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

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

Detailed Description
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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.

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

Conditions
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Pregnancy Related

Intervention / Treatment
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* Drug: Clonidine
* Drug: Dexmedetomidine
* Drug: Fentanyl
* Drug: Ropivacaine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is designed as a randomized, quadruple blinded, parallel arm, controlled, non-inferiority trial in 3 groups allocated in a 1:1:1 ratio
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy, Vaginal Delivery, Epidural Labor Analgesia