Regional Anesthesia for Back Surgery

Overseen By John O'Toole, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: John O'Toole

Must not be taking: Opioids, Local anesthetics

Disqualifiers: Opioid tolerance, Indwelling pain device, Allergy to anesthetics, Chronic kidney disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 15

Duration: Up to 30 days

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how regional anesthesia can reduce the need for opioids after back surgery. Researchers are testing whether injecting a mix of bupivacaine (a numbing medication) and clonidine (which can enhance pain relief) before surgery lowers post-operative pain compared to a placebo. The trial aims to help people recovering from common lumbar spine surgeries avoid long-term opioid use. Individuals undergoing specified types of spine surgery who are not currently using opioids might be suitable candidates for this trial. As a Phase 4 trial, the research focuses on understanding how this already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are opioid tolerant, meaning you take more than 30mg of morphine equivalents daily.

What is the safety track record for Bupivacaine-Epinephrine 0.25%-1:200,000 Injectable Solution plus clonidine and Normal Saline?

Research has shown that bupivacaine with epinephrine, when combined with clonidine, is generally well-tolerated. Bupivacaine often numbs specific areas during surgery or dental work by blocking nerve signals. Epinephrine extends the numbing effect and reduces bleeding, while clonidine can enhance pain relief.

Although these medications are usually safe, some rare risks exist. For instance, reports have indicated serious heart problems when bupivacaine is used in certain situations like childbirth, though these cases are uncommon.

Most people tolerate this combination well, but discussing any concerns with a healthcare provider before joining a clinical trial is important. They can help clarify the benefits and risks for individual health. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using bupivacaine combined with clonidine for back surgery because it offers a potentially more effective pain management approach than standard options like general anesthesia or basic local anesthetics. This treatment is unique because it uses a regional anesthesia technique known as the erector spinae plane block (ESPB), which precisely targets the lumbar area to provide pain relief. The addition of clonidine, a medication that enhances the effects of bupivacaine, might extend pain relief duration, making it possible to reduce the need for opioids after surgery. This targeted approach could lead to quicker recovery times and fewer side effects compared to traditional methods.

What evidence suggests that this trial's treatments could be effective in reducing post-operative opioid requirements for back surgery?

In this trial, participants will receive either a placebo or an investigational treatment. Research has shown that a mix of bupivacaine and epinephrine for local anesthesia effectively numbs areas for surgery, providing significant pain relief. This combination reduces pain during and after procedures. Participants in the investigational arm will receive bupivacaine with epinephrine and clonidine, which extends the anesthetic effect and may reduce the need for opioid painkillers after surgery. Together, these components aim to keep patients comfortable with less reliance on opioids after back surgery. This approach could be a promising way to manage pain and lower the risk of opioid overuse. ^{2 3 6 7 8}

Who Is on the Research Team?

John O'Toole, M.D., M.S.

Principal Investigator

Rush University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 undergoing specific lumbar spinal surgeries, who can consent to participate. It's not for those with advanced kidney or liver disease, opioid tolerance, pregnancy, ongoing worker's comp cases, allergies to local anesthetics like bupivacaine or clonidine, other surgical indications besides degenerative disease, pain devices in place, or conditions affecting pain evaluation.

Inclusion Criteria

I am scheduled for a specific spine surgery involving 1 to 3 levels of my spine.

Willing and able to give consent

Exclusion Criteria

Active pregnancy

I have advanced kidney disease or liver failure.

Presence of an indwelling pain device (e.g., intrathecal opioid pump, spinal cord stimulator, dorsal root ganglion stimulator)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative

Patients receive either a placebo or ESPB with bupivacaine plus clonidine immediately prior to surgery

1 day

1 visit (in-person)

Treatment

Participants undergo minimally invasive lumbar spine surgery with perioperative pain management

Up to 30 days

Daily monitoring during inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including opioid consumption and complications

90 days

Multiple follow-up assessments at 14, 56, and 90 days postoperatively

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine-Epinephrine 0.25%-1:200,000 Injectable Solution plus clonidine
• Normal Saline

Trial Overview The study tests if adding regional anesthesia (Bupivacaine-Epinephrine plus clonidine) reduces the need for opioids after minimally invasive lumbar spine surgery. The goal is to see if this approach can help manage post-operative pain and lower long-term opioid use.

How Is the Trial Designed?

Group I: Investigational Experimental Treatment 1 Intervention

Patients will undergo regional ESPB with bupivacaine plus clonidine in the holding area of the OR immediately prior to surgery. 30mL of 0.25% bupivacaine/1:200,000 epinephrine/50mcg clonidine will be administered bilaterally (total 60ml) to the lumbar paraspinal erector spine plane using ultrasound-guidance.

Group II: Control Placebo Group 1 Intervention

Patients will receive a placebo injection of normal saline via the same ESPB technique. 30ml of normal saline will be administered bilaterally (total 60ml) to the lumbar paraspinal erector spine plane using ultrasound-guidance.

Who Is Running the Clinical Trial?

John O'Toole

Lead Sponsor

Trials

1

Recruited

130+

Published Research Related to This Trial

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 of 33 patients receiving either clonidine or epinephrine mixed with lidocaine for brachial plexus block, clonidine resulted in higher pain scores and fewer patients being pain-free for over 12 hours compared to epinephrine, indicating less effective postoperative analgesia.

Clonidine led to higher peak plasma concentrations of lidocaine occurring earlier than with epinephrine, suggesting a reduced safety margin for local anesthetic toxicity, although it may still be useful when epinephrine is contraindicated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between clonidine and epinephrine admixture to lidocaine in brachial plexus block. Gaumann, D., Forster, A., Griessen, M., et al.[2022]

In a study of 96 elderly patients undergoing lower extremity surgery, adding 0.3 mg of epinephrine to bupivacaine significantly prolonged the duration of spinal anesthesia, enhancing the regression time to the L-2 level by 29%.

The addition of epinephrine also increased the motor blockade, indicating that it can effectively enhance the anesthetic effects of bupivacaine without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of increasing amounts of epinephrine during isobaric bupivacaine spinal anesthesia in elderly patients. Racle, JP., Benkhadra, A., Poy, JY., et al.[2013]

Bupivacaine, used in various concentrations (0.25%, 0.5%, 0.75%) for different types of anesthesia, consistently provided complete sensory anesthesia for a wide range of surgical procedures, with onset times of 4 to 10 minutes and maximum effect in 15 to 35 minutes.

While there were 15 reported systemic toxic reactions, none led to lasting harm, indicating that Bupivacaine can be used safely in clinical settings, although careful monitoring is necessary, especially with higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine: a review of 11,080 cases. Moore, DC., Bridenbaugh, LD., Thompson, GE., et al.[2019]

In a study of 92 women undergoing surgery, adding clonidine to lidocaine for epidural anesthesia did not significantly change the number of segments of analgesia compared to plain lidocaine or epinephrine.

Clonidine at 10 micrograms/ml resulted in a significant decrease in heart rate, while patients receiving epinephrine experienced a notable increase in heart rate, indicating that clonidine may provide a more stable cardiovascular profile during anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of clonidine added to lidocaine solution for epidural anesthesia. Nishikawa, T., Dohi, S.[2022]

In a study of 44 patients undergoing lumbar disc surgery, the combination of epinephrine with clonidine and bupivacaine in epidural anesthesia resulted in less decrease in arterial pressure and heart rate compared to clonidine alone.

The use of low-dose epidural epinephrine helps stabilize arterial pressure during combined epidural and general anesthesia, suggesting it may enhance the safety profile of the anesthesia technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of epinephrine associated to an epidural clonidine-bupivacaïne mixture during combined lumbar epidural and general anesthesia. Senard, M., Ledoux, D., Darmon, PL., et al.[2013]

In a study of 100 healthy parturients, adding a low dose of clonidine to an epidural mixture of bupivacaine, epinephrine, and sufentanil significantly improved the quality and duration of labor analgesia compared to other combinations.

The side effects associated with clonidine were minimal, with manageable hypotension and mild sedation that did not cause fetal distress, indicating it is a safe addition to epidural analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clonidine added to bupivacaine-epinephrine-sufentanil improves epidural analgesia during childbirth. Claes, B., Soetens, M., Van Zundert, A., et al.[2019]

Adding low-dose clonidine to hyperbaric ropivacaine significantly prolongs the duration of sensory and motor blockade as well as postoperative pain relief in patients undergoing lower limb or abdominal surgeries, based on a study of 90 patients.

While the combination improves anesthesia duration, it also increases the risk of intra-operative hypotension and bradycardia, which can be managed with standard clinical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of adding low-dose clonidine to intrathecal hyperbaric ropivacaine: A randomized double-blind clinical trial. Kakunje, R., Sethuramachandran, A., Parida, S., et al.[2020]

In a study of 50 patients with moderate hypertension undergoing tooth extraction, the combination of lidocaine with clonidine provided similar anesthetic effects to lidocaine with epinephrine, but with better hemodynamic stability.

Patients receiving lidocaine with clonidine experienced significantly less postoperative pain and required fewer analgesics compared to those receiving lidocaine with epinephrine, suggesting clonidine may be a safer alternative for hypertensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is clonidine an adequate alternative to epinephrine as a vasoconstrictor in patients with hypertension? Patil, PM., Patil, SP.[2013]

In a study involving 20 patients undergoing elective urologic surgery, the addition of epinephrine to bupivacaine did not change the maximum level of sensory blockade achieved, which was similar in both groups (T7 and T8).

However, the group receiving bupivacaine with epinephrine experienced significant increases in cardiac output, stroke volume, and end diastolic volume shortly after administration, highlighting the systemic effects of epinephrine, while the plain bupivacaine group showed a significant decrease in ejection fraction after 15 minutes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic monitoring in epidural blockade: cardiovascular effects of 20 ml 0.5% bupivacaine with and without epinephrine. Kerkkamp, HE., Gielen, MJ.[2013]

The combination of perioperative clonidine and bupivacaine for pain management during and after above-knee amputation resulted in very low postoperative pain scores (mean of 1.2 out of 10) and minimal opioid use (only 10 mg of oxycodone required).

Importantly, the patient did not experience any incidents of hypotension, bradycardia, or sedation during the infusion, and there was no report of stump or phantom limb pain for 12 months following the surgery, suggesting a safe and effective pain management strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of postoperative perineural infusion of bupivacaine and clonidine after lower extremity amputation in preventing phantom limb and stump pain. Madabhushi, L., Reuben, SS., Steinberg, RB., et al.[2013]

In a study of 435 patients, bupivacaine (0.75% in 8.25% dextrose) demonstrated superior efficacy compared to tetracaine for spinal anesthesia, with only one unsatisfactory anesthesia case in the bupivacaine group versus 19 in the tetracaine group for the lower dose.

Bupivacaine was found to be a safe and reliable option for spinal anesthesia, although tetracaine provided longer motor blockade; adding epinephrine to either anesthetic significantly extended their duration of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal anesthesia: bupivacaine compared with tetracaine. Moore, DC.[2013]

In a study involving 29 ASA II-III patients undergoing peripheral vascular surgery, the addition of epinephrine or clonidine to spinal bupivacaine significantly prolonged the duration of sensory blockade compared to bupivacaine alone, with sensory blockade lasting approximately 230 minutes in the combination groups versus 170 minutes in the bupivacaine-only group.

Despite the prolonged sensory blockade, the study found no significant differences in the plasma concentrations of bupivacaine among the three groups, indicating that epinephrine and clonidine do not reduce the absorption of bupivacaine into the bloodstream.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of epinephrine and clonidine on plasma concentrations of spinal bupivacaine. Boico, O., Bonnet, F., Mazoit, JX.[2019]

Citations

1. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d0d51133-882c-4f9e-ba1c-f037226305a1

MARCAINE WITH EPINEPHRINE- bupivacaine hydrochloride ... There have been reports of cardiac arrest with difficult resuscitation or death during use of MARCAINE for epidural anesthesia in obstetrical patients. In most ...

2. mayoclinic.org mayoclinic.org/drugs-supplements/bupivacaine-and-epinephrine-injection-route/description/drg-20452206

Bupivacaine and epinephrine (injection route) Bupivacaine and epinephrine combination injection is used to numb an area of your body during surgery or other procedures, childbirth, or dental work.

3. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=67578b56-7540-487e-1fba-481255620e78&audience=consumer

bupivacaine hydrochloride and epinephrine bitartrate injection ... Use the lowest dosage of MARCAINE / MARCAINE WITH EPINEPHRINE that results in effective anesthesia to avoid high plasma levels and serious adverse effects.

4. mountainside-medical.com mountainside-medical.com/collections/epinephrine-for-injection/products/marcaine-bupivacaine-hydrochloride-with-epinephrine-1-200-000-for-injection-0-25-multi-dose-50ml-vial?srsltid=AfmBOooHDzl6JmAknFahjj2L9SapTUZTl3GklNWsYHO-9O17sleYPEtg

Marcaine w/ Epinephrine: 125mg Pain & Anesthesia Relief Marcaine (Bupivacaine Hydrochloride) 125 mg/50 mL with Epinephrine 1:200000 provides effective local anesthesia and pain relief in surgeries.

5. va.gov va.gov/formularyadvisor/drugs/4004274-BUPIVACAINE--EPINEPHRINE-INJ-SOLN

BUPIVACAINE/ EPINEPHRINE INJ,SOLN BUPIVACAINE/ EPINEPHRINE INJ,SOLN (Formulary Item) is an item listed by VA within the class LOCAL ANESTHETICS,INJECTION. BUPIVACAINE/ EPINEPHRINE INJ,SOLN ...

6. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=67578b56-7540-487e-1fba-481255620e78

MARCAINE- bupivacaine hydrochloride injection ... - DailyMed WARNING: RISK OF CARDIAC ARREST WITH USE OF MARCAINE IN OBSTETRICAL ANESTHESIA. There have been reports of cardiac arrest with difficult resuscitation or ...

7. clintpharmaceuticals.com clintpharmaceuticals.com/1001-0002-0005-0000-marcaine-bupivicaine-w-epi.html

Marcaine / Bupivicaine w/Epi Injectable Marcaine (Bupivicaine) with Epinephrine, used by Practitioners to reduce pain locally or on specific nerve pathways, is available in Ampules, ...

8. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=76bb1e84-6032-4bb4-9b79-596542f5d05d

MARCAINE- bupivacaine hydrochloride injection, solution MARCAINE / MARCAINE WITH EPINEPHRINE is indicated in adults for the production of local or regional anesthesia or analgesia for surgery, dental and oral surgery ...