaine and fentanyl once (bolus) every 60 minutes; the control group will receive continuously the same dose during an hour, until delivery.
Read the detailed description
There are several pharmacological and non-pharmacological techniques for pain relief during labor. Epidural analgesia is considered the most effective modality for intrapartum pain relief.
Maintenance of epidural analgesia is achieved by different techniques; continuous epidural infusion (CEI), intermittent epidural analgesia (IEA), patient control epidural analgesia (PCEA) and combination between the techniques.
Another technique, the Programmed Intermittent Bolus Epidural Analgesia (PIBEA). The advantage of this technique is that boluses are given all the time at planned intervals, so laboring women do not depend on the medical staff to receive the bolus when there is a breakthrough pain.
This method has been reported to be associated with less motor block, lower incidence of instrumental vaginal deliveries, and less consumption of anesthetic agents when compared to CEI. There are no conclusive data regarding the use of PIBEA in combination with PCEA compared to CEI and PCEA on the effect of pain relief during labor and birth outcomes. The hypothesis of the current trial is that PIBEA and PCEA will decrease the incidence of breakthrough pain, and probably shorten the second stage of labor, lead to fewer instrumental deliveries and higher women's satisfaction compared to CEI and PCEA.
- Conditions
- Breakthrough Pain
- Being tested
- programmed intermittent Bolus epidural analgesia, continuous epidural infusion
- Keywords
- Nullipara, Term pregnancy, Singleton, Vertex presentation, Latent phase, Maternal request for epidural, Visual analogue scale > 4
- Medical subject headings
- Breakthrough Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
programmed intermittent Bolus epidural analgesiaDrug
Also called Bupivacaine + Fentanyl
About 30 minutes after the end of the epidural and administration of the loading dose, the woman will be asked to report her pain level. If the VAS score <30, the woman will receive the study group protocol for pain maintenance, i.e., a programmed intermittent bolus of 10 ml of 0.1% bupivacaine and 2 μg/ml fentanyl every hour until the completion of labor and suturing of the incision. The participant can add to herself 5 ml of the same solution of Bupivacaine and Fentanyl every 30 minutes. The maximum dose that the parturient is allowed to receive is 20 ml for one hour.
If a breakthrough pain appears during labor, a bolus of 10 ml of anesthetic solution with the same concentration will be added.
Participants with a VAS score >30 after 30 minutes of the loading dose will be asked to perform a new epidural (if it was decided that the epidural failed) otherwise her data will not be collected for the final analysis of the study.
continuous epidural infusionDrug
Also called Bupivacaine + Fentanyl
About 30 minutes after the end of the epidural and administration of the loading dose, the woman will be asked to report her pain level. If the VAS score <30, the woman will receive the control group protocol for pain maintenance, i.e., 0.1% Bupivacaine and 2 μg/ml fentanyl as a continuous infusion per one hour, until the delivery is completed, and laceration is sutured. The participant can add to herself 5 ml of the same solution of Bupivacaine and Fentanyl every 30 minutes. The maximum dose that the parturient is allowed to receive is 20 ml for one hour.
If a breakthrough pain appears during labor, a bolus of 10 ml of anesthetic solution with the same concentration will be added.
Participants with a VAS score >30 after 30 minutes of the loading dose will be asked to perform a new epidural (if it was decided that the epidural failed) otherwise her data will not be collected for the final analysis of the study.
| Study group | Role | What they receive |
|---|---|---|
| study group | Active comparator | Epidural analgesia will be maintained by receiving programmed intermittent 10ml bolus of 0.1% Bupivacaine and 2microgram\ml Fentanyl every one hour, until the delivery is completed, and lacerations are sutured. Receives: Drug: programmed intermittent Bolus epidural analgesia |
| control group | Active comparator | Epidural analgesia will be maintained by receiving 10ml\h continuous infusion of 0.1% Bupivacaine and 2microgram\ml Fentanyl until the delivery is completed, and lacerations are sutured. Receives: Drug: continuous epidural infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
breakthrough pain
Incidence of breakthrough pain, defined as Visual Analogue Scale (VAS) score > 30.
The VAS consists of a 100cm line, with two end points representing 0 ('no pain') and 100 (severe pain).
Measured: 48 hours
Secondary outcomes (26)
manual bolus (top up)
Number of participants who will require top up of Bupivacaine and Fentanyl due to breakthrough pain.
Measured: 48 hours
Hourly visual analogue scale
Hourly pain according to visual analogue scale (VAS) score. The VAS consists of a 100cm line, with two end points representing score 0 (no pain) and score 100 (severe pain).
Measured: 48 hours
Time to delivery
Time from epidural analgesia to delivery.
Measured: 48 hours
Oxytocin augmentation
Incidence of women who will require Oxytocin for labor augmentation
Measured: 48 hours
Duration of second stage
The time from complete cervical dilatation until delivery of the fetus (minutes)
Measured: 48 hours
Intrapartum fever
Number of patients that will have intrapartum fever ≥ 38 °C
Measured: 48 hours
Number of patients that will require use of intrapartum use of antibiotic treatment.
Number of patients that will require use of intrapartum use of antibiotic treatment due to intrapartum infection.
Measured: 48 hours
Mode of delivery
Whether the birth was a normal spontaneous birth, operative vaginal birth or a cesarean section.
Measured: 48 hours
Indications for cesarean or operative vaginal deliveries
Was the reason for operative vaginal delivery or cesarean delivery due to non-progressive labor, fetal status, or a combination of both?
Measured: 48 hours
duration of third stage
time from delivery of the fetus the delivery of the placenta (minutes)
Measured: 48 hours
Early postpartum hemorrhage (PPH)
Number of Participants with develop PPH
Measured: 48 hours
Hemoglobin level
The lowest postpartum Hemoglobin level
Measured: 96 hours
Blood transfusion
Number of Participants that will need blood transfusion.
Measured: 72 hours
Obstetric anal sphincter injury
Number of Participants with that will develop 3rd and 4th degrees perineal lacerations.
Measured: 48 hours
Motor block of any leg
Incidence of motor block will be assessed according to Bromage score:
Bromage 0 = No motor block. Bromage 1 = the participant is unable to flex her hip Bromage 2 = the participant is able to flex her ankle but unable to flex her hip and knee Bromage 3 = the participant is unable to flex her hip, knee and ankle
Measured: 48 hours
Urinary retention
Participant will not be able to urinate spontaneously 6 hours after delivery
Measured: 48 hours
Dural puncture
Incidence of dural puncture during performing epidural analgesia
Measured: 48 hours
Side effects related epidural analgesia use
nausea, vomiting, and pruritis
Measured: 48 hours
mean arterial blood pressure
mean arterial blood pressure (mmHg) of the participant during labor
Measured: 48 hours
systolic blood pressure < 90mmHg
incidence of systolic blood pressure < 90 during labor
Measured: 48 hours
Bupivacaine consumption
total Bupivacaine consumption during labor (ml)
Measured: 48 hours
maternal satisfaction
participant satisfaction from labor experience from 1 to 10.
1= very dissatisfied 10 = very satisfied
Measured: 48 hours
Apgar score (0 to 10)
APGAR< 7 after 1 and 5 minutes where lower scores mean a worse outcome.
Measured: 48 hours
fetal cord artery pH
Cord artery pH <7.1
Measured: 48 hours
meconium staining
Incidence of meconium-stained amniotic fluid before delivery of the fetus
Measured: 48 hours
Neonatal sepsis
Incidence of early neonatal sepsis
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 posted10 Jul 2024
- Study start10 Sep 2024
- Primary completionNov 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breakthrough PainStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Holy Family Hospital, Nazareth, Israel
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Raed Salim, MD, Holy Family Hospital, Nazareth, Israel
- Investigators
- Raed Salim, MD, Study chair, Holy Family Hospital, Nazareth, Israel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06494280
- Sponsor's protocol ID
- 297\2024 HFH
- Status last verified
- Apr 2026
- First submitted
- 2 Jul 2024
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD that underlie results in a publication
Publications
1. American College of Obstetricians and Gynecologists. Obstetric analgesia and anesthesia. ACOG Practice Bulletin No. 209. Obstet Gynecol. 2019;133:e208-25. 2. Anim-Somuah M, Smyth RM, Cyna AM, Cuthbert A. Epidural versus non-epidural or no analgesia for pain management in labour. Cochrane Database of Systematic Reviews 2018:5;CD000331. 3. Jones L, Othman M, Dowswell T, Alfirevic Z, Gates S, Newburn M, et al. Pain management for women in labour: an overview of systematic reviews. Cochrane Database of Systematic Reviews 2012:3;CD009234. 4. George RB, Allen TK, Habib AS. Intermittent epidural bolus compared with continuous epidural infusions for labor analgesia: a systematic review and meta-analysis. Anesth Analg 2013;116:133-44. 5. Sng BL, Zeng Y, de Souza NNA, Leong WL, Oh TT, Siddiqui FJ, Assam PN, Han NR, Chan ES, Sia AT. Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour. Cochrane Database Syst Rev. 2018;5:CD011344. 6. Ferrer LE, Romero DJ, Vasquez OI, Matute EC, Van de Velde M. Effect of programmed intermittent epidural boluses and continuous epidural infusion on labor analgesia and obstetric outcomes: a randomized controlled trial. Arch Gynecol Obstet. 2017;296:915-22. 7. Ojo OA, Mehdiratta JE, Gamez BH, Hunting J, Habib AS. Comparison of programmed intermittent epidural boluses with continuous epidural infusion for the maintenance of labor analgesia: a randomized, controlled, double-blind study. Anesth Analg. 2020;130:426-35. 8. Haidl F, Arne Rosseland L, Rorvik AM, Dahl V. Programmed intermittent boluses vs continuous epidural infusion in labor using an adrenaline containing solution: A randomized trial. Acta Anaesthesiol Scand. 2020;64:1505-12. 9. Riazanova OV, Alexandrovich YS, Guseva YV, Ioscovich AM. A randomized comparison of low dose ropivacaine programmed intermittent epidural bolus with continuous epidural infusion for labour analgesia. Rom J Anaesth Intensive Care. 2019;26:25-30. 10. Fan Y, Hou W, Feng S, Mao P, Wang X, Jiang J, Yuan H, Shen X, Feng S, Li P. Programmed intermittent epidural bolus decreases the incidence of intra-partum fever for labor analgesia in primiparous women: a randomized controlled study. Arch Gynecol Obstet. 2019;300:1551-7 11. Xu J, Zhou J, Xiao H, Pan S, Liu J, Shang Y, Yao S. A systematic review and meta-analysis comparing programmed intermittent bolus and continuous infusion as the background infusion for parturient-controlled epidural analgesia. Sci Rep. 2019;9:2583. 12. Wang XX, Zhang XL, Zhang ZX, Xin ZQ, Guo HJ, Liu HY, Xiao J, Zhang YL, Yuan SZ. Programmed intermittent epidural bolus in parturients: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2022;101: e28742. 13. Bullingham A, Liang S, Edmonds E, Mathur S, Sharma S. Continuous epidural infusion vs programmed intermittent epidural bolus for labour analgesia: a prospective, controlled, before-and-after cohort study of labour outcomes. Br J Anaesth. 2018;121:432-7. 14. Lin Y, Li Q, Liu J, Yang R, Liu J. Comparison of continuous epidural infusion and programmed intermittent epidural bolus in labor analgesia. Ther Clin Risk Manag. 2016;12:1107-12. 15. Lim Y, Sia AT, Ocampo C. Automated regular boluses for epidural analgesia: a comparison with continuous infusion. Int J Obstet Anesth. 2005;14:305-9. 16. Salim R, Nachum Z, Moscovici R, Lavee M, Shalev E. Continuous compared with intermittent epidural infusion on progress of labor and patient satisfaction. Obstet Gynecol 2005;106:301-6. 17. Lim Y, Ocampo CE, Supandji M, Teoh WH, Sia AT. A randomized controlled trial of three patient-controlled epidural analgesia regimens for labor. Anesth Analg 2008;107:1968-72. 18. Capogna G, Camorcia M, Stirparo S, Farcomeni A. Programmed intermittent epidural bolus versus continuous epidural infusion for labor analgesia: the effects on maternal motor function and labor outcome. A randomized double-blind study in nulliparous women. Anesth Analg 2011;113:826-31. 19. Carvalho B, George RB, Cobb B, McKenzie C, Riley ET. Implementation of Programmed Intermittent Epidural Bolus for the Maintenance of Labor Analgesia. Anesth Analg 2016;123:965-71 20. Diez-Picazo LD, Guasch E, Brogly N, Gilsanz F. Is breakthrough pain better managed by adding programmed intermittent epidural bolus to a background infusion during labor epidural analgesia? A randomized controlled trial. Minerva Anestesiol. 2019;85:1097-104. 21. Roofthooft E, Barbé A, Schildermans J, Cromheecke S, Devroe S, Fieuws S, Rex S, Wong CA, Van de Velde M. Programmed intermittent epidural bolus vs. patient-controlled epidural analgesia for maintenance of labour analgesia: a two-centre, double-blind, randomised study. Anaesthesia. 2020;75:1635-42. 22. Sultan P, Murphy C, Halpern S, Carvalho B. The effect of low concentrations versus high concentrations of local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis. Can J Anaesth. 2013;60:840-54.
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Programmed Intermittent Epidural Bolus Compared With Continuous Epidural Infusion on Breakthrough Pain Among Laboring Nulliparous Women. A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06494280
- Acronym / sponsor ID
- 297\2024 HFH
- Conditions
- Breakthrough Pain
- Keywords
- Nullipara, Term pregnancy, Singleton, Vertex presentation, Latent phase, Maternal request for epidural, Visual analogue scale > 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Holy Family Hospital, Nazareth, IsraelUniversity, hospital or other
- Study start
- 10 Sep 2024 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 10 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this randomized controlled trial is to examine the impact of programmed intermittent bolus epidural analgesia technique on the incidence of breakthrough pain during labor in nulliparous women compared to continuous epidural infusion.
Nulliparous women will randomly be divided during labor into two groups; study group will receive mix of Bupivacaine and fentanyl once (bolus) every 60 minutes; the control group will receive continuously the same dose during an hour, until delivery.
Detailed description
There are several pharmacological and non-pharmacological techniques for pain relief during labor. Epidural analgesia is considered the most effective modality for intrapartum pain relief.
Maintenance of epidural analgesia is achieved by different techniques; continuous epidural infusion (CEI), intermittent epidural analgesia (IEA), patient control epidural analgesia (PCEA) and combination between the techniques.
Another technique, the Programmed Intermittent Bolus Epidural Analgesia (PIBEA). The advantage of this technique is that boluses are given all the time at planned intervals, so laboring women do not depend on the medical staff to receive the bolus when there is a breakthrough pain.
This method has been reported to be associated with less motor block, lower incidence of instrumental vaginal deliveries, and less consumption of anesthetic agents when compared to CEI. There are no conclusive data regarding the use of PIBEA in combination with PCEA compared to CEI and PCEA on the effect of pain relief during labor and birth outcomes. The hypothesis of the current trial is that PIBEA and PCEA will decrease the incidence of breakthrough pain, and probably shorten the second stage of labor, lead to fewer instrumental deliveries and higher women's satisfaction compared to CEI and PCEA.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| study group | Active comparator | Drug: programmed intermittent Bolus epidural analgesiaEpidural analgesia will be maintained by receiving programmed intermittent 10ml bolus of 0.1% Bupivacaine and 2microgram\ml Fentanyl every one hour, until the delivery is completed, and lacerations are sutured. |
| control group | Active comparator | Drug: continuous epidural infusionEpidural analgesia will be maintained by receiving 10ml\h continuous infusion of 0.1% Bupivacaine and 2microgram\ml Fentanyl until the delivery is completed, and lacerations are sutured. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Nulliparous women
- Term pregnancy
- Singleton
- Vertex presentation
- Latent phase (cervical dilatation <6 cm)
Key exclusion criteria (5 listed)
- Estimated fetal weight > 4 kg
- Intra uterine fetal death
- Drug sensitivity
- Anomalous fetus
- Contraindication for epidural 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 |
|---|---|---|
| programmed intermittent Bolus epidural analgesiaAlso: Bupivacaine + FentanylAbout 30 minutes after the end of the epidural and administration of the loading dose, the woman will be asked to report her pain level. If the VAS score <30, the woman will receive the study group protocol for pain maintenance, i.e., a programmed intermittent bolus of 10 ml of 0.1% bupivacaine and 2 μg/ml fentanyl every hour until the completion of labor and suturing of the incision. The participant can add to herself 5 ml of the same solution of Bupivacaine and Fentanyl every 30 minutes. The maximum dose that the parturient is allowed to receive is 20 ml for one hour. If a breakthrough pain appears during labor, a bolus of 10 ml of anesthetic solution with the same concentration will be added. Participants with a VAS score >30 after 30 minutes of the loading dose will be asked to perform a new epidural (if it was decided that the epidural failed) otherwise her data will not be collected for the final analysis of the study. | Drug | study group |
| continuous epidural infusionAlso: Bupivacaine + FentanylAbout 30 minutes after the end of the epidural and administration of the loading dose, the woman will be asked to report her pain level. If the VAS score <30, the woman will receive the control group protocol for pain maintenance, i.e., 0.1% Bupivacaine and 2 μg/ml fentanyl as a continuous infusion per one hour, until the delivery is completed, and laceration is sutured. The participant can add to herself 5 ml of the same solution of Bupivacaine and Fentanyl every 30 minutes. The maximum dose that the parturient is allowed to receive is 20 ml for one hour. If a breakthrough pain appears during labor, a bolus of 10 ml of anesthetic solution with the same concentration will be added. Participants with a VAS score >30 after 30 minutes of the loading dose will be asked to perform a new epidural (if it was decided that the epidural failed) otherwise her data will not be collected for the final analysis of the study. | Drug | control group |
Primary outcome
breakthrough pain
Time frame: 48 hours
Incidence of breakthrough pain, defined as Visual Analogue Scale (VAS) score > 30. The VAS consists of a 100cm line, with two end points representing 0 ('no pain') and 100 (severe pain).
26 secondary outcomes
manual bolus (top up)
Time frame: 48 hours
Hourly visual analogue scale
Time frame: 48 hours
Time to delivery
Time frame: 48 hours
Oxytocin augmentation
Time frame: 48 hours
Duration of second stage
Time frame: 48 hours
Intrapartum fever
Time frame: 48 hours
Number of patients that will require use of intrapartum use of antibiotic treatment.
Time frame: 48 hours
Mode of delivery
Time frame: 48 hours
Indications for cesarean or operative vaginal deliveries
Time frame: 48 hours
duration of third stage
Time frame: 48 hours
Early postpartum hemorrhage (PPH)
Time frame: 48 hours
Hemoglobin level
Time frame: 96 hours
Blood transfusion
Time frame: 72 hours
Obstetric anal sphincter injury
Time frame: 48 hours
Motor block of any leg
Time frame: 48 hours
Urinary retention
Time frame: 48 hours
Dural puncture
Time frame: 48 hours
Side effects related epidural analgesia use
Time frame: 48 hours
mean arterial blood pressure
Time frame: 48 hours
systolic blood pressure < 90mmHg
Time frame: 48 hours
Bupivacaine consumption
Time frame: 48 hours
maternal satisfaction
Time frame: 48 hours
Apgar score (0 to 10)
Time frame: 48 hours
fetal cord artery pH
Time frame: 48 hours
meconium staining
Time frame: 48 hours
Neonatal sepsis
Time frame: 72 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Results publication1. American College of Obstetricians and Gynecologists. Obstetric analgesia and anesthesia. ACOG Practice Bulletin No. 209. Obstet Gynecol. 2019;133:e208-25. 2. Anim-Somuah M, Smyth RM, Cyna AM, Cuthbert A. Epidural versus non-epidural or no analgesia for pain management in labour. Cochrane Database of Systematic Reviews 2018:5;CD000331. 3. Jones L, Othman M, Dowswell T, Alfirevic Z, Gates S, Newburn M, et al. Pain management for women in labour: an overview of systematic reviews. Cochrane Database of Systematic Reviews 2012:3;CD009234. 4. George RB, Allen TK, Habib AS. Intermittent epidural bolus compared with continuous epidural infusions for labor analgesia: a systematic review and meta-analysis. Anesth Analg 2013;116:133-44. 5. Sng BL, Zeng Y, de Souza NNA, Leong WL, Oh TT, Siddiqui FJ, Assam PN, Han NR, Chan ES, Sia AT. Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour. Cochrane Database Syst Rev. 2018;5:CD011344. 6. Ferrer LE, Romero DJ, Vasquez OI, Matute EC, Van de Velde M. Effect of programmed intermittent epidural boluses and continuous epidural infusion on labor analgesia and obstetric outcomes: a randomized controlled trial. Arch Gynecol Obstet. 2017;296:915-22. 7. Ojo OA, Mehdiratta JE, Gamez BH, Hunting J, Habib AS. Comparison of programmed intermittent epidural boluses with continuous epidural infusion for the maintenance of labor analgesia: a randomized, controlled, double-blind study. Anesth Analg. 2020;130:426-35. 8. Haidl F, Arne Rosseland L, Rorvik AM, Dahl V. Programmed intermittent boluses vs continuous epidural infusion in labor using an adrenaline containing solution: A randomized trial. Acta Anaesthesiol Scand. 2020;64:1505-12. 9. Riazanova OV, Alexandrovich YS, Guseva YV, Ioscovich AM. A randomized comparison of low dose ropivacaine programmed intermittent epidural bolus with continuous epidural infusion for labour analgesia. Rom J Anaesth Intensive Care. 2019;26:25-30. 10. Fan Y, Hou W, Feng S, Mao P, Wang X, Jiang J, Yuan H, Shen X, Feng S, Li P. Programmed intermittent epidural bolus decreases the incidence of intra-partum fever for labor analgesia in primiparous women: a randomized controlled study. Arch Gynecol Obstet. 2019;300:1551-7 11. Xu J, Zhou J, Xiao H, Pan S, Liu J, Shang Y, Yao S. A systematic review and meta-analysis comparing programmed intermittent bolus and continuous infusion as the background infusion for parturient-controlled epidural analgesia. Sci Rep. 2019;9:2583. 12. Wang XX, Zhang XL, Zhang ZX, Xin ZQ, Guo HJ, Liu HY, Xiao J, Zhang YL, Yuan SZ. Programmed intermittent epidural bolus in parturients: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2022;101: e28742. 13. Bullingham A, Liang S, Edmonds E, Mathur S, Sharma S. Continuous epidural infusion vs programmed intermittent epidural bolus for labour analgesia: a prospective, controlled, before-and-after cohort study of labour outcomes. Br J Anaesth. 2018;121:432-7. 14. Lin Y, Li Q, Liu J, Yang R, Liu J. Comparison of continuous epidural infusion and programmed intermittent epidural bolus in labor analgesia. Ther Clin Risk Manag. 2016;12:1107-12. 15. Lim Y, Sia AT, Ocampo C. Automated regular boluses for epidural analgesia: a comparison with continuous infusion. Int J Obstet Anesth. 2005;14:305-9. 16. Salim R, Nachum Z, Moscovici R, Lavee M, Shalev E. Continuous compared with intermittent epidural infusion on progress of labor and patient satisfaction. Obstet Gynecol 2005;106:301-6. 17. Lim Y, Ocampo CE, Supandji M, Teoh WH, Sia AT. A randomized controlled trial of three patient-controlled epidural analgesia regimens for labor. Anesth Analg 2008;107:1968-72. 18. Capogna G, Camorcia M, Stirparo S, Farcomeni A. Programmed intermittent epidural bolus versus continuous epidural infusion for labor analgesia: the effects on maternal motor function and labor outcome. A randomized double-blind study in nulliparous women. Anesth Analg 2011;113:826-31. 19. Carvalho B, George RB, Cobb B, McKenzie C, Riley ET. Implementation of Programmed Intermittent Epidural Bolus for the Maintenance of Labor Analgesia. Anesth Analg 2016;123:965-71 20. Diez-Picazo LD, Guasch E, Brogly N, Gilsanz F. Is breakthrough pain better managed by adding programmed intermittent epidural bolus to a background infusion during labor epidural analgesia? A randomized controlled trial. Minerva Anestesiol. 2019;85:1097-104. 21. Roofthooft E, Barbé A, Schildermans J, Cromheecke S, Devroe S, Fieuws S, Rex S, Wong CA, Van de Velde M. Programmed intermittent epidural bolus vs. patient-controlled epidural analgesia for maintenance of labour analgesia: a two-centre, double-blind, randomised study. Anaesthesia. 2020;75:1635-42. 22. Sultan P, Murphy C, Halpern S, Carvalho B. The effect of low concentrations versus high concentrations of local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis. Can J Anaesth. 2013;60:840-54.
- Individual participant dataSharing planned: Yes. IPD that underlie results in a publication
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Failing Epidural Analgesia During Labor
Failed Epidural Analgesia, Post-partum Recovery
Active, not recruitingPhase 3
Development of Variable Volume Automated Mandatory Boluses for Patient-controlled Epidural Analgesia During Labour
Labor Pain, Breakthrough Pain
Active, not recruitingPhase 3
Comparison of Regimens MPIB, CIPCEA, PCEA
Breakthrough Pain
Recruiting
Doxepin Solution for Alleviation of Stubborn Breakthrough Pain Induced by Swallowing in Patients Receiving Radiotherapy for Nasopharyngeal Carcinoma
Swallowing-induced Pain
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.
Raed Salim, MD study chair
Holy Family Hospital, Nazareth, Israel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing programmed intermittent Bolus epidural analgesia and continuous epidural infusion in people with Breakthrough Pain, run by Holy Family Hospital, Nazareth, Israel at 1 site in Israel.
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 7 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 13 Apr 2026. 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 Israel. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Raed Salim, MD (+972544986960, r.salim@hfhosp.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
breakthrough pain (time frame: 48 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 NCT06494280, which also lists 1 linked publication.
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 13 Apr 2026.