Ketamine for Acute Pain

Overseen By Christy Wise, B.A.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Summa Health System

Must not be taking: Opiates, Alcohol, Others

Disqualifiers: Pregnant, Unstable heart disease, Others

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

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

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This will be an intent to treat prospective, double blind, double-dummy, randomized trial. Our primary objective is the reduction of side effects of sub dissociative dose ketamine given by slow intravenous (IV) infusion over 30 minutes vs. 15 minutes in the treatment of acute, severe pain in Emergency Department (ED) patients. The secondary objective will be to maintain adequate pain control (as defined by a Visual Analog Scale (VAS) score of ≤ 5cm) at 30 minutes for both groups.

Will I have to stop taking my current medications?

The trial requires that you have not used fentanyl within 60 minutes or other opiates within 4 hours before joining. Chronic use of opiates is also not allowed. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

How does the drug ketamine differ from other treatments for acute pain?

Ketamine is unique for acute pain treatment because it can be administered in various ways, such as epidurally, intramuscularly, or orally, and it provides pain relief without causing respiratory depression, a common side effect of opiates. Additionally, its S(+)-isomer is more potent than the racemic form, offering effective pain relief at lower doses. ^{1 2 3 4 5}

Research Team

Michael Pallaci, DO, FACEP

Principal Investigator

Summa Health System

Eligibility Criteria

This trial is for adults over 18 in the Emergency Department with acute, severe pain from conditions like abdominal or musculoskeletal pain. They must be alert, oriented, and able to consent. Excluded are pregnant or breastfeeding individuals, those with altered mental status or unstable vitals, recent drug/alcohol use, certain psychiatric conditions, recent analgesic use, chronic opiate users, and those with specific heart diseases.

Inclusion Criteria

I experience pain in my abdomen, back, sides, muscles, or chest due to injury.

My pain level is at least a 5 out of 10.

I am fully aware of who I am, where I am, and the current time.

Exclusion Criteria

I regularly use strong painkillers like fentanyl.

I haven't used fentanyl in the last hour or other painkillers in the last 4 hours.

I have a history of serious heart problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive low dose ketamine infusion for pain management over 15 or 30 minutes

1 day

1 visit (in-person)

Follow-up

Participants are monitored for side effects and pain control using VAS and SERSDA scales

90 minutes

1 visit (in-person)

Treatment Details

Interventions

• Ketamine

Trial Overview The study tests if a low dose of Ketamine given slowly through an IV over 30 minutes reduces side effects compared to a faster infusion over 15 minutes while still controlling severe pain effectively in emergency situations.

Participant Groups

Group I: Ketamine 30 Minutes Experimental Treatment 1 Intervention

Participants receive 0.25mg/kg Ketamine dose intravenous for pain over 30 minutes.

Group II: Ketamine 15 Minutes Active Control 1 Intervention

Participants receive 0.25mg/kg Ketamine dose intravenous for pain over 15 minutes.

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

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Summa Health System

Lead Sponsor

Trials

31

Recruited

3,200+

Findings from Research

In a study involving 7 patients with severe pain, epidural administration of 4 mg ketamine resulted in pain relief for all participants, with effects lasting from 30 minutes to over 6 hours.

Ketamine's use in this context showed no adverse side effects or neurological damage, and it presents a safer alternative to opioids, as it is unlikely to cause respiratory depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidural ketamine. A preliminary report. Mankowitz, E., Brock-Utne, JG., Cosnett, JE., et al.[2014]

In a study involving six healthy volunteers, both intramuscular (i.m.) and oral ketamine at a dose of 0.5 mg/kg effectively increased pain thresholds and prolonged pain-free exercise during a tourniquet test.

The i.m. route required a higher plasma concentration of ketamine (150 ng/ml) for analgesia compared to the oral route (40 ng/ml), suggesting that oral ketamine may be effective due to higher levels of its metabolite norketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and analgesic effects of i.m. and oral ketamine. Grant, IS., Nimmo, WS., Clements, JA.[2022]

In a study of 69 gynecological surgery patients, low dose ketamine (0.15 mg/Kg) administered preoperatively did not provide a preemptive analgesic effect, as indicated by similar pain scores at rest compared to placebo.

However, patients receiving ketamine postoperatively experienced less pain upon movement on the fifth day and required less morphine in the first 6 hours, suggesting that while preemptive use is ineffective, postoperative ketamine can still improve pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of low-dose intravenous ketamine in postoperative analgesia for hysterectomy and adnexectomy]. Gilabert Morell, A., Sánchez Pérez, C.[2013]

Intramuscular administration of ketamine provides rapid absorption with a high bioavailability of 93%, making it an effective route for achieving analgesic effects in healthy volunteers.

Oral administration of ketamine results in only 17% absorption due to extensive first-pass metabolism, leading to minimal pain relief, highlighting the importance of administration route for efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. Clements, JA., Nimmo, WS., Grant, IS.[2021]

S(+)-Ketamine, at half the dose of ketamine racemate, provides similar analgesic effects while causing fewer adverse effects on cognitive functions and a smaller increase in heart rate, making it a promising option for emergency medicine.

In a study involving 16 healthy volunteers, S(+)-ketamine resulted in significantly less anterograde amnesia compared to ketamine racemate, suggesting it may be safer for use in situations where maintaining cognitive function is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses]. Pfenninger, E., Baier, C., Claus, S., et al.[2013]

References

1. South Africa pubmed.ncbi.nlm.nih.gov

Epidural ketamine. A preliminary report. [2014]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and analgesic effects of i.m. and oral ketamine. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

[Effect of low-dose intravenous ketamine in postoperative analgesia for hysterectomy and adnexectomy]. [2013]

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

Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

[Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses]. [2013]