NSAIDs for Post-Kidney Surgery Pain Management

(No-PAIN Trial)

Overseen By Mark L Gonzalgo, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Must not be taking: Antiplatelets, Anticoagulants, Opioids

Disqualifiers: Allergy to NSAIDs, Heart disease, GI issues, 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: Unknown

Duration: 3 weeks

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in controlling pain without side effects after kidney surgery. It compares NSAIDs to standard pain medications such as acetaminophen and oxycodone. Individuals who have undergone robotic-assisted partial kidney surgery and have no history of heart issues or stomach problems may qualify. The trial aims to improve pain management for those recovering from surgery. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to advancements in safer pain management.

Will I have to stop taking my current medications?

If you are taking anti-platelet or anti-coagulation medications like warfarin, aspirin, or clopidogrel, you will need to stop taking them to participate in this trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NSAIDs, such as ibuprofen and ketorolac, are generally safe for relieving post-surgery pain. They might cause minor, temporary kidney issues in individuals with normal kidney function. One study found that NSAIDs do not increase the risk of heart problems, stomach bleeding, or additional bleeding during surgery. However, another study showed that aspirin could cause more serious kidney problems compared to ibuprofen.

Overall, NSAIDs are well-tolerated for short-term use, especially for managing post-surgery pain. While it's important to be aware of potential side effects, most people use these drugs without major issues. Consulting healthcare providers is essential to determine the best option for individual needs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the use of NSAIDs for managing post-kidney surgery pain because these medications, like ibuprofen and ketorolac, target inflammation directly, which is a key part of the pain experienced after surgery. Unlike opioids such as oxycodone and hydromorphone, which act on the brain to reduce pain perception and can have significant side effects and addiction potential, NSAIDs work by reducing the production of prostaglandins, substances that promote inflammation and pain. This could potentially offer a safer, non-addictive alternative for pain management, reducing reliance on opioids and their associated risks. Additionally, acetaminophen, often used in standard care, primarily reduces fever and minor aches but doesn't address inflammation directly.

What evidence suggests that NSAIDs are effective for post-kidney surgery pain management?

This trial will compare NSAIDs with standard care for managing pain after kidney surgery. Studies have shown that NSAIDs, a type of pain reliever, effectively control post-surgical pain by reducing swelling. Research suggests that NSAIDs might also protect the kidneys by lowering harmful swelling and stress in the body. Although there might be small, temporary effects on kidney function, these are usually not a concern for individuals with healthy kidneys. Overall, NSAIDs offer a promising option for managing pain after kidney surgery without heavily relying on stronger painkillers like opioids. ^{1 3 6 7 8}

Who Is on the Research Team?

Mark L Gonzalgo, MD, PhD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for adults aged 18-99 undergoing a specific minimally invasive surgery (robotic-assisted laparoscopic partial nephrectomy) for kidney tumors at select locations. Participants must understand and consent to the study's procedures. Excluded are pregnant individuals, those with allergies to NSAIDs, recent heart issues, history of GI complications or bleeding disorders, poor kidney function, or current/recent use of certain blood thinners and opioids.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

I am having a specific kidney surgery without complications at a University of Miami Hospital site.

Exclusion Criteria

I am currently taking blood thinners like warfarin or aspirin.

You are allergic to NSAIDs (pain-relief medications like aspirin or ibuprofen).

I have a history of stomach ulcers, GI bleeding, or a bleeding disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either NSAIDs or standard care treatment for pain management after robotic-assisted partial nephrectomy

3 weeks

In-hospital stay and follow-up visits

Follow-up

Participants are monitored for opioid use, pain scores, and adverse events post-surgery

Up to 20 days

Post-operative follow-up visit

What Are the Treatments Tested in This Trial?

Interventions

• Acetaminophen
• Hydromorphone
• Ibuprofen
• Ketorolac
• Oxycodone

Trial Overview The study aims to evaluate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs), such as Ketorolac and Ibuprofen, in managing post-surgery pain compared to other pain relievers like Acetaminophen, Oxycodone, and Hydromorphone after robotic-assisted surgery on renal masses.

How Is the Trial Designed?

Group I: Group 1: NSAID Experimental Treatment 5 Interventions

Participants in this group will be prescribed NSAIDs instead of the standard of care treatment. Participants will be in this group for approximately 21 days.

Group II: Group 2: No-NSAID Active Control 3 Interventions

Participants in this group will follow standard of care treatment. Participants will be in this group for approximately 21 days.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Published Research Related to This Trial

In a study of 60 patients undergoing major head and neck surgery, both ketoprofen and metamizole provided similar pain relief during the first 48 hours post-surgery.

However, ketoprofen was found to be more effective than metamizole in reducing pain on the 3rd postoperative day, indicating its potential for better long-term analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketoprofen is superior to metamizole in relieving postoperative pain after head and neck tumor operation. Jovic, R., Dragicevic, D., Komazec, Z., et al.[2015]

NSAIDs are generally more effective than paracetamol for pain relief in dental surgery, while their effectiveness is similar in major and orthopedic surgeries, indicating that the choice of pain management may depend on the type of surgery.

Paracetamol is a safer alternative to NSAIDs due to its lower incidence of adverse effects, making it a preferred option for high-risk patients; combining paracetamol with NSAIDs may enhance pain relief, but more research is needed to assess potential side effects from this combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. Hyllested, M., Jones, S., Pedersen, JL., et al.[2022]

In a study involving 237 patients, combining paracetamol, nefopam, and ketoprofen (PNK) significantly reduced morphine consumption and improved pain relief compared to morphine alone or other combinations, particularly in the first 24 hours after surgery.

The combination of these three non-opioid analgesics did not increase the incidence of morphine-related side effects, suggesting a safer approach to postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study. Beloeil, H., Albaladejo, P., Sion, A., et al.[2019]

In a study of 53 patients who underwent surgeries on the aorta and lower extremities, various combinations of non-narcotic analgesics were evaluated for effective postoperative pain relief, showing that multimodal regimens can provide good analgesia without narcotics.

The combination of paracetamol with tramadol not only led to a quicker onset of pain relief but also reduced the need for tramadol, making it a safer option for patients at high risk for complications from non-steroidal anti-inflammatory drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Systemic multimodality postoperative analgesia in vascular surgery]. Kazennov, VV., Shishkin, MN., Amerov, DB.[2019]

In a study involving 425 patients with postherniorrhaphy pain, 400 mg of ibuprofen was found to be more effective than a placebo and as effective as a compound analgesic containing acetylsalicylic acid, caffeine, and codeine.

The side effects of ibuprofen and the other medications tested were negligible, suggesting that ibuprofen is a safe and suitable alternative for managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relief of postoperative pain by ibuprofen: a report of two studies. Iles, JD.[2020]

In a study of 83 adult patients undergoing head and neck cancer surgery, a multimodal analgesia approach using tenoxycam and nefopam effectively managed postoperative pain, with only 8.4% experiencing adverse reactions.

The method proved to be simple and efficient, as it allowed for tailored pain management based on the severity of pain, with additional analgesics provided as needed for those with higher pain scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Postoperative analgesia with nefopam and non-steroidal anti-inflammatory drugs in patients after surgery for tumors of head and neck]. Balandin, VV., Gorobets, ES.[2016]

In a study involving 252 patients with postoperative pain from hip or knee replacement surgery, dexketoprofen trometamol and racemic ketoprofen demonstrated equivalent analgesic efficacy, indicating both are effective options for pain management.

Dexketoprofen trometamol showed a trend towards better tolerability, with fewer treatment-related adverse events (16%) compared to ketoprofen (21.3%), suggesting it may be a safer choice for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy and safety of intravenously administered dexketoprofen trometamol and ketoprofen in the management of pain after orthopaedic surgery: A multicentre, double-blind, randomised, parallel-group clinical trial. Zippel, H., Wagenitz, A.[2022]

In a study of 60 patients undergoing nasal surgery, intravenous ketoprofen provided significantly better postoperative pain relief and lower headache scores compared to pethidine, with lower pain scores observed at multiple time points post-surgery.

Patients receiving ketoprofen also experienced a faster recovery from anesthesia and required less additional pain medication, indicating its potential advantages in postoperative care without increasing nausea or vomiting risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of intravenous ketoprofen with pethidine for postoperative pain relief following nasal surgery. Elhakim, M.[2022]

Ketorolac tromethamine is an effective nonsteroidal anti-inflammatory drug (NSAID) used for pain management, particularly in emergency and postoperative settings, but it can lead to acute renal failure and hyperkalemia in susceptible individuals.

In three reported cases, patients with risk factors for kidney issues developed these complications after receiving moderate doses of ketorolac, but both conditions were reversible upon stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac-induced acute renal failure and hyperkalemia: report of three cases. Haragsim, L., Dalal, R., Bagga, H., et al.[2019]

Dexketoprofen trometamol demonstrated a significant reduction in epileptiform activity in a rat model of seizures, particularly at doses of 25 mg/kg and 50 mg/kg, indicating its potential as an anti-seizure agent.

The study involved 28 male Wistar rats and used electrocorticography to measure the effects of dexketoprofen on seizure activity induced by penicillin, showing that even a low dose (5 mg/kg) had some efficacy in reducing spike frequency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute treatment with dexketoprofen reduces penicillin induced epileptiform activity in wistar albino rats (dexketoprofen in penicillin induced seizure model). Demirsoy, MS., Erdil, A., Çolak, S., et al.[2022]

In a study of 97 patients undergoing thyroid surgery, ketoprofen provided significantly better pain relief compared to propacetamol alone in the first two hours post-surgery, indicating its greater efficacy as an analgesic.

The combination of propacetamol and ketoprofen did not enhance pain relief compared to ketoprofen alone, suggesting that using both together may not be necessary for effective postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propacetamol and ketoprofen after thyroidectomy. Fourcade, O., Sanchez, P., Kern, D., et al.[2019]

In a case study of three patients treated with ketorolac tromethamine, two developed acute renal failure or hyperkalemia, highlighting the potential renal risks associated with this nonsteroidal anti-inflammatory drug (NSAID).

The complications were reversible in two patients after stopping the medication, emphasizing the importance of monitoring renal function in patients at risk when using ketorolac, as it can affect prostaglandin synthesis and renal vasodilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal failure and hyperkalemia associated with ketorolac tromethamine. Pearce, CJ., Gonzalez, FM., Wallin, JD.[2022]

NSAIDs, especially when combined with acetaminophen, are highly effective for managing postoperative pain and are safer than opioid-based regimens, as shown by a comprehensive review of various guidelines and studies.

The review emphasizes that misconceptions about NSAIDs being less potent and having high bleeding risks are unfounded, and it recommends using multimodal analgesia as the first-line therapy after surgery, reserving opioids for severe pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonopioid, Multimodal Analgesia as First-line Therapy After Otolaryngology Operations: Primer on Nonsteroidal Anti-inflammatory Drugs (NSAIDs). Cramer, JD., Barnett, ML., Anne, S., et al.[2021]

The study confirmed that mixtures of non-opioid analgesics (paracetamol with ketoprofen, paracetamol with nefopam, and ketoprofen with nefopam) remain chemically stable and sterile for at least 24 hours.

These findings support the safe use of these analgesic combinations in a single ready-to-use solution for effective postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physico-chemical stability and sterility of non-opioid analgesics in solution]. Troïtzky, A., Tirault, M., Lefeuvre, S., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6516878/

NSAIDs on Postoperative Renal Function in Adults NSAIDs used for pain relief after surgery may have only small, temporary negative effects on kidney function in adults with normal renal function.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2352556825001134

NSAID Use & Acute Kidney Injury in Nephrectomies In contrast, NSAIDs may exert a protective effect on the kidneys by reducing the release of proinflammatory factors and alleviating renal ischemia‒reperfusion ...

3. withpower.com withpower.com/trial/phase-2-kidney-neoplasms-6-2023-83d25

NSAIDs for Post-Kidney Surgery Pain Management The purpose of this study is to see how effective non-steroidal anti-inflammatory drugs (NSAIDs) are at controlling pain without side effects in participants ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03584373?tab=results

Pain Outcomes of Non-opioid vs. Opioid Analgesia for ... Ketorolac will be administered post surgery to compare pain outcomes to that of Percocet. Acetaminophen: Acetaminophen is an over-the counter pain medication ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3488408/

Pain Management in Laparoscopic Donor Nephrectomy NSAIDS are found to have little effect on surgical stress response and organ dysfunction [30, 31]. But on the other hand, it has been shown that NSAIDS provide ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7563114/

Comparison of Postoperative Renal Function between Non ... This study compared postoperative renal function and postoperative outcomes between patients using NSAID and patients using opioids for PCA in nephrectomy.

7. scientificarchives.com scientificarchives.com/article/nsaid-associated-renal-injury-mechanisms-risks-and-safer-strategies

NSAID-associated Renal Injury: Mechanisms, Risks, and ... Aspirin had the highest mortality rate (18.7%), while ibuprofen had the lowest (3.8%). The median onset for renal injury was 6 days, with 79.3% of events ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053077025008134

Nonsteroidal Anti-Inflammatory Drugs as Part of a ... This meta-analysis evaluates the efficacy and safety of NSAIDs as a multimodal pain management tool following cardiac surgery. Methods. An ...