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Comparison of Epidural Fentanyl and Clonidine for Breakthrough Pain

Comparison of Fentanyl-bupivacaine and Clonidine-bupivacaine for Breakthrough Pain in Advanced Labor in Patients With Continuous Epidural Analgesia

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01846221
Enrollment
101
Registered
2013-05-03
Start date
2014-07-15
Completion date
2017-01-20
Last updated
2018-05-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Labor Pain

Keywords

Analgesia, Epidural, Pregnancy, Labor, Clonidine, Fentanyl, Bupivacaine, Childbirth

Brief summary

Epidural analgesia has proven to be an effective method for severe pain relief associated with labor and delivery. During labor, a low dose continuous infusion of local anesthetic and narcotic will be administered through an epidural catheter. As labor progresses and the baby's head makes it way through the pelvis, breakthrough pain may emerge and often needs further treatment. The investigators provide pain relief by administering analgesics through the epidural catheter. The patients will be randomly assigned to receive one of two medication mixtures believed to be successful in treating this type of pain associated with advanced labor. After this initial treatment, if pain relief is not attained, the patient may receive the other medication as well. The medications used in this study have been used at this institution for some time and have been found to be safe for mother and baby. The opioid (fentanyl) dose is small and only a small fraction will be transmitted to the baby. The other medication (clonidine) better known as a blood pressure medication has also been used for pain relief. Studies and clinical experience have shown that clonidine when given epidurally in the doses used in this study has minimal, if any effect, on the blood pressure of the mother or of the baby. The investigators will record medical and obstetric history and labor progress relevant to the patient. The patient will be asked questions regarding labor pain and side effects before and after the analgesic is administered. The primary objective is to determine which treatment regimen is more successful in abolishing breakthrough pain in advanced labor.

Detailed description

Epidural analgesia is a popular choice among patients for relief of severe pain associated with labor and delivery. Currently, at the investigators' institution the investigators use a continuous infusion of low dose local anesthetic and narcotic (12 ml/hr of 0.0625% bupivacaine with 2 micrograms/ml fentanyl) after the initial spinal or epidural dose to maintain patient comfort until delivery. This dose of the infusion is chosen because it often provides adequate comfort without interfering with the mobility of the patient and her ability to effectively push during delivery. However, this low-dose epidural infusion strategy often results in recurrence of pain after an initial pain-free period. This recurring pain is known as breakthrough pain and is alleviated by administering small boluses of analgesics via the epidural catheter. The pain occurring in labor is initially of visceral origin and is mediated by pain fibers originating from the low thoracic and upper lumbar segments of the spinal cord. As labor progresses to the late first phase (also known as transitional stage), pain sensations originating from the distension of the pelvic floor, vagina and perineum adds a somatic component to labor pain. This type of breakthrough pain, mediated by nerve fibers originating from the sacral nerves at dermatomes S2-S4, is often difficult to treat. Patients may experience inadequate analgesia even after boluses of analgesics are administered. Inadequate analgesia is deleterious due to subjective discomfort with its associated neurohumoral and physiological changes, and can be an initiator of the urge to bear down (push). Pushing before complete dilation of the cervix may lead to swelling, cervical injury and premature exhaustion of the mother. Adequate pain control will allow the cervix to fully dilate and motivate the mother to push effectively at the appropriate time. Although requests from patients to alleviate late stage breakthrough pain are common, there are no established data in the literature regarding the most effective strategy for pain management in this stage of labor. This study is designed to compare the efficacy of two treatments for controlling late first stage breakthrough pain during labor: clonidine-bupivacaine versus fentanyl-bupivacaine. Both strategies are used at Columbia University Medical Center (CUMC) in this clinical situation, and there is no clear evidence whether one is superior.

Interventions

DRUGClonidine

Subjects randomized to clonidine will receive a mixture of 100 micrograms clonidine and 12.5 mg bupivacaine 10 ml of volume.

DRUGFentanyl

Subjects randomized to fentanyl will receive 100 mcg fentanyl and 12.5 mg bupivacaine in 10 ml of volume.

Sponsors

Columbia University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Group assignment will be performed by opening a previously prepared numbered opaque envelope containing the assignment CLO or FENT. The investigator preparing the study drug will not reveal the group assignment. The investigator administering the drug (different from the investigator preparing the drug) and assessing the outcomes will be blinded to the group assignment. The participant will also be blinded to the group assignment.

Intervention model description

Subjects will randomly receive either a mixture of 100 mcg of clonidine and 12.5 mg of bupivacaine for a total volume of 10 ml (CLON group) and the other group will receive 100 mcg of fentanyl and 12.5 mg of bupivacaine for a total volume of 10 ml (FENT group). If the treatment is declared a failure, the patient will receive the alternative of the initial treatment.

Eligibility

Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* women in labor at term pregnancy * healthy * epidural analgesia in place * breakthrough pain in advanced labor

Exclusion criteria

* chronic pain syndrome * receiving systemic opioids within 4 hours * receiving chronic antidepressants, clonidine, opioids

Design outcomes

Primary

MeasureTime frameDescription
Number of Subjects With Success Rate at 15 Minutes Post-epidural Bolus InjectionBaseline, 15 Minutes post epidural administrationPain Visual Analogue Scale (VAS) was evaluated every 5 min for 15 min. 'Success' is defined as at least a 4-point reduction in VAS at 15 min. (0=no pain, 10= worst pain)

Secondary

MeasureTime frameDescription
Maternal Systolic Blood PressureBaseline, 30 Minutes post epidural administrationBlood pressure will be measured at different timepoints.
Maternal Heart RateBaseline, 30 Minutes post epidural administrationHeart rate will be measured at different timepoints.
Neonatal Apgar Score1 minute and 5 minutes post deliveryThe Apgar score is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth. A score of 7, 8, or 9 is normal and is a sign that the newborn is in good health.
Number of Spontaneous Vaginal DeliveriesUpon delivery (approximately up to 8 hours from baseline)Mode of delivery: spontaneous vaginal or instrumental vaginal versus cesarean.

Countries

United States

Participant flow

Participants by arm

ArmCount
Clonidine
Participants randomized to this arm of the study receive 100 micrograms clonidine with the bupivacaine in their epidural when requesting pain relief in advanced labor Clonidine: Subjects randomized to clonidine will receive a mixture of 100 micrograms clonidine and 12.5 mg bupivacaine 10 ml of volume.
47
Fentanyl
Participants randomized to this arm of study will receive 100 mcg fentanyl with the bupivacaine in their epidural when requesting pain relief in advanced labor Fentanyl: Subjects randomized to fentanyl will receive 100 mcg fentanyl and 12.5 mg bupivacaine in 10 ml of volume.
51
Total98

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAge Exclusion10
Overall StudyCatheter Failure20

Baseline characteristics

CharacteristicClonidineFentanylTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
47 Participants51 Participants98 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
3 Participants3 Participants6 Participants
Race (NIH/OMB)
Black or African American
16 Participants10 Participants26 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants7 Participants8 Participants
Race (NIH/OMB)
White
27 Participants31 Participants58 Participants
Region of Enrollment
United States
47 participants51 participants98 participants
Sex: Female, Male
Female
47 Participants51 Participants98 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 470 / 51
other
Total, other adverse events
0 / 470 / 51
serious
Total, serious adverse events
0 / 470 / 51

Outcome results

Primary

Number of Subjects With Success Rate at 15 Minutes Post-epidural Bolus Injection

Pain Visual Analogue Scale (VAS) was evaluated every 5 min for 15 min. 'Success' is defined as at least a 4-point reduction in VAS at 15 min. (0=no pain, 10= worst pain)

Time frame: Baseline, 15 Minutes post epidural administration

Population: 3 subjects in the Clonidine group were not included in the analysis due to the following reasons: 2 catheter failures, 1 age exclusion.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
ClonidineNumber of Subjects With Success Rate at 15 Minutes Post-epidural Bolus Injection31 Participants
FentanylNumber of Subjects With Success Rate at 15 Minutes Post-epidural Bolus Injection38 Participants
p-value: 0.38ANOVA
Secondary

Maternal Heart Rate

Heart rate will be measured at different timepoints.

Time frame: Baseline, 30 Minutes post epidural administration

Population: 48 out of 51 participants were included from the Fentanyl group due to 4 participants did not have heart rate taken at 30 minutes.

ArmMeasureGroupValue (MEAN)
ClonidineMaternal Heart RateBaseline87 beats per minute (BPM)
ClonidineMaternal Heart Rate30 Minutes84 beats per minute (BPM)
FentanylMaternal Heart RateBaseline84 beats per minute (BPM)
FentanylMaternal Heart Rate30 Minutes85 beats per minute (BPM)
Secondary

Maternal Systolic Blood Pressure

Blood pressure will be measured at different timepoints.

Time frame: Baseline, 30 Minutes post epidural administration

Population: 46 out of 47 participants were included from the Clonidine group due to 1 participant did not have blood pressure taken at 30 minutes. 48 out of 51 participants were included from the Fentanyl group due to 3 participants did not have blood pressure taken at 30 minutes.

ArmMeasureGroupValue (MEAN)
ClonidineMaternal Systolic Blood PressureBaseline123 mm Hg
ClonidineMaternal Systolic Blood Pressure30 Minutes116 mm Hg
FentanylMaternal Systolic Blood PressureBaseline121 mm Hg
FentanylMaternal Systolic Blood Pressure30 Minutes118 mm Hg
Secondary

Neonatal Apgar Score

The Apgar score is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth. A score of 7, 8, or 9 is normal and is a sign that the newborn is in good health.

Time frame: 1 minute and 5 minutes post delivery

ArmMeasureGroupValue (MEAN)
ClonidineNeonatal Apgar Score1 Minute8.53 Apgar score
ClonidineNeonatal Apgar Score5 Minutes8.94 Apgar score
FentanylNeonatal Apgar Score1 Minute8.24 Apgar score
FentanylNeonatal Apgar Score5 Minutes8.88 Apgar score
Secondary

Number of Spontaneous Vaginal Deliveries

Mode of delivery: spontaneous vaginal or instrumental vaginal versus cesarean.

Time frame: Upon delivery (approximately up to 8 hours from baseline)

ArmMeasureValue (NUMBER)
ClonidineNumber of Spontaneous Vaginal Deliveries38 spontaneous vaginal deliveries
FentanylNumber of Spontaneous Vaginal Deliveries40 spontaneous vaginal deliveries

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026