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Comparison of Epidural Fentanyl and Clonidine for Breakthrough Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01846221
Recruitment Status : Completed
First Posted : May 3, 2013
Results First Posted : May 3, 2018
Last Update Posted : May 3, 2018
Information provided by (Responsible Party):
Allison Lee, Columbia University

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.

Condition or disease Intervention/treatment Phase
Labor Pain Drug: Clonidine Drug: Fentanyl Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 101 participants
Allocation: Randomized
Intervention Model: Parallel 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.
Masking: Quadruple (Participant, Care Provider, 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.
Primary Purpose: Treatment
Official Title: Comparison of Fentanyl-bupivacaine and Clonidine-bupivacaine for Breakthrough Pain in Advanced Labor in Patients With Continuous Epidural Analgesia
Actual Study Start Date : July 15, 2014
Actual Primary Completion Date : January 20, 2017
Actual Study Completion Date : January 20, 2017

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 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
Drug: Clonidine
Subjects randomized to clonidine will receive a mixture of 100 micrograms clonidine and 12.5 mg bupivacaine 10 ml of volume.
Other Name: DuraClon

Experimental: 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
Drug: Fentanyl
Subjects randomized to fentanyl will receive 100 mcg fentanyl and 12.5 mg bupivacaine in 10 ml of volume.
Other Name: Sublimaze

Primary Outcome Measures :
  1. Number of Subjects With Success Rate at 15 Minutes Post-epidural Bolus Injection [ Time Frame: Baseline, 15 Minutes post epidural administration ]
    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)

Secondary Outcome Measures :
  1. Maternal Systolic Blood Pressure [ Time Frame: Baseline, 30 Minutes post epidural administration ]
    Blood pressure will be measured at different timepoints.

  2. Maternal Heart Rate [ Time Frame: Baseline, 30 Minutes post epidural administration ]
    Heart rate will be measured at different timepoints.

  3. Neonatal Apgar Score [ Time Frame: 1 minute and 5 minutes post delivery ]
    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.

  4. Number of Spontaneous Vaginal Deliveries [ Time Frame: Upon delivery (approximately up to 8 hours from baseline) ]
    Mode of delivery: spontaneous vaginal or instrumental vaginal versus cesarean.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01846221

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United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
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Principal Investigator: Allison Lee, MD Columbia University
  Study Documents (Full-Text)

Documents provided by Allison Lee, Columbia University:
Additional Information:
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Responsible Party: Allison Lee, Assistant Professor of Clinical Anesthesiology, Columbia University Identifier: NCT01846221    
Other Study ID Numbers: AAAL4101
First Posted: May 3, 2013    Key Record Dates
Results First Posted: May 3, 2018
Last Update Posted: May 3, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Allison Lee, Columbia University:
Additional relevant MeSH terms:
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Labor Pain
Breakthrough Pain
Neurologic Manifestations
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Antihypertensive Agents
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action