Sub-Dissociative Ketamine and Fentanyl to Treat Moderate to Severe Pain

NCT ID: NCT03959852

Last Updated: 2020-09-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-18
• Study Completion Date: 2020-06-05

Brief Summary

The objective of this study is to evaluate the potential opioid-sparing effect associated with the novel combination of fentanyl and sub-dissociative ketamine in adult patients with moderate to severe pain in the emergency department.

Detailed Description

Pain is a very common complaint in the emergency department (ED). The use of opioids to treat moderate to severe pain has increased over the last decade as well as the number of opioid related deaths. In 1999 to 2016, more than 630,000 people died from a drug overdose. Treatment for acute pain has been assessed in the ED, with review of several different pain medications. Sub-dissociative ketamine (SDK) has become a valuable treatment option for acute pain and in recent years, has been of increased interest due to the growing concerns regarding opioid abuse and opioid shortage in the United States. Sub-dissociative ketamine, an NMDA receptor antagonist, has been studied in dose ranges of 1-4.5 mg/kg for dissociative sedation, as well as dose ranges of 0.1-0.3 mg/kg to treat pain. The onset of action for an IV dose of 2 mg/kg has been studied, with onset usually within 30 seconds after injection and anesthetic effect lasting 5-10 minutes. Common side effects include elevated blood pressure, diplopia or nystagmus, nausea and vomiting. More rare and more severe side effects in dissociative doses include respiratory depression, emergency phenomenon, tonic and clonic movements, and anaphylaxis. However, these were rarely, if ever seen, findings in sub-dissociative doses. Several studies indicate that SDK is a safe and effective alternative to opioids for patients with complaints of moderate to severe pain that provides adequate analgesic effect by itself. In particular, several studies have compared SDK versus morphine, particularly looking at pain in individuals with abdominal pain, flank pain, low back pain or musculoskeletal pain, and acute fractures. SDK has also shown to decrease opioid consumption and the need for rescue analgesia. The studies showed that that there was no difference in average pain scores, but the amount of morphine required was significantly decreased. SDK has proven to be a safe alternative, but the side effects, although short, make it less desirable to use. To the investigator's knowledge, there has never been a study focusing on the use of combination fentanyl and SDK. Fentanyl, an opioid agonist, has been studied in low dose forms of 2 mcg/kg for pain, moderate dose forms of 2-20 mcg/kg for major surgical procedures, and high dose forms of 20-50 mcg/kg for orthopedic and open heart surgeries. Onset of action is almost immediate when given IV, and maximal effect of the drug may take several minutes. The usual duration of action is 30-60 minutes. Common side effects include hypertension, hypotension, dizziness, blurred vision, nausea, vomiting and laryngospasm. Serious side effects included respiratory depression, apnea, rigidity, bradycardia, serotonin syndrome, adrenal insufficiency, and if left untreated could cause cardiac arrest and circulatory depression. There have been several combination studies with SDK, but none regarding fentanyl and ketamine. In one study, combination SDK and reduced dose hydromorphone produced rapid pain relief without significant side effects. Another study indicated that morphine and SDK both provided adequate pain relief alone, but combined morphine and SDK required less morphine administration, had faster onset of relief, and provided sustained reduction in pain intensity for up to 2 hours.

Conditions

Pain, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Sub-Dissociative Ketamine alone

0.3 mg/kg of Sub-Dissociative Ketamine IV administered over at least 1 minute

Group Type: ACTIVE_COMPARATOR

Ketamine

Intervention Type: DRUG

0.3 mg/kg of Sub-Dissociative Ketamine IV administered over at least 1 minute

Fentanyl alone

1 mg/kg of Fentanyl IV administered over at least 1 minute

Group Type: ACTIVE_COMPARATOR

Fentanyl

Intervention Type: DRUG

1 mg/kg of Fentanyl IV administered over at least 1 minute

Sub-dissociative Ketamine and Fentanyl

Combined dose of 0.15 mg/kg of Sub-dissociative Ketamine and 0.5 mg/kg of Fentanyl IV administered over at least 1 minute

Group Type: EXPERIMENTAL

Fentanyl and Ketamine

Intervention Type: COMBINATION_PRODUCT

Combined dose of 0.15 mg/kg of Sub-dissociative Ketamine and 0.5 mg/kg of Fentanyl IV administered over at least 1 minute.

Interventions

Fentanyl

1 mg/kg of Fentanyl IV administered over at least 1 minute

Intervention Type: DRUG

Fentanyl and Ketamine

Combined dose of 0.15 mg/kg of Sub-dissociative Ketamine and 0.5 mg/kg of Fentanyl IV administered over at least 1 minute.

Intervention Type: COMBINATION_PRODUCT

Ketamine

0.3 mg/kg of Sub-Dissociative Ketamine IV administered over at least 1 minute

Intervention Type: DRUG

Other Intervention Names

Fentanyl Citrate; Ketamine Hydrochloride

Eligibility Criteria

Inclusion Criteria

• 18 - 65 years old
• Moderate pain defined as 4-6 out of 10, severe pain defined as ≥ 7 out of 10 as defined by the numeric rating pain scale (NRS)
• Proficient in reading and understanding English
• Are deemed by the attending physician to require opioid therapy.

Exclusion Criteria

• Inability to give consent,
• Inability to use the numeric rating scale (NRS) score
• Long-term use of opioids, history of chronic pain
• Known substance abuse known as excessive use of a drug such as (e.g. alcohol, narcotics or cocaine)
• Known hypersensitivity to ketamine or fentanyl
• Pregnancy
• Alcohol intoxication
• Depression
• Anxiety
• Chronic obstructive pulmonary disease
• Asthma
• Cirrhosis
• On dialysis
• Acute ischemic stroke
• Heart rate (HR) less < 60 bpm or > 120 bpm
• Systolic blood pressure (SBP) < 90 mmHg or > 180 mmHg
• Ischemic heart disease
• Ketamine prior to arrival
• Trauma patients
• Sepsis or septic shock
• Weight > 100 kg.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mercy Health Ohio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Gemmel

Role: STUDY_DIRECTOR

Director of Research

Locations

St. Elizabeth Boardman Hospital

Boardman, Ohio, United States

Countries

United States

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Related Links

https://www.accessdata.fda.gov/scripts/drugshortages/

U.S. Department of Health and Human Services. (2018, October 15). U.S. Food and Drug Administration. Retrieved October 15, 2018, from https://www.accessdata.fda.gov/scripts/drugshortages/

Other Identifiers

18-040

Identifier Type: -

Identifier Source: org_study_id