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

Trial Summary

What is the purpose of this trial?

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 after robotic-assisted partial nephrectomy.

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.

What data supports the effectiveness of the drug combination for post-kidney surgery pain management?

Research shows that ibuprofen and paracetamol are effective for postoperative pain relief, with ibuprofen having a lower number needed to treat (NNT) of 2.7 compared to paracetamol's NNT of 4.6. Combining paracetamol with NSAIDs like ketoprofen can enhance pain relief, as seen in studies where these combinations reduced the need for stronger painkillers like morphine. ^{1 2 3 4 5}

Is ketorolac safe for managing post-surgery pain?

Ketorolac, a nonsteroidal anti-inflammatory drug, can cause temporary kidney problems and high potassium levels in some patients, especially those with existing kidney issues. These side effects improved after stopping the drug. ^{2 6 7 8 9}

How do NSAIDs differ from other drugs for post-kidney surgery pain management?

NSAIDs (nonsteroidal anti-inflammatory drugs) like ibuprofen and ketoprofen are unique because they provide pain relief without the use of opioids, which can have more severe side effects. They work by reducing inflammation and are often used as a first-line therapy after surgery, offering a safer alternative with fewer side effects compared to opioid medications. ^{10 11 12 13 14}

Research Team

Mark L Gonzalgo, MD, PhD

Principal Investigator

University of Miami

Eligibility Criteria

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

I am between 18 and 99 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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 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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. [2022]

2. France pubmed.ncbi.nlm.nih.gov

[Physico-chemical stability and sterility of non-opioid analgesics in solution]. [2016]

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Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study. [2019]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Systemic multimodality postoperative analgesia in vascular surgery]. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Propacetamol and ketoprofen after thyroidectomy. [2019]

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

Ketorolac-induced acute renal failure and hyperkalemia: report of three cases. [2019]

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

Renal failure and hyperkalemia associated with ketorolac tromethamine. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Acute treatment with dexketoprofen reduces penicillin induced epileptiform activity in wistar albino rats (dexketoprofen in penicillin induced seizure model). [2022]

9. New Zealand 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. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Nonopioid, Multimodal Analgesia as First-line Therapy After Otolaryngology Operations: Primer on Nonsteroidal Anti-inflammatory Drugs (NSAIDs). [2021]

11. Canada pubmed.ncbi.nlm.nih.gov

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

12. Russia (Federation) 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]. [2016]

13. England pubmed.ncbi.nlm.nih.gov

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

14. Cyprus pubmed.ncbi.nlm.nih.gov

Ketoprofen is superior to metamizole in relieving postoperative pain after head and neck tumor operation. [2015]