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

208 Participants Needed

Trial Summary

What is the purpose of this trial?

The main questions this study aims to answer are: Does perioperative PGx personalized opiate therapy reduce persistent post-operative opioid use dependency, improve pain management and reduce opiate related adverse events in opioid naïve patients after surgery? Participants will: Take hydromorphone if the PGx results determine they have a SNP indicating high or low metabolic activity in the CYP2D6 enzyme. Complete a 7-day pain diary post-discharge. Complete a follow-up phone call once per month for 90 days.

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 data supports the effectiveness of the drug Hydromorphone for post-surgical pain?

Research shows that hydromorphone is a potent pain reliever, about 3-5 times stronger than morphine and heroin, making it effective for managing post-surgical pain. It is well-accepted by patients and does not cause significant side effects, making it a suitable alternative to other opioids for post-surgical pain relief. ^{1 2 3 4 5}

Is hydromorphone safe for use in humans?

Hydromorphone has been studied for safety in various settings, including postoperative pain management and chronic pain. Common side effects are typical of strong painkillers but usually do not require special treatment. No serious heart or breathing problems were observed in the studies reviewed. ^{5 6 7 8 9}

How is the drug Hydromorphone used in personalized opiate therapy for post-surgical pain different from other treatments?

Hydromorphone in personalized opiate therapy is unique because it considers individual patient responses to opioids, which can vary widely, to tailor the treatment for optimal pain relief. This approach aims to improve patient care by potentially using genetic and biochemical data to predict how well a patient will respond to the drug, unlike standard treatments that often rely on trial and error. ^{2 4 10 11 12}

Eligibility Criteria

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

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

Able to read and understand study procedures

Willing to participate and sign an ICF

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pain management for joint arthroplasty: preemptive analgesia. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Retrospective Review of Intrathecal Hydromorphone Dose Range and Complications. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical analgesic assay of repeated and single doses of heroin and hydromorphone. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic modeling of hydromorphone in cardiac surgery patients during postoperative pain therapy. [2014]

5. Germany pubmed.ncbi.nlm.nih.gov

[Postoperative pain therapy with hydromorphone and metamizole. A prospective randomized study in intravenous patient-controlled analgesia (PCA)]. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Once-daily OROS hydromorphone ER compared with placebo in opioid-tolerant patients with chronic low back pain. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Hydromorphone. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

The side effects of morphine and hydromorphone patient-controlled analgesia. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Patient-Controlled Analgesia After Cardiac Surgery With Median Sternotomy: No Advantages of Hydromorphone When Compared to Morphine. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy of an Acute Pain Titration Protocol Driven by Patient Response to a Simple Query: Do You Want More Pain Medication? [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Variations in opioid responsiveness. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Novel polymeric bioerodable microparticles for prolonged-release intrathecal delivery of analgesic agents for relief of intractable cancer-related pain. [2018]