Oliceridine in Patients With Acute Burn Injuries (RELIEVE)

October 24, 2023 updated by: University of Tennessee

A pRospective, Case-controlled Evaluation of oLIceridine for Moderate or sEVEre Pain in Patients With Acute Burn Injuries. (RELIEVE)

Pain after acute burn injury is complex with much still not understood. The primary mechanism is believed to be nociceptive, but is interwoven with aspects of somatogenic, neuropathic, and psychogenic pathways. As such, opioid receptor agonists are an essential component for pain management after burn injury. The majority of wound care and dressing changes are completed in non-intubated patients and rates of respiratory depression concerning. Oliceridine is a biased, selective MOR agonist approved for treatment of acute pain. To date there is no literature of use in patients with burn injuries. While it should be effective, efficacy and the potential for reduced adverse events need to be quantified. Current practice and guidelines, plead for better analgesia for patients with burn injuries.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Pain after acute burn injury is complex with much still not understood. After acute burn injury, both injured tissue and adjacent non-burned tissue, upregulate response to painful and non-painful stimulus (hyperalgesia and allodynia, respectively). The primary mechanism is believed to be nociceptive, but is interwoven with aspects of somatogenic, neuropathic, and psychogenic pathways. As such, opioid receptor agonists are an essential component for pain management after burn injury. Currently, high-dose fentanyl, oxycodone, hydromorphone, and morphine are used at profound doses to mitigate pain associated with daily care of patients with burn injuries. The majority of wound care and dressing changes are completed in non-intubated patients and rates of respiratory depression concerning.

High-quality data is controversial or lacking on the best approach for multimodal analgesia. Additionally, limitations exist for prescribing and monitoring some agents. While a multimodal approach may lead to a reduction in acute or chronic pain, adding a handful of medicines to eliminate a single agent leads to exponentially more side effects, risk of adverse effects, drug interactions, and pill burden. Drugs targeting neuropathic pain delay neural processing and are accompanied by cognitive slowing and responsiveness, which increases fall risk and limits rehabilitation participation. Gabapentin and pregabalin efficacies are highly debated with variable dosing recommendations. Side effects are common and include dizziness, somnolence, confusion, vision loss, respiratory dysfunction, peripheral edema, gastrointestinal discomfort or irregularities, or asthenia. If effective, serotonin-norepinephrine reuptake inhibitors response can be delayed by weeks and are known to cause significant weight loss, dizziness, asthenia, sleep disorders, and gastrointestinal dysfunction. Acetaminophen can help reduce background pain, but is hepatotoxic, depletes glutathione, and can mask fever. Nonsteroidal anti-inflammatory drugs carry significant safety concerns, including cardiovascular events, platelet dysfunction, bleeding, gastrointestinal toxicity, and renal failure. Local anesthetics have limited efficacy and dissipate quickly. Peripheral nerve blocks have mostly been studied for donor site pain, and placement requires specialized skills. Ketamine can be extremely helpful, especially in non-naïve patients with high-opioid tolerances but is approved as a moderate sedative and many state laws limit who can prescribe and/or monitor its administration. While ketamine does not depress respiratory drive, it is a hallucinogen, pro-deliriogenic, pro-arrhythmogenic, and carries its own concerns for gastrointestinal irregularities and drug dependence.

Opioid agonists bind to the mu opioid receptor (MOR), triggering downstream signaling through either G-protein-coupled or β-arrestin pathways. While the G-protein pathway is primarily involved in analgesia, β-arrestin has been shown responsible for adverse events, especially respiratory depression and gastrointestinal dysfunction. Additionally, the β-arrestin pathway terminates G-protein activation and induces endocytosis of the receptor, which can lead to reduced analgesia or opioid tolerance. Oliceridine is a biased, selective MOR agonist approved for treatment of acute pain. Oliceridine has shown a 3-fold preferential pathway activation of G-protein over β-arrestin. As a result, subsequent clinical trials have resulted in improved analgesia over placebo and morphine, while significantly reducing adverse events. To date there is no literature of use in patients with burn injuries. While it should be effective, efficacy and the potential for reduced adverse events need to be quantified. Current practice and guidelines, plead for better analgesia for patients with burn injuries.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 4

Contacts and Locations

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

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38103
        • Regional One Health

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1) age ≥ 18 years old,
  • 2) total body surface area (TBSA) burned < 20%
  • 3) deep partial thickness or full thickness burns admitted for possible or definitive surgical needs,
  • 4) moderate or severe pain related to acute burns (NRS ≥ 4 out of 10)

Exclusion Criteria:

  • 1) Presence of inhalation injury,
  • 2) Pregnant,
  • 3) Incarcerated,
  • 4) only initial admission,
  • 5) known anaphylaxis to oliceridine or other opioids,
  • 6) Patient or authorized representative unable or unwilling to consent,
  • 7) known cocaine, methamphetamine, or opioid use history,
  • 8) use of numeric rating scale (NRS) would be inaccurate or inappropriate
  • 9) Significant hepatic dysfunction

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oliceridine Arm
Initially, patients will receive oliceridine 1-3 mg IVP every 1-3 hours as needed for moderate or severe pain (NRS ≥ 4) with 1-3 mg every 1-3 hours for breakthrough pain. NRS will be assessed every 3-4 hours routinely. Rescue doses will be allowed per clinical discretion as oliceridine 1-3 mg every hour. Doses will be titrated according to patient response and clinical discretion. In settings where rapid analgesia is needed, such as the operating room, post-anesthesia care unit, emergency room, or hydrotherapy, oliceridine will be administered in 0.5-2 mg doses every 5 minutes as needed for moderate or severe pain, according to anesthesiologist or treating physician's discretion. For the purposes of the study oliceridine will not exceed 7 days of administration and patients will be transitioned from intravenous opioids to oral therapy and de-escalated from opioids, as soon as the team deems appropriate.
Drug: Oliceridine
see arm description
Active Comparator: Historical control
Retrospective, observational, historical control arm matched by age, TBSA, number of surgeries, and opioid and illicit drug use histories
Drug: Historical opioid use
Historical matched, control group in 2:1 ratio

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Analyze change in pain scores after initiation of oliceridine in patients with moderate or severe pain after acute burn injury
Time Frame: Baseline and every 3-4 hours as standard of care allows or study medication continued, up to 7 days
Change in Numeric Rating Scale (0 - 10 with 10 being the worst) pain scores after initiation
Baseline and every 3-4 hours as standard of care allows or study medication continued, up to 7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterize adverse events associated with administration of oliceridine in patients with acute burn injury
Time Frame: At least daily while taking study medication, up to 7 days
Monitor for adverse events
At least daily while taking study medication, up to 7 days
Establish a burn injury-specific half maximal effective concentration
Time Frame: Sparse sampling strategy with up to 6 samples taken over the 4-hour dosing scheme
Plasma samples to measure concentration and pair with numeric pain score captured for Outcome 1
Sparse sampling strategy with up to 6 samples taken over the 4-hour dosing scheme
Establish a burn injury-specific half-life
Time Frame: Sparse sampling strategy with up to 6 samples taken over the 4-hour dosing scheme
Plasma samples to measure concentrations and calculate elimination coefficient
Sparse sampling strategy with up to 6 samples taken over the 4-hour dosing scheme
Establish a burn injury-specific volume of distribution
Time Frame: Sparse sampling strategy with up to 6 samples taken over the 4-hour dosing scheme
Plasma samples to measure concentrations and calculate volume of distribution
Sparse sampling strategy with up to 6 samples taken over the 4-hour dosing scheme

Collaborators and Investigators

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

Sponsor

University of Tennessee

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

April 1, 2023

Primary Completion (Actual)

September 30, 2023

Study Completion (Actual)

October 24, 2023

Study Registration Dates

First Submitted

June 22, 2022

First Submitted That Met QC Criteria

July 14, 2022

First Posted (Actual)

July 19, 2022

Study Record Updates

Last Update Posted (Actual)

October 26, 2023

Last Update Submitted That Met QC Criteria

October 24, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22-08748-FB

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.

Yes

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.

Clinical Trials on Burns

Clinical Trials on Oliceridine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Paraguay

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe