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Oliceridine in Patients With Acute Burn Injuries (RELIEVE)

Primary Purpose

Acute Pain, Burns, Adverse Drug Event

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Oliceridine
Historical opioid use
Sponsored by
University of Tennessee
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Pain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Regional One HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Oliceridine Arm

Historical control

Arm Description

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.

Retrospective, observational, historical control arm matched by age, TBSA, number of surgeries, and opioid and illicit drug use histories

Outcomes

Primary Outcome Measures

Analyze change in pain scores after initiation of oliceridine in patients with moderate or severe pain after acute burn injury
Change in Numeric Rating Scale (0 - 10 with 10 being the worst) pain scores after initiation

Secondary Outcome Measures

Characterize adverse events associated with administration of oliceridine in patients with acute burn injury
Monitor for adverse events
Establish a burn injury-specific half maximal effective concentration
Plasma samples to measure concentration and pair with numeric pain score captured for Outcome 1
Establish a burn injury-specific half-life
Plasma samples to measure concentrations and calculate elimination coefficient
Establish a burn injury-specific volume of distribution
Plasma samples to measure concentrations and calculate volume of distribution

Full Information

First Posted
June 22, 2022
Last Updated
May 17, 2023
Sponsor
University of Tennessee
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1. Study Identification

Unique Protocol Identification Number
NCT05465226
Brief Title
Oliceridine in Patients With Acute Burn Injuries
Acronym
RELIEVE
Official Title
A pRospective, Case-controlled Evaluation of oLIceridine for Moderate or sEVEre Pain in Patients With Acute Burn Injuries. (RELIEVE)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2023 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Tennessee

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Pain, Burns, Adverse Drug Event, Respiratory Depression, Nausea and Vomiting, Postoperative

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
The study will be a single-center, prospective, case-controlled trial. Intervention arm patients will be randomly matched 2:1 to a historical comparator, based on age, TBSA, number of surgeries, and opioid and illicit drug use histories
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Oliceridine Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Historical control
Arm Type
Active Comparator
Arm Description
Retrospective, observational, historical control arm matched by age, TBSA, number of surgeries, and opioid and illicit drug use histories
Intervention Type
Drug
Intervention Name(s)
Oliceridine
Intervention Description
see arm description
Intervention Type
Drug
Intervention Name(s)
Historical opioid use
Intervention Description
Historical matched, control group in 2:1 ratio
Primary Outcome Measure Information:
Title
Analyze change in pain scores after initiation of oliceridine in patients with moderate or severe pain after acute burn injury
Description
Change in Numeric Rating Scale (0 - 10 with 10 being the worst) pain scores after initiation
Time Frame
Baseline and every 3-4 hours as standard of care allows or study medication continued, up to 7 days
Secondary Outcome Measure Information:
Title
Characterize adverse events associated with administration of oliceridine in patients with acute burn injury
Description
Monitor for adverse events
Time Frame
At least daily while taking study medication, up to 7 days
Title
Establish a burn injury-specific half maximal effective concentration
Description
Plasma samples to measure concentration and pair with numeric pain score captured for Outcome 1
Time Frame
Sparse sampling strategy with up to 6 samples taken over the 4-hour dosing scheme
Title
Establish a burn injury-specific half-life
Description
Plasma samples to measure concentrations and calculate elimination coefficient
Time Frame
Sparse sampling strategy with up to 6 samples taken over the 4-hour dosing scheme
Title
Establish a burn injury-specific volume of distribution
Description
Plasma samples to measure concentrations and calculate volume of distribution
Time Frame
Sparse sampling strategy with up to 6 samples taken over the 4-hour dosing scheme

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David M Hill, PharmD
Phone
(901) 545-8011
Email
dmhill@regionalonehealth.org
First Name & Middle Initial & Last Name or Official Title & Degree
Yvonne Shaw, RN
Phone
(901) 448-2714
Email
yshaw@uthsc.edu
Facility Information:
Facility Name
Regional One Health
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yvonne Shaw, RN
Email
yshaw@uthsc.edu
First Name & Middle Initial & Last Name & Degree
David M. Hill, PharmD
First Name & Middle Initial & Last Name & Degree
S. Ram Velamuri, MD

12. IPD Sharing Statement

Plan to Share IPD
No
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Oliceridine in Patients With Acute Burn Injuries

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