Personalized Opiate Therapy for Post-Surgical Pain

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Tennessee Graduate School of Medicine

Disqualifiers: Cognitive impairment, Recent surgery, Allergies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a personalized approach to managing post-surgery pain by using genetic information to guide opiate therapy. The goal is to determine if tailoring pain medication based on genetic makeup can reduce long-term opioid use and improve pain control while minimizing side effects. Participants will receive either standard oxycodone treatment or hydromorphone (also known as Dilaudid or Exalgo), depending on their genetic profile. Individuals who have never used opioids and are preparing for surgery may be suitable candidates for this trial. As a Phase 4 trial, this research aims to understand how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study involves opioid-naïve patients, it is likely that you should not be on any opioid medications before participating.

What is the safety track record for hydromorphone?

Research has shown that hydromorphone is a safe choice for managing pain after surgery. Studies have found it effectively reduces pain without increasing the need for additional opioids. In one study, hydromorphone eased pain and did not lead to further opioid use.

Another study found that hydromorphone improved pain relief soon after orthopedic surgery and helped with mood and sleep issues that can occur post-surgery. Research also indicates that hydromorphone has been safely used for various types of pain, including post-surgical pain and sudden injuries.

Overall, these findings suggest that hydromorphone is well-tolerated for post-surgical pain. While every medication can have side effects, the studies do not reveal any unusual safety concerns with using hydromorphone for this purpose. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about hydromorphone for post-surgical pain because it uses a personalized approach to pain management. Unlike standard treatments like oxycodone, which are administered at fixed doses, hydromorphone dosing in this trial is guided by pharmacogenomics. This means the treatment is tailored to how well a patient metabolizes drugs, potentially offering safer and more effective pain relief. By targeting individual genetic variations, this approach aims to optimize pain management and minimize side effects.

What evidence suggests that this trial's treatments could be effective for post-surgical pain?

Research has shown that hydromorphone, which participants in this trial may receive as part of the pharmacogenomics (PGx) guided treatment arm, effectively manages post-surgical pain. One study found that it did not increase pain or the need for additional painkillers after surgery. Another study demonstrated that it helps relieve pain immediately after surgery and can also reduce depression and sleep problems. Hydromorphone is known to work better than some other pain medications for children after surgery. It has been used to treat various types of pain, including pain from surgery, injuries, and burns. Overall, hydromorphone has a strong track record for alleviating post-surgical pain. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for opioid-naive patients who need pain management after surgery. Participants must not have prior dependence on opioids or a history of substance abuse. They should be willing to take hydromorphone if their genetics show they metabolize drugs differently.

Inclusion Criteria

Able to read and understand study procedures

Willing to participate and sign an ICF

I haven't taken opioids in the 90 days before my surgery.

Exclusion Criteria

I understand the study procedures.

I can make decisions about my health care.

I have not had surgery in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive personalized opiate therapy based on pharmacogenetics, including hydromorphone for those with specific CYP2D6 metabolic activity

7 days

Daily monitoring during hospital stay

Follow-up

Participants complete a 7-day pain diary post-discharge and receive follow-up phone calls once per month for 90 days

90 days

3 follow-up phone calls

What Are the Treatments Tested in This Trial?

Interventions

• Hydromorphone

Trial Overview The study tests personalized pain management based on genetic testing (PGx). It aims to see if this approach can reduce long-term opioid dependency, improve pain control, and minimize side effects compared to standard oxycodone treatment.

How Is the Trial Designed?

Group I: Pharmacogenomics (PGx) guided treatment (hydromorphone) Experimental Treatment 2 Interventions

Patients who are poor CYP2D6 metabolizers or rapid CYP2D6 metabolizers with moderate or severe pain, will be prescribed either oral hydromorphone 2mg every 4 hours as needed or oral hydromorphone 4mg every 4 hours as needed, respectively.

Group II: Standard post-operative pain management (control) Active Control 2 Interventions

Patients in the control groups will follow the current hospital standard of care and receive oxycodone 5mg every 4 hours as needed for moderate pain and oxycodone 10mg every four hours as needed for severe pain.

Hydromorphone is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Dilaudid for:

• Moderate to severe pain

Approved in Canada as Hydromorphone for:

• Moderate to severe pain

Approved in European Union as Hydromorphone for:

• Moderate to severe pain

Who Is Running the Clinical Trial?

University of Tennessee Graduate School of Medicine

Lead Sponsor

Trials

17

Recruited

1,400+

Published Research Related to This Trial

In a multicenter, double-blind, placebo-controlled study involving opioid-tolerant patients with chronic low back pain, once-daily OROS hydromorphone ER significantly reduced pain intensity compared to placebo, with a median change in pain score of 0.2 units versus 1.6 units (p < 0.001).

Hydromorphone ER was well-tolerated, with 60.6% of patients experiencing at least a 30% reduction in pain scores, although 13% discontinued due to adverse events, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily OROS hydromorphone ER compared with placebo in opioid-tolerant patients with chronic low back pain. Hale, M., Khan, A., Kutch, M., et al.[2022]

In a study of 1,846 patients undergoing abdominal surgery, no significant relationship was found between the dose of intrathecal hydromorphone and the level of postoperative analgesia, suggesting that higher doses do not necessarily lead to better pain relief.

However, patients receiving high doses of hydromorphone (200-300 µg) experienced a higher rate of severe opioid-related adverse events in the postanesthesia care unit, indicating a potential safety concern with increased dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Review of Intrathecal Hydromorphone Dose Range and Complications. Charnin, JE., Weingarten, TN., Schroeder, DR., et al.[2023]

Hydromorphone is an effective semi-synthetic opioid for managing acute and chronic pain, with various administration routes studied, but it produces inactive metabolites that can lead to toxicity and neuroexcitatory effects.

Current evidence suggests that hydromorphone does not have a higher potential for abuse compared to other opioids, although further research is needed to clarify its safety profile, especially regarding toxicity and its use in nonmalignant pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydromorphone. Murray, A., Hagen, NA.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0007091223001277

Intraoperative hydromorphone decreases postoperative pain This study found that hydromorphone, an intermediate-acting opioid, did not lead to increased pain or opioid requirements postoperatively.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3747287/

Postoperative Pain Control - PMC - PubMed Central - NIH A recent observational study showed that single-dose intrathecal opioid followed by IV PCA resulted in better pain control than CEA in patients undergoing ...

3. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1567328/full

Efficacy and safety of hydromorphone for postoperative ... Hydromorphone-based PCIA enhances early postoperative pain relief in orthopedic surgery patients, alleviates postoperative depression and sleep disturbances.

4. bmcanesthesiol.biomedcentral.com bmcanesthesiol.biomedcentral.com/articles/10.1186/s12871-021-01412-8

Effectiveness of analgesia with hydromorphone hydrochloride ... Hydromorphone hydrochloride is a more effective analgesic than sufentanil for postoperative pain in pediatric patients following surgical repair ...

5. jpsmjournal.com jpsmjournal.com/article/S0885-3924(05)00033-3/fulltext

Hydromorphone Hydromorphone's analgesic properties have been studied in postoperative pain, acute trauma pain, burn wound pain, biliary and ureteral colic, and oral mucositis ...

6. journals.lww.com journals.lww.com/anesthesia-analgesia/fulltext/2016/09002/abstract_pr231__efficacy_and_safety_of.224.aspx

Abstract PR231: Efficacy and Safety of Hydromorphone for. ... The aim of this study was to evaluate the efficacy and safety of morphine and hydromorphone intravenous injection for postoperative analgesia in children.