Ketorolac Injection for Kidney Stones

Recruiting at 1 trial location

Overseen By Karla Bergeron, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington University School of Medicine

Must not be taking: NSAIDs, Steroids, Anti-inflammatories

Disqualifiers: Gastrointestinal ulcers, Ureteral obstruction, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Ketorolac, an anti-inflammatory medication, to determine if it can reduce inflammation and ease discomfort for individuals receiving a stent during kidney stone treatment. Researchers aim to understand if Ketorolac can improve symptoms related to the stent. Participants will receive either a Ketorolac injection or a placebo (a harmless saline solution) before their procedure. The trial seeks individuals with kidney stones who plan to have a stent placed. As an Early Phase 1 trial, this research focuses on understanding how Ketorolac works in people, offering participants a chance to contribute to early-stage medical research.

Will I have to stop taking my current medications?

If you are taking chronic NSAIDs (non-steroidal anti-inflammatory drugs) or steroids, you will need to stop them to participate in this trial. However, taking a daily low-dose Aspirin (81 mg) is allowed.

Is there any evidence suggesting that Ketorolac is likely to be safe for humans?

Research has shown that ketorolac is generally safe when used for short periods and at normal doses. Studies have found that it does not significantly increase the risk of kidney failure in the short term. However, it can cause side effects such as nausea and stomach pain, especially when combined with strong painkillers like opioids. Notably, using ketorolac for more than five days can raise the risk of sudden kidney problems. This trial involves only a single dose, suggesting a lower risk of these issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using Ketorolac Trometamol for kidney stones because it offers a potential advantage over traditional pain management options like opioids and acetaminophen. Unlike these standard treatments, Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) that reduces inflammation and pain without the risk of addiction associated with opioids. Additionally, its one-time intravenous administration before a ureteroscopic procedure could provide rapid pain relief, which is crucial for patients dealing with the intense discomfort of kidney stones. This different mechanism and delivery method make Ketorolac a promising alternative for managing pain in kidney stone patients.

What evidence suggests that Ketorolac might be an effective treatment for kidney stones?

Research shows that ketorolac, a type of pain reliever, effectively reduces pain in people with kidney stones. In this trial, participants in the intervention group will receive a one-time intravenous injection of ketorolac before the ureteroscopic procedure. Studies indicate that ketorolac, administered through an IV or as a nasal spray, provides significant relief from kidney stone pain. This suggests ketorolac can help manage the discomfort associated with kidney stones. While the focus here is on inflammation and symptoms from stents, existing evidence strongly supports ketorolac's ability to relieve pain in kidney stone cases. ^{1 3 6 7 8}

Who Is on the Research Team?

Alana Desai, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults over 18 planning to have a stent placed for kidney stones can join. They must be able to consent and not be on steroids, have GI ulcers, or liver/kidney issues. Pregnant women, those with existing stents or certain other health problems are excluded.

Inclusion Criteria

I am planning to have a stent placed in my ureter after a procedure for kidney stones.

Exclusion Criteria

I have kidney or liver problems.

I have been taking NSAIDs regularly for the last month, but I can take daily Aspirin 81 mg.

I am currently taking steroid medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Preoperative Treatment

Participants receive a one-time intravenous injection of Ketorolac or saline prior to the ureteroscopic procedure

1 day

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for stent-related symptoms and complete symptom questionnaires

7 to 14 days

1 follow-up phone call, 1 visit (in-person) for stent removal

Follow-up

Participants are monitored for safety and effectiveness after stent removal

1 to 2 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac Trometamol

Trial Overview

The study is testing if Ketorolac, an anti-inflammatory drug given as an injection, can reduce symptoms after ureteral stent placement compared to a saline solution. It's also checking how easy it is to run the trial.

How Is the Trial Designed?

Group I: Intervention Group - Ketorlac (NSAID) Active Control 1 Intervention

Subjects will receive a one-time intravenous injection of 1 ml of Ketorlac 30 mg/ml prior to the start of the ureteroscopic procedure. After consent and during screening visit demographic information, medical/surgical history, and height and weight will be collected. On Day 0 subject will be randomized to NSAID or Saline using inclusion/exclusion criteria and the procedure data will be collected. On Day 1 subject will receive a follow up phone call and complete AUA Symptom Score, USS Questionnaire 1 and USS Questionnaire 2 and any adverse events will be assessed. These questionnaires will again be administered on the day of stent removal and again 1 to 2 months post stent removal.

Group II: Placebo Group - Normal Saline Placebo Group 1 Intervention

Subjects in the control group will receive a one-time 1 ml of 0.9% injectable normal saline prior to the start of the ureteroscopic procedure. After consent and during screening visit demographic information, medical/surgical history, and height and weight will be collected. On Day 0 subject will be randomized to NSAID or Saline using inclusion/exclusion criteria and the procedure data will be collected. On Day 1 subject will receive a follow up phone call and complete AUA Symptom Score, USS Questionnaire 1 and USS Questionnaire 2 and any adverse events will be assessed. These questionnaires will again be administered on the day of stent removal and again 1 to 2 months post stent removal.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

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]

Intraoperative administration of ketorolac significantly reduced the total morphine milligram equivalent (MME) requirements by 37% in patients undergoing ureteroscopy for nephrolithiasis, indicating its efficacy in pain management.

The study involved 94 patients and found that ketorolac was an independent predictor of lower narcotic use without increasing complication rates, suggesting it can be safely integrated into pain control protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toradol to Reduce Ureteroscopy Symptoms Trial (TRUST). Syed, JS., Khan, A., Van-Ryn, MG., et al.[2023]

The study found that after nasal inhalation of a radiolabelled ketorolac formulation, less than 0.5% of the dose reached the lungs, indicating minimal pulmonary deposition, regardless of the inhalation technique or posture used.

Most of the administered dose was deposited in the nasal cavity, with the best distribution observed when subjects were upright, and the drug cleared rapidly from the nasal cavity, with only 16-30% remaining after 10 minutes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary and nasal deposition of ketorolac tromethamine solution (SPRIX) following intranasal administration. Bacon, R., Newman, S., Rankin, L., et al.[2018]

In a double-blind study of 67 patients after upper abdominal surgery, ketorolac trometamol (10 mg) showed a significant reduction in potassium excretion compared to placebo, indicating a specific renal effect.

While ketorolac increased bleeding time, there were no adverse events related to this effect, suggesting it can be used safely in the postoperative setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ketorolac trometamol on renal function. Aitken, HA., Burns, JW., McArdle, CS., 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 review of cases, six patients experienced reversible renal insufficiency linked to short-term use of intramuscular ketorolac, with a mean recovery time of 2.3 days after stopping the medication.

The study highlights the risk of renal toxicity, particularly in patients with cardiovascular disease, suggesting that ketorolac should be used cautiously and not as a first-line pain management option in high-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal insufficiency associated with intramuscular administration of ketorolac tromethamine. Corelli, RL., Gericke, KR.[2017]

Intravenous ketorolac tromethamine provided complete pain relief for a 54-year-old man suffering from severe testicular pain due to a ureteral stone, after initial treatment with hydromorphone was ineffective.

The authors recommend using intravenous ketorolac as a first-line treatment for acute renal colic, highlighting its efficacy in managing pain when other medications may not work.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ketorolac in renal colic. Di Trolio, RN., Sing, RF., Bates, GM.[2019]

Citations

1.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK602386/

Oral Ketorolac for Renal Colic in Outpatient Settings - NCBI

We can explore the available evidence to determine whether oral ketorolac is a clinically effective option for the management of renal colic.

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0735675720311931

The analgesic effect of ketorolac addition for renal colic pain

This systematic review and meta-analysis of RCTs aims to study the analgesic efficacy of ketorolac addition in the treatment of renal colic.

3.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1111/acem.14202

Comparison of intravenous ketorolac at three doses for ...

Conclusion. Ketorolac at 10-, 20-, and 30-mg doses can produce similar analgesic efficacy in renal colic.

4.

annemergmed.com

annemergmed.com/article/S0196-0644(23)01300-8/fulltext

Atomized Intranasal Ketorolac Versus Intravenous ...

Neither IN or IV ketorolac was superior to the other for the treatment of acute renal colic, and both provided clinically meaningful reductions ...

5.

ncccp.net

ncccp.net/newsletter/the-analgesic-efficacy-of-iv-and-im-ketorolac-a-systematic-review/

The Analgesic Efficacy of IV and IM Ketorolac: A Systematic ...

Our analysis of these 14 publications found varying results, with effective analgesic ceilings ranging from 10–30 mg for both the IV and IM ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5547203/

A Triple-Blind Randomized Controlled Clinical Trial - PMC

However, recent reviews indicate that in short-term use and in typical doses, ketorolac poses little risk of renal failure [15] and does not increase the risk ...

7.

bjui-journals.onlinelibrary.wiley.com

bjui-journals.onlinelibrary.wiley.com/doi/10.1002/bco2.70038

Questionable role of opioids for analgesia in renal colic and its ...

The NHANES also identified a steady percentage increase with time, reporting kidney stone prevalence of 3%, 5% and 10% in 1980, 1994 and 2016, ...

8.

withpower.com

withpower.com/trial/ketorolac-for-kidney-stones-1afbb

Ketorolac for Kidney Stones

However, for patients receiving ketorolac for more than 5 days, there was a significant increase in the risk of acute renal failure compared to opioids, ...