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

April 9, 2025 updated by: Grace Lim, MD, MS

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
88

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Pregnant minors were not enrolled in this trial.

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pain Burden, AUC (30 Minutes)
Time Frame: 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.
First 30 minutes of analgesia

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pain Burden, AUC (120 Minutes)
Time Frame: 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.
First 120 minutes of analgesia
Pain Scores
Time Frame: 15 minutes after initiation of epidural analgesia
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.
15 minutes after initiation of epidural analgesia
Pain Scores
Time Frame: 30 minutes after initiation of epidural analgesia
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.
30 minutes after initiation of epidural analgesia
Pain Scores
Time Frame: Immediately 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.
Immediately after delivery
Cesarean Delivery
Time Frame: At 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.
At the time of delivery
Hypotension
Time Frame: Between 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.
Between 0-120 min after study drug administration
Nausea
Time Frame: 0-120 min after study drug administration
Patient self-report of nausea at any time between 0-120 min after study drug administration
0-120 min after study drug administration
Vomiting
Time Frame: 0-120 min after study drug administration
Patient self-report of vomiting at any time between 0-120 min after study drug administration
0-120 min after study drug administration
Shivering
Time Frame: 0-120 min after study drug administration
Patient self-report of shivering at any time between 0-120 min after study drug administration
0-120 min after study drug administration
Pruritus
Time Frame: 0-120 min after study drug administration
Patient self-report of pruritus at any time between 0-120 min after study drug administration
0-120 min after study drug administration
Patient Treatment Satisfaction
Time Frame: Immediately after delivery
Patient self-report regarding satisfaction with analgesia on a scale of 1-10; 1 = not satisfied, 10 = the most satisfied.
Immediately after delivery
Newborn Apgar Score
Time Frame: 1 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.
1 minute after delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Grace Lim, MD, MS

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Grace Lim, MD, MS, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 28, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 2, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 2, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 4, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 27, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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