Ketorolac for Blood Vessel Function

(VDR Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Milton S. Hershey Medical Center

Must not be taking: Cardiovascular, Nervous system, NSAIDs

Disqualifiers: Chronic diseases, Pregnancy, Claustrophobia, others

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

Compensation: Varies

Number of Visits: 1

Duration: 3-4 hours

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how ketorolac, a non-steroidal anti-inflammatory drug (NSAID), affects blood vessel function. Researchers seek to determine if ketorolac alters nerve activity related to blood vessel stretching in the limbs. Participants will receive either ketorolac or a placebo to compare effects. Ideal candidates are healthy individuals without chronic medical conditions who have not recently taken NSAIDs. As an Early Phase 1 trial, participants will assist researchers in understanding how ketorolac works in the human body.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications that affect your cardiovascular or nervous system to participate in this trial.

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

Research shows that ketorolac tromethamine is typically used for short-term pain relief, often after surgery. As an intravenous NSAID, it is administered through a vein. Studies indicate that use should not exceed five days, as longer use can increase the risk of heart problems, kidney issues, and stomach ulcers.

Ketorolac can affect blood clotting, making it unsafe for individuals with certain bleeding disorders or those at higher risk of bleeding. When used as directed for short periods, ketorolac is generally safe and well-tolerated for most people. However, following medical advice and monitoring for any side effects is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for blood vessel function issues focus on improving blood flow or reducing inflammation through long-term medication use. Ketorolac tromethamine stands out because it is a nonsteroidal anti-inflammatory drug (NSAID) that is being tested for its ability to rapidly enhance blood vessel function. Researchers are excited because it could offer quicker results by directly targeting and reducing inflammation in the blood vessels, potentially improving function more efficiently than traditional treatments.

What evidence suggests that ketorolac might be an effective treatment for blood vessel function?

Research shows that ketorolac, a type of pain reliever, affects blood vessel function. Studies have found that ketorolac increases blood flow to the skin by blocking an enzyme involved in inflammation. This trial will compare the effects of ketorolac with a saline control on blood vessel function. Participants in the ketorolac arm will receive ketorolac tromethamine infusions, while those in the control arm will receive saline infusions. Additionally, research has shown that ketorolac reduces nerve activity when blood vessels are stretched, which can influence blood pressure. These findings suggest that ketorolac could help manage blood vessel reactions, although more research is needed to confirm its effects in larger human studies. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 21-35, fluent in English, weighing over 50 kg, and without chronic medical conditions. Participants must not have taken NSAIDs recently or be allergic to them. Pregnant women, individuals with high blood pressure or metal implants, and those on certain medications are excluded.

Inclusion Criteria

I understand the study and can agree to participate.

My medical history and physical exam meet the trial's requirements.

Any race or ethnicity

Exclusion Criteria

Subjects with ferromagnetic metal implants

Subjects who are claustrophobic

I am either younger than 21 or older than 35.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo wrist-to-elbow occlusion procedure with ketorolac tromethamine and saline infusions to study the venous distension reflex

3-4 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac Tromethamine
• Saline Control
• Wrist-to-elbow (W-E) Occlusion

Trial Overview The study tests how ketorolac tromethamine (a painkiller) affects the body's response to vein stretching in the arm. It compares this drug's effect with a saline solution using MRI scans to observe changes in vein size during the process.

How Is the Trial Designed?

Group I: Ketorolac Experimental Treatment 2 Interventions

The Wrist-to-Elbow occlusion procedure will be performed followed by 2 ketorolac tromethamine + saline infusions into the occluded arm.

Group II: Control Placebo Group 2 Interventions

The Wrist-to-Elbow occlusion procedure will be performed followed by 2 saline only infusions into the occluded arm.

Ketorolac Tromethamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Toradol for:

• Moderate to severe pain
• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Menstrual disorders
• Headaches

Approved in European Union as Ketorolac for:

• Moderate to severe pain
• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Menstrual disorders
• Headaches

Approved in Canada as Ketorolac for:

• Moderate to severe pain
• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Menstrual disorders
• Headaches

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Published Research Related to This Trial

A case study of a 31-year-old man revealed that excessive use of ketorolac tromethamine (Acula) after PRK led to corneal ulceration and perforation, necessitating surgical intervention.

The findings highlight the importance of proper patient education regarding the use of topical NSAIDs post-surgery to prevent complications like corneal damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal ulceration and perforation with ketorolac tromethamine (Acular) use after PRK. Mian, SI., Gupta, A., Pineda, R.[2019]

In a randomized study involving patients after extensive colonic resections, the combination of intramuscular ketorolac and patient-controlled intravenous morphine provided equal pain relief compared to morphine alone, without increasing side effects.

The use of ketorolac significantly reduced the need for narcotics by an average of 45%, making it a valuable option for patients at risk of narcotic-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac and patient controlled analgesia in the treatment of postoperative pain. Cataldo, PA., Senagore, AJ., Kilbride, MJ.[2013]

A study on healthy dogs showed that ketorolac tromethamine significantly reduces plasma levels of the inflammatory compound PGE2 after both intravenous and oral administration, indicating its effectiveness as a potent analgesic.

The decrease in PGE2 levels is significant but reversible, suggesting that while ketorolac is effective in pain relief, it may also contribute to its potential for gastric and renal toxicity due to its impact on endogenous compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma prostaglandin E2 concentrations after single dose administration of ketorolac tromethamine (Toradol) in dogs. Pasloske, K., Burger, J., Conlon, P.[2018]

In a study of 100 male patients undergoing laparoscopic inguinal hernia repair, the combination of ketorolac tromethamine and dezocine significantly reduced fluctuations in heart rate and mean arterial pressure during recovery compared to control, indicating better hemodynamic stability.

Patients receiving the combination treatment also reported lower pain scores and higher sedation levels post-surgery, suggesting enhanced analgesic and sedative effects without increasing the risk of adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ketorolac tromethamine combined with dezocine prior administration on hemodynamics and postoperative analgesia in patients undergoing laparoscopic hernia repair. Wu, Y., Cai, Z., Li, Y., et al.[2023]

A study involving 27 healthy Mexican adults found that two sublingual formulations of 30-mg ketorolac were bioequivalent, meaning they had similar absorption rates and effectiveness in the body.

Both formulations were well tolerated, with only mild adverse events reported, indicating that they are safe for use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of two sublingual formulations of ketorolac tromethamine 30 mg: a randomized, open-label, single-dose, two-period crossover comparison in healthy Mexican adult volunteers. Galán-Herrera, JF., Poo, JL., Maya-Barrios, JA., et al.[2014]

A single dose of ketorolac significantly prolonged bleeding times and reduced platelet aggregation in a rat model, indicating its strong anti-thrombotic effects immediately after administration.

Despite its initial effectiveness in preventing thrombosis, ketorolac was ineffective for long-term prevention of microarterial thrombosis, and its use may pose a risk of bleeding complications in postoperative patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ketorolac tromethamine (Toradol) on a functional model of microvascular thrombosis. Buckley, RC., Davidson, SF., Das, SK.[2019]

Adding ketorolac tromethamine to lidocaine for ankle blocks significantly improves the quality and duration of pain relief after foot surgery compared to using lidocaine alone or with intravenous ketorolac.

The study found that ketorolac remains chemically stable when mixed with local anesthetics, indicating it can be safely used in this manner without altering its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative analgesia after peripheral nerve block for podiatric surgery: clinical efficacy and chemical stability of lidocaine alone versus lidocaine plus ketorolac. Reinhart, DJ., Stagg, KS., Walker, KG., et al.[2019]

In a retrospective study of breast surgery patients over three years, ketorolac did not significantly increase the risk of postoperative hematoma formation, with rates of 3.5% in those receiving ketorolac compared to 2.5% in those who did not.

The overall hematoma rate for the entire cohort was 2.8%, suggesting that ketorolac can be safely used for postoperative pain control without raising concerns about bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? Nguyen, BN., Barta, RJ., Stewart, CE., et al.[2021]

In a multicenter study involving patients with moderate to severe inflammation after cataract surgery, ketorolac tromethamine 0.5% was significantly more effective than a placebo in reducing inflammation and associated symptoms like pain and photophobia.

The treatment was found to be safe, with no significant differences in visual acuity or adverse events compared to the placebo, indicating that ketorolac is a reliable option for managing post-surgical inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial. Heier, J., Cheetham, JK., Degryse, R., et al.[2019]

In a study of 4086 patients undergoing elective neurosurgery, those who received ketorolac had a significantly lower incidence of symptomatic intracranial hemorrhage (ICH) at 0.5% compared to 1.3% in those who did not receive the drug, suggesting a potential protective effect against bleeding.

Despite the lower observed risk of ICH in patients taking ketorolac, the adjusted odds ratio was close to 1, indicating that the findings may not be conclusive enough to definitively establish the safety of ketorolac in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial hemorrhage requiring surgery in neurosurgical patients given ketorolac: a case-control study within a cohort (2001-2010). Magni, G., La Rosa, I., Melillo, G., et al.[2022]

In a study involving 200 patients undergoing photorefractive keratectomy, topical ketorolac tromethamine 0.5% was found to provide significantly greater pain relief compared to its vehicle, with patients experiencing less pain intensity and a longer time before needing additional pain medication.

The ketorolac group also reported fewer side effects, such as sleep difficulties and ocular discomfort, and overall, the treatment was deemed safe with minimal adverse events, indicating its efficacy and safety for post-surgery pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic efficacy and safety of ketorolac after photorefractive keratectomy. Ketorolac Study Group. Rajpal, RK., Cooperman, BB.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2763840/

Ketorolac alters blood flow during normothermia but not ... We found that in middle-aged skin localized non-isoform-specific COX inhibition with ketorolac significantly increased thermoneutral skin blood flow, suggesting ...

2. withpower.com withpower.com/trial/early-phase-1-dilatation-pathologic-7-2019-5cbb8

Ketorolac for Blood Vessel Function (VDR Trial) A single dose of ketorolac significantly prolonged bleeding times and reduced platelet aggregation in a rat model, indicating its strong anti-thrombotic effects ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK545172/

Ketorolac - StatPearls - NCBI Bookshelf Ketorolac, a nonsteroidal anti-inflammatory drug, is an option for the management of acute moderate-to-severe pain.

4. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.122.20506

Effect of Cyclooxygenase Inhibition on Peripheral Venous ... The presented data show that cyclooxygenase blockade attenuates the responses in MSNA and blood pressure to peripheral venous distension reflex.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053077013004242

Is Ketorolac Safe for Use After Cardiac Surgery? Ketorolac-treated patients were younger, had better preoperative renal function, and underwent less complex operations compared with non-ketorolac patients.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/019645s019lbl.pdf

TORADOL (ketorolac tromethamine tablets) Rx only ... TORADOL inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, ...

7. webmd.com webmd.com/drugs/2/drug-3919/ketorolac-oral/details

Ketorolac (Toradol) – Uses, Side Effects, and More Ketorolac is commonly used for moderately severe acute pain that needs strong pain relief, often after surgery.

8. mayoclinic.org mayoclinic.org/drugs-supplements/ketorolac-oral-route-injection-route/description/drg-20066882

Ketorolac (oral route, injection route) - Side effects & dosage Ketorolac is used to relieve moderately severe pain, usually pain that occurs after an operation or other painful procedure.

9. sprix.com sprix.com/

SPRIX® | Official Site for HCPs SPRIX® (ketorolac tromethamine) is indicated in adult patients for the short term (up to 5 days) management of moderate to moderately severe pain that requires ...