RELIEVE: Oliceridine in Patients With Acute Burn Injuries

Sponsor

University of Tennessee (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05465226

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Pain Burns Adverse Drug Event Respiratory Depression Nausea and Vomiting, Postoperative	Drug: Oliceridine Drug: Historical opioid use	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention 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 historiesThe 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)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Analyze change in pain scores after initiation of oliceridine in patients with moderate or severe pain after acute burn injury [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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Tennessee

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

University of Tennessee

ClinicalTrials.gov Identifier:

NCT05465226

Other Study ID Numbers:

22-08748-FB

First Posted:

Jul 19, 2022

Last Update Posted:

Jul 28, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Respiratory Insufficiency

Vomiting

Acute Pain

Postoperative Nausea and Vomiting

Burns

Analgesics, Opioid

Study Results

No Results Posted as of Jul 28, 2022