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?

The study objective of this project is to examine the mechanisms of the venous distension reflex (VDR) in humans. We hypothesize that COX blockade with ketorolac tromethamine, an intravenous NSAID, will attenuate the muscle sympathetic nerve activity (MSNA) response to limb venous distension. To gain further insight into whether the COX byproducts directly stimulate chemically-sensitive afferents, or enable venodilation and indirectly evoke afferent stimulation, we will measure vein size using 3T MRI during venous distention with and without ketorolac infusions.

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 ketorolac generally safe for humans?

Ketorolac is generally considered safe for humans, but there are some risks. It has been associated with bleeding in certain surgeries and eye complications when used in high doses. Always consult with a healthcare provider for personalized advice. ^{1 2 3 4 5}

How does the drug ketorolac tromethamine differ from other treatments for blood vessel function?

Ketorolac tromethamine is unique because it is a nonsteroidal anti-inflammatory drug (NSAID) that not only helps with pain relief but also strongly inhibits platelet aggregation, which can affect blood clotting. This dual action may influence blood vessel function differently compared to other treatments that do not have these combined effects. ^{5 6 7 8 9}

What data supports the effectiveness of the drug Ketorolac Tromethamine for blood vessel function?

Ketorolac Tromethamine is known for its strong pain-relieving effects and ability to reduce the need for narcotics after surgery, as shown in studies where it decreased narcotic requirements by up to 45%. It also has anti-inflammatory properties and can inhibit platelet aggregation, which might be relevant for blood vessel function. ^{2 5 9 10 11}

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.

Any race or ethnicity

Fluent in written and spoken English

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 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]

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]

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]

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 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]

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]

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 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]

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]

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 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]

Citations

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

Effects of ketorolac tromethamine (Toradol) on a functional model of microvascular thrombosis. [2019]

2. United States 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. [2023]

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

Ketorolac and patient controlled analgesia in the treatment of postoperative pain. [2013]

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

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? [2021]

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

Analgesic efficacy and safety of ketorolac after photorefractive keratectomy. Ketorolac Study Group. [2022]

6. United States 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. [2019]

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

Corneal ulceration and perforation with ketorolac tromethamine (Acular) use after PRK. [2019]

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

Intracranial hemorrhage requiring surgery in neurosurgical patients given ketorolac: a case-control study within a cohort (2001-2010). [2022]

9. England 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. [2019]

10. United States 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. [2014]

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

Plasma prostaglandin E2 concentrations after single dose administration of ketorolac tromethamine (Toradol) in dogs. [2018]