Clinical trial NCT05487196: Effectiveness of Clonidine, Dexmedetomidine, and Fentanyl Adjuncts for Labor Epidural Analgesia
Official title: Effectiveness of Clonidine, Dexmedetomidine, and Fentanyl Adjuncts for Labor Epidural Analgesia: A Randomized Controlled Quadruple Blinded Non-Inferiority Trial (CLASSIER Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pregnancy Related
Keywords: Pregnancy
Vaginal Delivery
Epidural Labor Analgesia
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2022-08-04
Enrollment: 88
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pain Burden, AUC (30 Minutes)
timeFrame: First 30 minutes of analgesia
Secondary outcomes:
measure: Pain Burden, AUC (120 Minutes)
timeFrame: First 120 minutes of analgesia
measure: Pain Scores
timeFrame: 15 minutes after initiation of epidural analgesia
measure: Pain Scores
timeFrame: 30 minutes after initiation of epidural analgesia
measure: Pain Scores
timeFrame: Immediately after delivery
measure: Cesarean Delivery
timeFrame: At the time of delivery
measure: Hypotension
timeFrame: Between 0-120 min after study drug administration
measure: Nausea
timeFrame: 0-120 min after study drug administration
measure: Vomiting
timeFrame: 0-120 min after study drug administration
measure: Shivering
timeFrame: 0-120 min after study drug administration
measure: Pruritus
timeFrame: 0-120 min after study drug administration
measure: Patient Treatment Satisfaction
timeFrame: Immediately after delivery
measure: Newborn Apgar Score
timeFrame: 1 minute after delivery
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Magee-Womens Hospital
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Grace Lim, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: