No vs. Minimal Opioids After Inguinal Hernia Repair

Recruiting at 7 trial locations

Overseen By Noah Tocci, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Clayton Petro

Must not be taking: Opioids, NSAIDs

Disqualifiers: Chronic pain, Extensive surgery, 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

Compensation: Varies

Number of Visits: 1

Duration: Immediate post-operative period

904 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether avoiding opioids for pain after hernia repair is as effective as using a small amount. Researchers aim to determine if patients who forgo opioids experience similar pain control and quality of life after surgery as those who take a few opioid pills. Individuals who have had or plan to have a simple inguinal hernia repair and can tolerate general anesthesia may find this trial suitable. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, with the goal of understanding its benefits for more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on opioids for chronic pain management, you cannot participate.

What is the safety track record for these treatments?

Research has shown that taking a small amount of opioids, such as a few Oxycodone tablets, after inguinal hernia surgery is common and generally safe. In past studies, patients who took a small amount of opioids did not experience more pain than those who abstained. These studies suggest that small amounts of opioids are usually well-tolerated.

Since this trial is in the later stages, the safety of using minimal opioids has been thoroughly researched. Earlier studies have typically addressed any major safety issues. Overall, using a small amount of opioids after surgery appears to be a safe way to manage pain for most patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the trial exploring minimal vs. no opioids after inguinal hernia repair because it could reshape pain management for this common procedure. Unlike the standard approach, which often relies on higher doses of opioids, this trial investigates the effectiveness of significantly reducing or entirely eliminating opioid use. This is critical because it could minimize the risk of opioid dependency and side effects, presenting a safer alternative for patients. By potentially demonstrating that minimal or no opioids can effectively manage post-surgical pain, this approach could lead to a shift in post-operative care practices, prioritizing patient safety and well-being.

What evidence suggests that this trial's treatments could be effective for inguinal hernia repair?

This trial will compare minimal opioid use to no opioids after inguinal hernia surgery. Studies have shown that using very few opioids can be as effective as not using any. Research indicates that pain relief was similar whether patients used a small amount of opioids or none. For example, patients who took limited opioids after surgery had similar recovery experiences to those who took none. This suggests that fewer opioids might not negatively affect pain relief or recovery. The goal is to manage pain effectively while reducing opioid use, which can lead to side effects and dependence. ^{1 2 4 6 7}

Who Is on the Research Team?

Clayton C Petro, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are having elective inguinal hernia repairs and can handle general anesthesia. It's not suitable for those with conditions that might complicate surgery or recovery.

Inclusion Criteria

I can safely undergo general anesthesia.

I am scheduled for surgery to repair one or both sides of my groin hernia.

Exclusion Criteria

Patients who are not able to understand and sign a written consent form

I cannot undergo surgery with general anesthesia.

I cannot tolerate opioids or NSAIDs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo inguinal hernia repair and are randomized to receive either minimal opioids or no opioids post-operatively

Immediate post-operative period

Follow-up

Participants are monitored for safety, opioid refill requests, and quality of life at 30 days post-operatively

4 weeks

1 visit (in-person) at one month

What Are the Treatments Tested in This Trial?

Interventions

• Minimal opioids
• No opioids

Trial Overview The study is testing if avoiding opioids after hernia surgery is just as good as giving a small amount (5 tablets of Oxycodone, or another drug if there's an intolerance). They're looking at the need for more pain meds and quality of life after a month.

How Is the Trial Designed?

Group I: No opioids Experimental Treatment 1 Intervention

Standard of care

Group II: Minimal Opioids Experimental Treatment 1 Intervention

Standard of care 5 tablets of Oxycodone (5mg) every 6 hours as needed for pain

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

Approved in United States as Oxycodone for:

• Severe pain requiring opioid treatment
• Acute postoperative pain

Approved in European Union as Oxycodone for:

• Severe pain requiring opioid treatment
• Acute postoperative pain

Approved in Canada as Oxycodone for:

• Severe pain requiring opioid treatment
• Acute postoperative pain

Who Is Running the Clinical Trial?

Clayton Petro

Lead Sponsor

Trials

5

Recruited

1,600+

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

In a study of 522 patients recovering from bunionectomy surgery, the dual-opioid Q8003 (morphine/oxycodone combination) showed significantly greater pain relief compared to either morphine or oxycodone alone, with higher pain intensity difference scores over 24 and 48 hours.

While Q8003 had a higher total morphine equivalent dose, it resulted in fewer patients needing additional ibuprofen for pain relief and only a modest increase in adverse events, indicating it is an effective option for managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3, randomized, double-blind comparison of analgesic efficacy and tolerability of Q8003 vs oxycodone or morphine for moderate-to-severe postoperative pain following bunionectomy surgery. Richards, P., Riff, D., Kelen, R., et al.[2022]

In a study of 66 cancer patients using Xtampza ER™, an oxycodone extended-release capsule, there was a statistically significant reduction in pain scores after starting the medication, with mean reductions of -0.7 and -1.1 at follow-up visits.

Despite the reduction in pain scores, the changes were clinically insignificant (less than the 2-point threshold), and over half of the patients discontinued OERC by the second follow-up, indicating a need for further research on its long-term efficacy and safety in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxycodone Extended-Release Capsule Utilization for Pain Management in a Cancer Palliative Care Clinic: A Retrospective Review. Fortunato, J., Kullgren, J., Houchard, G., et al.[2023]

MoxDuo, a combination of immediate-release morphine and oxycodone, showed significantly better pain relief compared to its individual components in patients with moderate to severe postoperative pain, particularly in the 12 mg/8 mg dosage group.

The MoxDuo 6 mg/4 mg dosage resulted in a 50-75% reduction in common opioid-related side effects like nausea and dizziness compared to equivalent doses of morphine and oxycodone, suggesting it may be a safer option for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic and adverse effects of a fixed-ratio morphine-oxycodone combination (MoxDuo) in the treatment of postoperative pain. Richards, P., Riff, D., Kelen, R., et al.[2019]

The discovery of the ORL1 receptor led to the identification of nociceptin, an endogenous ligand that can produce a range of effects including hyperalgesia, analgesia, and changes in behavior, indicating its complex role in pain modulation and other physiological processes.

Nociceptin is derived from the precursor protein prepronociceptin and has distinct effects depending on its form, with NocII enhancing locomotor activity and nocistatin acting as an antagonist to nociceptin's hyperalgesic effects, suggesting potential therapeutic targets for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cloning of prepronociceptin has led to the discovery of other biologically active peptides]. Costentin, J., Florin, S., Suaudeau, C., et al.[2023]

Opioid receptors, including mu (MOR), delta (DOR), and kappa (KOR), are crucial for mediating pain relief (analgesia) in animal models, while the role of the nociceptin receptor (ORL) remains unclear with mixed effects on pain.

A comparative analysis of opioid receptors across six vertebrate species suggests that these receptors evolved through gene duplication, with the MOR showing signs of rapid evolution, indicating potential differences in pain management across species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolution of vertebrate opioid receptors. Stevens, CW.[2023]

In a study involving 405 patients with moderate-to-severe postoperative pain after bunionectomy, both doses of oxycodone HCl/niacin tablets significantly reduced pain intensity compared to placebo, demonstrating their efficacy in pain management.

The treatment was generally well tolerated, with most adverse events being mild or moderate, and no serious adverse events reported, indicating a favorable safety profile for oxycodone HCl/niacin tablets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oxycodone HCl/niacin tablets for the treatment of moderate-to-severe postoperative pain following bunionectomy surgery. Daniels, SE., Spivey, RJ., Singla, S., et al.[2022]

Lofentanil, a mu-opioid receptor-selective agonist, was found to be a potent agonist for the nociceptin receptor (ORL1), indicating that some opioids can activate this receptor, which is distinct from traditional opioid receptors.

The study suggests that while some opioids can act on the nociceptin receptor, others may exhibit antagonistic or partial agonistic effects, highlighting the potential for developing new nonpeptide drugs that target the nociceptin receptor without affecting classical opioid receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid activity profiles indicate similarities between the nociceptin/orphanin FQ and opioid receptors. Hawkinson, JE., Acosta-Burruel, M., Espitia, SA.[2023]

The nociceptin/orphanin FQ system, involving the new OP(4) receptor, shows potential for drug development, as OP(4) agonists could help manage various conditions like neuropathic pain, anxiety, and drug dependence, while OP(4) antagonists may serve as general analgesics.

Unlike traditional opioids, nociceptin can produce spinal analgesia but may also counteract the effects of conventional opioids, highlighting the need for careful consideration of its unique effects in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nociceptin receptor as a potential target in drug design. Smith, PA., Moran, TD.[2003]

A study of 173 patients undergoing different types of inguinal hernia repairs (open, laparoscopic, and robotic) found no significant differences in opiate prescription amounts or pain management needs post-surgery.

The results suggest that the assumption that minimally-invasive hernia repair techniques lead to less postoperative pain may not be accurate, as all techniques required similar levels of pain medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sage wisdom or anecdotal dictum? Equivalent opioid use after open, laparoscopic, and robotic inguinal hernia repair. Sheldon, RR., Do, WS., Weiss, JB., et al.[2019]

Patients undergoing open inguinal hernia repair experienced similar postoperative pain levels and satisfaction with pain control compared to those who had minimally invasive surgery, despite the common belief that open surgery causes more pain.

A significant portion of patients (over one-third) did not require any opioids after discharge, suggesting that prescribing 0 to 8 tablets of 5 mg oxycodone may be sufficient for most opioid-naive patients undergoing this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid utilization in minimally invasive versus open inguinal hernia repair. Knight, AW., Habermann, EB., Ubl, DS., et al.[2020]

In a study of 79 patients undergoing thumb carpometacarpal arthroplasty or distal radius ORIF, the combination of oxycodone, acetaminophen, and ketorolac showed a trend towards better postoperative pain control and reduced opioid usage compared to other regimens.

Although not statistically significant, the group receiving oxycodone, acetaminophen, and ketorolac experienced fewer complications, suggesting that this combination may enhance safety and efficacy in managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-Modal Pain Control in Ambulatory Hand Surgery. Harrison, RK., DiMeo, T., Klinefelter, RD., et al.[2018]

The new oxycodone 10-mg/acetaminophen 325-mg formulation (Percocet) was found to be more effective than a higher dose of oxycodone alone in managing acute pain after oral surgery, based on a study of 141 patients.

This combination not only provided faster pain relief but also resulted in fewer treatment-related side effects, highlighting its potential as a safer alternative for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo-controlled comparison of the analgesic efficacy of oxycodone 10 mg/acetaminophen 325 mg versus controlled-release oxycodone 20 mg in postsurgical pain. Gammaitoni, AR., Galer, BS., Bulloch, S., et al.[2019]

Orphanin FQ (OFQ) is the only peptide from preproorphanin FQ (ppOFQ) that effectively binds to and activates the ORL1 receptor, as demonstrated by its ability to stimulate [35S]-GTPgammaS binding in adult rat brain.

The peptide OFQ II(1-28) does not bind to mu opioid receptors or ORL1 receptors, indicating that its analgesic effects are not mediated through these receptors, despite behavioral studies suggesting it has pain-relieving properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binding and GTPgammaS autoradiographic analysis of preproorphanin precursor peptide products at the ORL1 and opioid receptors. Neal, CR., Owens, CE., Taylor, LP., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31229314/

Opioid utilization in minimally invasive versus open ... Conclusion: Postdischarge opioid utilization was clinically similar between patients undergoing open and minimally invasive surgery inguinal ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05929937?term=delta%20opioid&viewType=Table&rank=2

No Opioids vs. Minimal Opioids Following Inguinal Hernia Repair Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0039606024008328

Open versus laparoscopic versus robotic inguinal hernia ... Open inguinal hernia repair was more commonly used in comorbid patients and recurrent hernias, but the techniques had comparable rates of wound complications.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2794301

Feasibility of Prospectively Comparing Opioid Analgesia ... More specifically, 12 patients (17%) had concerns about the efficacy of OFA and 8 patients (11%) did not want to take opioids after surgery. The ...

5. cureus.com cureus.com/articles/308181-comparing-the-postoperative-analgesic-efficacy-of-ketorolac-and-tramadol-after-open-inguinal-hernia-mesh-repair-a-randomized-controlled-trial

Comparing the Postoperative Analgesic Efficacy of ... In our study, we compared the analgesic efficacy of ketorolac with a weak opioid, tramadol, following open inguinal hernia repair. Pain ...

6. achqc.org achqc.org/data

Data Requests Evaluation of nerve management and outcomes in open inguinal hernia repair ... Minimal Opioids Following Inguinal Hernia Repair. 8/4/2023. Bryan Ellis, DO.

7. trialx.com trialx.com/clinical-trials/listings/250498/no-opioids-vs-minimal-opioids-following-inguinal-hernia-repair/?&geo_lat=33.7420005&geo_lng=-117.8236391&radius=10&place=Tustin&user_country=United%20States

No Opioids vs. Minimal Opioids Following Inguinal Hernia ... The investigators hypothesize that not prescribing opioids after uncomplicated, outpatient IHR will be non-inferior to prescribing opioids (5 ...