Pain Medication for Postoperative Pain

(CARES Trial)

Recruiting at 8 trial locations

Overseen By Sarah Clark, BA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Michigan

Must not be taking: Opioids, NSAIDs

Disqualifiers: Other surgery, Life expectancy, 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: 7 days

900 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two common pain relief methods for surgeries such as gallbladder removal, hernia repair, or breast lump removal. It aims to determine which is more effective: NSAIDs (a type of pain reliever) plus acetaminophen, or low-dose opioids plus acetaminophen. Researchers believe the NSAID option might be more effective and cause fewer side effects. Individuals who have not used pain medications extensively before surgery and are planning one of these specific surgeries might be suitable for the trial. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, allowing researchers to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you have not used significant pain medications like opioids or NSAIDs recently. If you've used these medications frequently in the past 30 days, you may not be eligible to participate.

What is the safety track record for these treatments?

Research shows that both NSAIDs and opioids have been studied for post-surgery pain relief. NSAIDs, such as ibuprofen and meloxicam, are generally safe for managing short-term pain when used correctly. Studies indicate that NSAIDs have minor side effects similar to other pain medications, without significantly increasing wound problems.

In contrast, opioids often cause more noticeable side effects, including dizziness, drowsiness, nausea, and vomiting. One study found that some opioids, like tramadol, had higher rates of serious side effects compared to others, such as oxycodone and hydrocodone.

In summary, both treatments have been used safely in patients, but NSAIDs typically cause fewer side effects than opioids. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for postoperative pain because they explore different approaches to pain management. The NSAID regimen offers a non-opioid alternative, which could reduce the risk of dependency and side effects associated with opioids. The opioid regimen is being examined to potentially optimize dosing and minimize adverse effects. By comparing these two regimens, researchers hope to find effective pain relief options that improve patient recovery while minimizing risks.

What evidence suggests that this trial's treatments could be effective for postoperative pain?

In this trial, participants will be assigned to different treatment arms to manage postoperative pain. Research has shown that combining NSAIDs (a type of pain reliever) with acetaminophen often manages pain after surgery better than opioids. Participants in the NSAID regimen arm may experience effective pain relief with fewer side effects. Studies have found that NSAIDs can relieve pain more effectively and with fewer side effects. For instance, a review found that NSAIDs worked better than weaker opioids for post-surgery pain. Meanwhile, participants in the opioid regimen arm may find opioids effective, but there is concern about long-term use. Additionally, some opioids may not reduce pain as well as NSAIDs after surgery. Overall, NSAIDs appear to be a safer and more effective choice for many patients. ^{1 2 3 5 6}

Who Is on the Research Team?

Mark Bicket, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

The CARES trial is for patients having low-risk surgeries like gallbladder removal, hernia repair, or breast lump removal. They must not have used significant pain medication recently and should be free from other surgeries or life-threatening conditions in the next 6 months. Those with specific allergies to NSAIDs, opioids, or acetaminophen can't join.

Inclusion Criteria

I haven't used strong painkillers or NSAIDs much before surgery.

I am having a low-risk surgery like gallbladder removal, hernia repair, or breast lumpectomy.

Exclusion Criteria

I do not expect to have any surgeries in the next 6 months and believe I will live longer than 6 months.

I am not allergic or unable to take NSAIDs, opioids, or acetaminophen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either NSAIDs plus acetaminophen or low dose opioids plus acetaminophen for pain management post-surgery

7 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of pain intensity and adverse events

6 months

Multiple visits (in-person and virtual)

Long-term follow-up

Participants are monitored for chronic pain and healthcare utilization related to pain

180 days post surgery

What Are the Treatments Tested in This Trial?

Interventions

• Acetaminophen
• NSAID
• Opioid

Trial Overview

This study compares two pain management strategies after surgery: one group will receive NSAIDs plus acetaminophen while the other gets low-dose opioids plus acetaminophen. Patients are randomly assigned to these groups to see which has better outcomes and fewer side effects.

How Is the Trial Designed?

Group I: Opioid regimen Experimental Treatment 2 Interventions

Group II: NSAID regimen Experimental Treatment 2 Interventions

Surgical teams will elect for one of the medications within the treatment arm to which the patient is randomized.

NSAID is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as NSAIDs for:

• Pain relief
• Inflammation
• Fever reduction
• Postoperative pain management

Approved in United States as NSAIDs for:

• Pain relief
• Inflammation
• Fever reduction
• Postoperative pain management
• Arthritis
• Menstrual cramps

Approved in Canada as NSAIDs for:

• Pain relief
• Inflammation
• Fever reduction
• Postoperative pain management

Approved in Japan as NSAIDs for:

• Pain relief
• Inflammation
• Fever reduction

Approved in China as NSAIDs for:

• Pain relief
• Inflammation
• Fever reduction

Approved in Switzerland as NSAIDs for:

• Pain relief
• Inflammation
• Fever reduction
• Postoperative pain management

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Published Research Related to This Trial

Low doses of ketoprofen (0.5-5 mg/kg) effectively reduced guarding behavior in rats after surgical incision, indicating its potential as a targeted analgesic for postoperative pain.

Both locally applied sustained-release microparticles and intrathecal ketoprofen showed similar effects, specifically inhibiting guarding without affecting responses to heat or mechanical stimuli, suggesting a modality-specific action of ketoprofen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketoprofen produces modality-specific inhibition of pain behaviors in rats after plantar incision. Spofford, CM., Ashmawi, H., Subieta, A., et al.[2022]

New analgesic medications and techniques, including preoperative nonsteroidal anti-inflammatory drugs and intraoperative neuraxial analgesia, can improve the management of acute postoperative pain, reducing risks associated with both undertreatment and overtreatment.

These innovative approaches may offer enhanced safety and efficacy compared to traditional pain management methods, such as postoperative oral analgesics, potentially leading to better patient outcomes and shorter hospital stays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent management advances in acute postoperative pain. Argoff, CE.[2022]

Short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) for managing acute postoperative pain does not significantly increase the risk of serious adverse effects such as renal dysfunction, bleeding, or gastric complications when used appropriately.

Given the ongoing opioid epidemic, NSAIDs present a safer alternative for postoperative pain management, highlighting the need to consider them as viable options in pain control strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are NSAIDs Safe? Assessing the Risk-Benefit Profile of Nonsteroidal Anti-inflammatory Drug Use in Postoperative Pain Management. Chang, RW., Tompkins, DM., Cohn, SM.[2021]

A systematic review of 13 studies involving 920 children found that the efficacy and safety of ketorolac for postoperative pain management remain uncertain due to very low-quality evidence and significant variability in study designs.

While some studies reported a reduction in pain intensity with ketorolac compared to placebo, the overall data were insufficient to draw definitive conclusions about its effectiveness or safety, particularly regarding adverse events like bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac for postoperative pain in children. McNicol, ED., Rowe, E., Cooper, TE.[2022]

Non-opioid analgesics like paracetamol, NSAIDs, and gabapentinoids significantly reduce post-operative morphine requirements, with gabapentinoids showing the highest reduction of ≥13 mg morphine per 24 hours when used alone.

The evidence for the effectiveness of glucocorticoids in reducing opioid use is less convincing, and there is a need for more research on the benefits of combination regimens of these non-opioid drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. Dahl, JB., Nielsen, RV., Wetterslev, J., et al.[2022]

A single dose of systemic ketorolac (60 mg) significantly reduces early postoperative pain and opioid consumption, making it an effective adjunct for pain management in surgical patients, based on a systematic review of 13 trials involving 782 subjects.

The 60 mg dose of ketorolac also decreases the incidence of postoperative nausea and vomiting, enhancing its safety profile compared to lower doses, which did not show significant benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials. De Oliveira, GS., Agarwal, D., Benzon, HT.[2022]

A single study involving 201 participants indicated that intravenous (IV) ibuprofen provided at least 50% pain relief in 32% of patients compared to 22% in the placebo group, suggesting a potential benefit, although the evidence is of very low certainty.

The study found no serious adverse events associated with IV ibuprofen, and the rate of any adverse events was similar between ibuprofen and placebo, indicating that it may be a safe option for postoperative pain management, but further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose intravenous ibuprofen for acute postoperative pain in adults. Ferguson, MC., Schumann, R., Gallagher, S., et al.[2023]

Postoperative therapy with NSAIDs after tonsillectomy may lead to a higher rate of reoperations, suggesting that their use should be approached with caution.

COX-2 inhibitors combined with intravenous opioids enhance recovery and functional outcomes after knee replacement surgery, indicating a beneficial approach for pain management in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New insights in postoperative pain therapy]. Brack, A., Böttiger, BW., Schäfer, M.[2006]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective for managing acute postoperative pain and can enhance pain relief when combined with opioids and local anesthetics, leading to reduced narcotic use and improved overall analgesia.

Combining NSAIDs with opioids not only improves pain management but also offers benefits like better respiratory function and reduced nausea, suggesting that NSAIDs may contribute to faster and higher-quality recovery after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of nonsteroidal anti-inflammatory drugs in the management of postoperative pain. Moote, C.[2022]

Postoperative pain is common and can lead to chronic pain if not treated effectively; multimodal analgesia, including NSAIDs and opioids, is recommended to manage this pain safely.

The combination of dexketoprofen and tramadol is highlighted as a particularly effective and safe option for postoperative pain control, helping to minimize opioid use and reduce the risk of persistent pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Insights Into the Pharmacological Management of Postoperative Pain: A Narrative Review. Mayoral Rojals, V., Charaja, M., De Leon Casasola, O., et al.[2022]

In a study involving 157 patients undergoing shoulder surgery, those who received celecoxib experienced a significant reduction in opioid use, taking fewer morphine-equivalent doses (MEDs) at both 3 weeks (-168 MEDs) and 6 weeks (-199 MEDs) post-surgery compared to those on placebo.

Celecoxib was particularly effective in reducing opioid consumption in patients undergoing total shoulder replacement, while no significant difference was observed in those undergoing rotator cuff repair, highlighting the importance of multimodal pain management strategies in orthopedic surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celecoxib significantly reduces opioid use after shoulder arthroplasty. Burns, KA., Robbins, LM., LeMarr, AR., et al.[2021]

Ketorolac can significantly reduce the required dose of opioids by an average of 36% in postoperative patients, improving pain management when used alongside opioids.

While ketorolac enhances analgesia, it does not significantly decrease opioid-related side effects, and its use should be cautious, especially in vulnerable populations, due to increased risks of adverse events with higher doses or prolonged use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac in the era of cyclo-oxygenase-2 selective nonsteroidal anti-inflammatory drugs: a systematic review of efficacy, side effects, and regulatory issues. Macario, A., Lipman, AG.[2022]

A multimodal approach to pain control after orthopedic surgery, which includes nonopioid agents like intravenous acetaminophen and intranasal ketorolac, offers better pain relief with fewer side effects compared to using opioids alone.

This review highlights the importance of incorporating newer nonopioid medications alongside established treatments like ketamine and gabapentinoids to enhance analgesia, especially in the context of the ongoing opioid epidemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updates on Multimodal Analgesia for Orthopedic Surgery. Pitchon, DN., Dayan, AC., Schwenk, ES., et al.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11973795/

Comparing Analgesic Regimen Effectiveness and Safety ...

The primary effectiveness outcome is patient-reported worst daily pain intensity over the first 7 days after surgery. The primary safety outcome ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7592505/

Efficacy of non-opioid analgesics to control postoperative pain

Among abdominal procedures, MIV was associated with significantly greater pain reductions versus acetaminophen, ketorolac, other medications, and placebo (Fig.

3.

journals.lww.com

journals.lww.com/jaaosglobal/fulltext/2022/04000/meloxicam_versus_celecoxib_for_postoperative.2.aspx

Meloxicam versus Celecoxib for Postoperative Analgesia...

The incidence of wound complications did not significantly differ between the groups: 0.06%, 0.07%, and 0.22% in the celecoxib, meloxicam 15 mg/d, and meloxicam ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05695664

Postoperative Analgesic Effects of Ibuprofen Versus ...

NSAIDs also have several side effects, but a study has proven NSAIDs to be safe for controlling acute postoperative pain if they are used appropriately.6 ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0090825818311326

Celecoxib versus ketorolac following robotic hysterectomy ...

The primary outcome variable was postoperative pain measured on a visual analog scale at different time points. The secondary outcome variable was the amount of ...

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trialsjournal.biomedcentral.com

trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08326-z

Effect of non-steroidal anti-inflammatory drugs on the ... - Trials

The expected outcome of this study is an improvement in the management of acute postoperative pain in cardiac surgery with a multimodal strategy ...