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

Effectiveness of Clonidine, Dexmedetomidine, and Fentanyl Adjuncts for Labor Epidural Analgesia: A Randomized Controlled Quadruple Blinded Non-Inferiority Trial (CLASSIER Trial)

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

Study Overview

• Status: Completed
• Conditions: Pregnancy Related
• Intervention / Treatment: Drug: Clonidine; Drug: Ropivacaine; Drug: Dexmedetomidine; Drug: Fentanyl

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.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amy Monroe, MPH, MBA; Phone Number: 412-623-6382; Email: Monroeal@upmc.edu
• Study Contact Backup: Name: Carly Riedmann, BS; Phone Number: 412-623-4147; Email: riedmannca@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Magee-Womens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clonidine; Bolus dose at epidural initiation, through the epidural catheter: 10 ml Ropivacaine 0.1 % combined with a single dose of Clonidine 60 mcg	Drug: Clonidine; Clonidine belongs to the drug classification of antihypertensives; Drug: Ropivacaine; Ropivacaine belongs to the drug classification of local or regional anesthesia for surgery and is used as standard of care
Experimental: Dexmedetomidine; Bolus dose at epidural initiation, through the epidural catheter: 10 ml Ropivacaine 0.1 % combined with a single dose of Dexmedetomidine 30 mcg	Drug: Ropivacaine; Ropivacaine belongs to the drug classification of local or regional anesthesia for surgery and is used as standard of care; Drug: Dexmedetomidine; Dexmedetomidine belongs to the drug classification of sedatives
Active Comparator: Ropivacaine + Fentanyl; Bolus dose at epidural initiation, through the epidural catheter: 10 ml Ropivacaine 0.1 % combined with a single dose of Fentanyl 100mcg	Drug: Ropivacaine; Ropivacaine belongs to the drug classification of local or regional anesthesia for surgery and is used as standard of care; Drug: Fentanyl; Fentanyl belongs to the drug classification of analgesic opioid agonists and is used as the standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Burden, AUC (30 minutes)	Pain score area under the curve (AUC) where pain scores are measured from 0 (no pain) to 10 (worst imaginable pain), for the duration of epidural analgesia. Pain AUC will be compared between Fentanyl, Clonidine and Dexmedetomidine groups.	First 30 minutes of analgesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Scores (30 minutes)	Average (and standard deviations) pain scores within each of the three medication groups. Pain scores are measured from 0 (no pain) to 10 (worst imaginable pain). Pain scores will be compared between Fentanyl, Clonidine and Dexmedetomidine groups.	30 minutes after initiation of epidural analgesia
Pain Burden, AUC (120 minutes)	Pain score area under the curve (AUC) where pain scores are measured from 0 (no pain) to 10 (worst imaginable pain), for the duration of epidural analgesia. Pain AUC will be compared between Fentanyl, Clonidine and Dexmedetomidine groups.	First 120 minutes of analgesia

Collaborators and Investigators

• Sponsor: Grace Lim, MD, MS
• Investigators: Principal Investigator: Grace Lim, MD, MS, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2022
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Pregnancy; Vaginal Delivery; Epidural Labor Analgesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anesthetics, Local; Sympatholytics; Fentanyl; Dexmedetomidine; Ropivacaine; Clonidine
• Other Study ID Numbers: STUDY22030095

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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