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Effectiveness of Clonidine, Dexmedetomidine, and Fentanyl Adjuncts for Labor Epidural Analgesia

Phase 2
Completed
Conditions
Pregnancy Related
Interventions
Registration Number
NCT05487196
Lead Sponsor
Grace Lim, MD, MS
Brief Summary

The purpose of this randomized controlled trial is to compare the effectiveness of epidural clonidine, dexmedetomidine, or fentanyl adjuncts for labor analgesia.

Detailed Description

Adjuncts for epidural labor analgesia have remained unchanged for decades, whereas changes in patient population and the opioid epidemic have created an increased demand for non-opioid alternative adjuncts to limit peripartum opioid exposure. This study aims to identify effective alternative and non-opioid adjunctive agents for epidural labor analgesia.

The opioid crisis in the United States has translated to an increasing number of pregnant women requiring care for labor and delivery. These trends have resulted in new questions about alternative epidural analgesia adjuncts besides lipophilic opioids (e.g., fentanyl and sufentanil) because: 1) many people with opioid or substance use disorder desire to avoid opioids in all formulations and routes of administration; and 2) epidural fentanyl or sufentanil administration for labor can potentially interfere with the accuracy of urine drug screening in the postpartum period, which has implications for postpartum social services considerations.

Some existing literature suggests that dexmedetomidine and clonidine are viable adjuncts to local anesthetics that offer a faster onset and a better quality of analgesia for patients requiring labor analgesia. However, the relative effectiveness of these adjunctive agents for labor analgesia have not been compared head-to-head. Better data on how these adjuncts compare with each other for labor analgesia efficacy, can result in more informed clinical care strategies.

This trial was initially initiated as a superiority design. After further scientific input, it was decided that a non-inferiority design would be more informative for the clinical question at hand. The hypothesis is that clonidine (Group C) and dexmedetomidine (Group D) are non-inferior to fentanyl (Group F) (usual care) as adjuncts for epidural labor analgesia. The null hypothesis is that clonidine and dexmedetomidine are inferior to fentanyl as adjuncts for epidural labor analgesia. Clinical Protocol specific methodology did not change throughout the trial and the full trial protocol document can be found in the relevant section below. An updated statistical analysis plan includes updated sample size calculations and has been reported to account for the noninferiority analysis plan. No data was analyzed prior to the completion of all data collection procedures.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
88
Inclusion Criteria
  • Pregnant women greater than 18 years of age
  • American Society of Anesthesiologists (ASA) Physical Status 2 or 3
  • Term pregnancy (greater than 37 gestational weeks)
  • Planning epidural labor analgesia
  • Singleton pregnancy
  • Vertex presentation
  • Planned vaginal delivery
Exclusion Criteria
  • Pre-eclampsia with or without severe features
  • New initiation of antihypertensive agent within 24 hours prior to enrollment
  • Uncontrolled systemic comorbidities [i.e., diabetes, hepatic, renal or cardiac]
  • Known or suspected fetal abnormalities
  • Allergy to study agents
  • Contra-indication to neuraxial anesthesia
  • Inability to communicate or participate in study procedures

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DexmedetomidineRopivacaineBolus dose at epidural initiation, through the epidural catheter: 10 ml Ropivacaine 0.1 % combined with a single dose of Dexmedetomidine 30 mcg
DexmedetomidineDexmedetomidineBolus dose at epidural initiation, through the epidural catheter: 10 ml Ropivacaine 0.1 % combined with a single dose of Dexmedetomidine 30 mcg
ClonidineClonidineBolus dose at epidural initiation, through the epidural catheter: 10 ml Ropivacaine 0.1 % combined with a single dose of Clonidine 60 mcg
ClonidineRopivacaineBolus dose at epidural initiation, through the epidural catheter: 10 ml Ropivacaine 0.1 % combined with a single dose of Clonidine 60 mcg
Ropivacaine + FentanylFentanylBolus dose at epidural initiation, through the epidural catheter: 10 ml Ropivacaine 0.1 % combined with a single dose of Fentanyl 100mcg
Ropivacaine + FentanylRopivacaineBolus dose at epidural initiation, through the epidural catheter: 10 ml Ropivacaine 0.1 % combined with a single dose of Fentanyl 100mcg
Primary Outcome Measures
NameTimeMethod
Pain Burden, AUC (30 Minutes)First 30 minutes of analgesia

Pain score AREA UNDER THE CURVE (AUC), which is a calculated area under curve using the trapezoidal rule, where pain scores measured from 0 (no pain) to 10 (worst imaginable pain) are on the y axis, and time is on the x axis (pain scores were measured at 5 minutes, 10 minutes,15 minutes, 30 minutes after epidural initiation for the primary outcome assessment). The scale for AUC is not 0-10 but rather is completely dependent upon the area generated under the curve created by pain scores for the first 30 minutes of epidural analgesia (primary outcome time frame): in this case, the scale is 0-250 pain units\*minute, given maximum pain score possibility of 10 and time period of 30 minutes. The units of AUC are the units of Y axis times units of X axis, in this case, pain score units \* minutes. Pain AUC was compared between Fentanyl, Clonidine and Dexmedetomidine groups.

Secondary Outcome Measures
NameTimeMethod
Patient Treatment SatisfactionImmediately after delivery

Patient self-report regarding satisfaction with analgesia on a scale of 1-10; 1 = not satisfied, 10 = the most satisfied.

Newborn Apgar Score1 minute after delivery

The Apgar score is a method of assessing newborn health at the time of delivery. Score range 0 to 10 where 0 is poor health and 10 is the best health.

Pain Burden, AUC (120 Minutes)First 120 minutes of analgesia

Pain score AREA UNDER THE CURVE (AUC), which is a calculated area under curve using the trapezoidal rule, where pain scores measured from 0 (no pain) to 10 (worst imaginable pain) are on the y axis, and time is on the x axis (pain scores were measured at 5 minutes, 10 minutes,15 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes after epidural initiation). The scale for AUC is not 0-10 but rather is completely dependent upon the area generated under the curve created by pain scores for the first 120 minutes of epidural analgesia: in this case, the scale is 0-850 pain units\*minute, given maximum pain score possibility of 10 and time period of 120 minutes. The units of AUC are the units of Y axis times units of X axis, in this case, pain score units \* minutes. Pain AUC was compared between Fentanyl, Clonidine and Dexmedetomidine groups.

Pain ScoresImmediately after delivery

Pain as defined by the Numeric Rating Score (NRS) in which the minimum score of 0 indicates no pain at all and the maximum score of 10 indicates the worst pain imaginable.

Cesarean DeliveryAt the time of delivery

This will be measured by yes/no response to cesarean delivery mode of delivery outcome. We report the raw numbers of patients who did receive a cesarean delivery according to group.

HypotensionBetween 0-120 min after study drug administration

This is measured as any hypotensive event occurring any time between 0-120 min after study drug administration.

Nausea0-120 min after study drug administration

Patient self-report of nausea at any time between 0-120 min after study drug administration

Vomiting0-120 min after study drug administration

Patient self-report of vomiting at any time between 0-120 min after study drug administration

Shivering0-120 min after study drug administration

Patient self-report of shivering at any time between 0-120 min after study drug administration

Pruritus0-120 min after study drug administration

Patient self-report of pruritus at any time between 0-120 min after study drug administration

Trial Locations

Locations (1)

UPMC Magee-Womens Hospital

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Pittsburgh, Pennsylvania, United States

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