Bupivacaine vs BKK Combination for Pain Management After CIED Procedures

Not yet recruiting at 2 trial locations

Overseen By Donita Atkins

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kansas City Heart Rhythm Research Foundation

Disqualifiers: Allergies, Pregnancy, Prisoners, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two different pain relief treatments for individuals receiving cardiac implantable electronic devices, such as pacemakers. One group receives bupivacaine, a common numbing medicine. The other group tries a new combination of bupivacaine, ketorolac (a pain reliever), and ketamine (an anesthetic). The trial aims to determine if this combination better reduces pain during and after the procedure. It seeks participants who are receiving a new cardiac device and are open to trying a new pain treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new pain treatment combination.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that bupivacaine is generally safe when used correctly, with only minor side effects. It is commonly used in surgeries and procedures to manage pain. The combination of bupivacaine, ketorolac, and ketamine (BKK) represents a newer method. Some studies have explored BKK for abdominal surgeries and found it can effectively manage pain without requiring opioids.

Bupivacaine alone has a strong safety record. Although research on the BKK combination continues, no major safety concerns have emerged so far. This trial is in an early stage, focusing on learning more about the safety and tolerability of the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Bupivacaine-Ketorolac-Ketamine (BKK) combination for pain management after cardiac implantable electronic device (CIED) procedures because it offers a multi-faceted approach to pain relief. Unlike standard treatments that typically focus on a single mechanism, the BKK combination utilizes the anesthetic properties of bupivacaine, the anti-inflammatory benefits of ketorolac, and the NMDA receptor antagonism of ketamine. This combination could potentially provide more comprehensive pain control by targeting different pathways, which might reduce the need for opioids and their associated side effects. Additionally, the use of ketamine may help manage both acute and lingering pain, offering a broader spectrum of pain management.

What evidence suggests that this trial's treatments could be effective for pain management after CIED procedures?

Research has shown that Bupivacaine helps manage pain after surgeries like breast reduction and back surgery. In this trial, participants will join one of two treatment arms: one receiving Bupivacaine alone and another receiving a combination of Bupivacaine with Ketorolac and Ketamine (BKK). Researchers believe the BKK combination relieves pain during and after surgery more effectively than Bupivacaine alone. Previous studies found that this combination can manage pain effectively without opioids. Ketamine, in particular, works well with Bupivacaine to reduce pain. Although limited research exists on using BKK for heart device procedures, its components have shown promise in other surgeries. ^{1 3 4 5 6}

Who Is on the Research Team?

Dhanunjaya Lakkireddy

Principal Investigator

Kansas City Heart Rhythm Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are getting a new cardiac implantable electronic device (like an ICD or pacemaker) and want to participate. It's not for pregnant/breastfeeding individuals, prisoners, those under 18, anyone allergic to the drugs being tested, or patients considered unstable for the study.

Inclusion Criteria

I am willing to participate in the study.

I am either male or female.

I am older than 18 years.

Exclusion Criteria

Pregnant or breastfeeding patients

I am under 18 years old.

Prisoners

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either Bupivacaine alone or a combination of Bupivacaine-Ketorolac-Ketamine (BKK) during the CIED insertion procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for pain intensity, quality of life, and adverse effects post-procedure

1 week

1-2 visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine
• Ketamine
• Ketorolac

Trial Overview The study is testing if a mix of Bupivacaine-Ketorolac-Ketamine (BKK) can better manage pain during and after surgery compared to just Bupivacaine alone in patients receiving heart-related implants.

How Is the Trial Designed?

Group I: Bupivacaine-Ketorolac-Ketamine (BKK) Combination Experimental Treatment 1 Intervention

This is the intervention group of patients receiving 20 cc combination of BKK (Bupivacaine HCl 60 mg \[3 mg/mL\], Ketorolac Tromethamine 24 mg \[1.2mg/mL\], Ketamine HCl 24 mg \[1.2 mg/mL\]).The dose and number of doses of the medicines will be adjusted as per discretion of the operator.

Group II: Bupivacaine Alone Experimental Treatment 1 Intervention

This is the control group of patients receiving 20 cc of 0.5% bupivacaine (Bupivacaine HCL 100 mg \[5mg/ml\] alone. The dose and number of doses of the medicines will be adjusted as per discretion of the operator.

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

Approved in United States as Marcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Approved in European Union as Marcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Approved in Canada as Sensorcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Who Is Running the Clinical Trial?

Kansas City Heart Rhythm Research Foundation

Lead Sponsor

Trials

30

Recruited

14,000+

Cardiac Arrhythmia Service, Loma Linda University Health, Loma Linda, CA

Collaborator

Trials

1

Recruited

200+

Published Research Related to This Trial

In a study of 37 patients undergoing breast reduction surgery, the use of the long-acting local anesthetic bupivacaine (Sensorcaine) significantly reduced the time to discharge from the postanesthesia care unit, averaging 2.9 hours compared to 3.8 hours for the placebo group.

Patients who received Sensorcaine reported lower pain levels and required significantly less narcotic medication post-surgery, taking an average of 3.5 tablets compared to 6.4 tablets in the control group, indicating its efficacy in managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Sensorcaine significantly improves postoperative pain management in outpatient reduction mammaplasty. Culliford, AT., Spector, JA., Flores, RL., et al.[2021]

Bupivacaine hydrochloride (Marcaine) is highlighted for its increased duration of action compared to other local anesthetics, making it particularly useful in oral surgery.

It also has a favorable potency to toxicity ratio, suggesting that it provides effective pain relief with a lower risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine: a review. Babst, CR., Gilling, BN.[2018]

Bupivacaine (Marcaine) is effective for epidural analgesia in obstetrics, providing excellent sensory block with minimal impact on motor function and few side effects for both mothers and newborns.

When used at concentrations below 0.5%, and with careful dosing during labor, the risk of side effects and toxicity is low, and significant effects on newborns are rare due to the drug's high protein binding limiting its transfer across the placenta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of Marcaine in obstetrical analgesia]. Seebacher, J., Chareire, F., Galli-Douant, P., et al.[2013]

Bupivacaine with a vasoconstrictor has a shorter onset time for local anesthesia compared to bupivacaine without a vasoconstrictor, but the duration of anesthesia is longer without the vasoconstrictor.

Using bupivacaine without a vasoconstrictor resulted in lower postoperative pain levels and better blood circulation, which is beneficial for the osseointegration of dental implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical parameters of the local anesthetic effects of bupivacaine applied with and without a vasoconstrictor in oral implantology. Duka, M., Lazić, Z., Stamatović, N., et al.[2019]

In a study involving 30 patients, two forms of 0.5% bupivacaine hydrochloride (Anecaine and Marcaine) were compared for epidural anesthesia, revealing differences in how quickly and effectively they provided pain relief.

Anecaine showed a shorter onset of analgesia at the catheter site but a delayed effect in peripheral areas compared to Marcaine, indicating that even the same active ingredient can behave differently based on the manufacturer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical trial of the use of 2 forms of bupivacaine hydrochloride (Anecaine and Marcaine) for epidural anesthesia]. Kozlov, SP., Vashchinskaia, TV., Svetlov, VA.[2013]

Citations

1. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05575999/

Trial | NCT05575999 An opioid free combination of Bupivacaine-Ketorolac-Ketamine (BKK) is thought to be effective in alleviating perioperative and postoperative pain. Timeline.

2. withpower.com withpower.com/trial/phase-1-pain-management-9-2022-92983

Bupivacaine vs BKK Combination for Pain Management ... Research shows that Bupivacaine (also known as Marcaine or Sensorcaine) is effective in managing pain after surgeries, such as breast reduction and lumbar disc ...

3. clinicaltrial.be clinicaltrial.be/en/details/14152?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

Effectiveness of Bupivacaine, Ketorolac, Ketamine, vs Bup... An opioid free combination of Bupivacaine-Ketorolac-Ketamine (BKK) is thought to be effective in alleviating perioperative and postoperative ...

4. ichgcp.net ichgcp.net/clinical-trials-registry/NCT05575999

Bupivacaine alone OR Bupivacaine-Ketorolac-Ketamine (BKK ... It is hypothesized that the combination of Bupivacaine-Ketorolac-Ketamine (BKK) is more effective in alleviating perioperative and postoperative pain as ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5996673/

Ketamine and bupivacaine attenuate post-operative pain ... Furthermore, ketamine has been reported to be more efficient when combined with bupivacaine and a femoral nerve block (19). Bupivacaine is ...

6. ctv.veeva.com ctv.veeva.com/study/effectiveness-of-bupivacaine-ketorolac-ketamine-vs-bupivacaine-alone-in-reducing-postoperative-po

Effectiveness of Bupivacaine, Ketorolac, Ketamine, vs ... It is hypothesized that the combination of Bupivacaine-Ketorolac-Ketamine (BKK) is more effective in alleviating perioperative and postoperative pain as ...