Low Dose Ketamine (LDK) Versus Morphine for Acute Pain Control in the Emergency Department

• ClinicalTrials.gov Identifier: NCT01538745
• Recruitment Status: Completed
• First Posted: February 24, 2012
• Results First Posted: February 4, 2021
• Last Update Posted: February 4, 2021
• Sponsor: Brooke Army Medical Center
• Collaborator: U.S. Air Force Office of the Surgeon General
• Information provided by (Responsible Party): Joshua Miller, Brooke Army Medical Center

Tracking Information

• First Submitted Date: February 21, 2012
• First Posted Date: February 24, 2012
• Results First Submitted Date: July 17, 2013
• Results First Posted Date: February 4, 2021
• Last Update Posted Date: February 4, 2021
• Study Start Date: February 2012
• Actual Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2021)

Maximal Change in Numerical Rating Scale (NRS) Pain Score From Baseline NRS Pain Score [ Time Frame: 5,10,20,40,60,80,100,120 minutes post dose ]

Numerical Rating Scale (NRS) pain score is an 11-point rating scale for pain. With 0 being no pain and 10 being the worst pain imaginable.

Original Primary Outcome Measures (submitted: February 21, 2012)

Maximal change in NRS pain score as a percentage of initial NRS pain score [ Time Frame: 20,40,60,80,100,120 minutes post dose ]

Evaluation of the maximal change in patient's pain (based on their numerical rating scale score) throughout the study versus their initial pain rating prior to drug administration.

Current Secondary Outcome Measures (submitted: February 3, 2021)

• Time to Change in NRS Pain Score [ Time Frame: 5,10, 20,40,60,80,100,120 minutes ]
  Following dosage with study medication, the amount of time taken to demonstrate a change in the patient's NRS pain score. Time to Change in NRS Pain Score for the Reporting Group as a whole will be made
• Time to Maximal Change in NRS Pain Score [ Time Frame: 5, 10, 20 minutes and then every 20 minutes to a total of 120 minutes ]
  Following dosage with study medication, the interval time taken to demonstrate the maximal change in the patient's NRS pain score will be reported for each group.
• Incidence of Treatment Failure [ Time Frame: 120 minutes ]
  Requiring more than two doses of the study medication provided for adequate pain control
• Incidence of Side Effects, Including Outlying Vital Signs [ Time Frame: 5,10,20,40,60,80,100,120 minutes ]
  The patient will be assessed for vital signs (blood pressure, heart rate, respiratory rate, oxygen saturation), and all side effects at 5,10,20 minutes following medication administration and then every 20 minutes until a total of 120 minutes from the first dose of study medication. All side effects and outlying vital signs will be documented.
• Maximum Deviation From 0 on the Richmond Agitation Sedation Scale (RASS) [ Time Frame: 5,10,20,40,60,80,100,120 minutes ]
  Using 0 as the "normal/baseline" on the RASS, maximal deviation in either direction will be used to demonstrate the effect of the study medications on levels of sedation or agitation. Results will be reported as Richmond Agitation Sedation Scale (RASS) scores range from:

  • 4 Combative: Overtly combative, violent, immediate danger to staff
  • 3 Very agitated: Pulls or removes tube(s) or catheter(s); aggressive
  • 2 Agitated: Frequent non-purposeful movement
  • 1 Restless: Anxious but movements not aggressive. vigorous 0 Alert and calm
    • 1 Drowsy: Not fully alert, but has sustained awakening (eye-opening/eye contact) to voice (>10 seconds)
    • 2 Light sedation: Briefly awakens with eye contact to voice (<10 seconds)
    • 3 Moderate sedation: Movement or eye opening to voice (but no eye contact)
    • 4 Deep sedation: No response to voice, but movement or eye opening to physical stimulation
    • 5 Unarousable: No response to voice or physical stimulation

Original Secondary Outcome Measures (submitted: February 21, 2012)

• Time to change in NRS pain score [ Time Frame: 20,40,60,80,100,120 minutes ]
  Following doseage with study medication, the amount of time in increments of 20 minutes taken to demonstrate a change in the patient's NRS pain score.
• Time to maximal change in NRS pain score [ Time Frame: every 20 minutes to a total of 120 minutes ]
  Following doseage with study medication, the amount of time in increments of 20 minutes taken to demonstrate the maximal change in the patient's NRS pain score.
• Duration of maximal change in NRS pain score [ Time Frame: 20,40,60,80,100,120 minutes ]
  Maximal change in NRS pain score is to be defined as the largest change from patient's baseline pain score. Duration of maximal change is how long the patient's pain score remained at this level.
• Incidence of treatment failure [ Time Frame: 120 minutes ]
  Requiring more than two doses of the study medication provided for adequate pain control
• Incidence of side effects, including outlying vital signs [ Time Frame: 20,40,60,80,100,120 minutes ]
  The patient will be assessed for vital signs (blood pressure, heart rate, respiratory rate, oxygen saturation), Numerical Rating Score (NRS) and Richmond Agitation Sedation Scale (RASS) score at 5,10,20 minutes following medication adminstration and then every 20 minutes until a total of 120 minutes from the first dose of study medication. All side effects and outlying vital signs will be documented.
• Maximum deviation from 0 on the Richmond Agitation Sedation Scale (RASS) [ Time Frame: 20,40,60,80,100,120 minutes ]
  Using 0 as the "normal/baseline" on the RASS, maximal deviation in either direction will be used to demonstrate the effect of the study medications on levels of sedation or agitation.
• Nurse and physician satisfaction scores [ Time Frame: 120 minutes after start of study ]
  The patient's treating nurses and physicians/PAs will be given a survey to evaluate the level of pain control they believe the patient acheived.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Low Dose Ketamine (LDK) Versus Morphine for Acute Pain Control in the Emergency Department
• Official Title: Low Dose Ketamine (LDK) Versus Morphine for Acute Pain Control in the Emergency Department

Brief Summary

The purpose of this study is to compare the safety and effectiveness of intravenous low dose ketamine (LDK) to the industry standard of morphine (MOR) in regards to controlling acute pain in the emergency department.

Both LDK and morphine have side effects. The amount and character of these side effects will be compared. Additionally, the degree of sedation or agitation will be specifically measured. The aim of this current study is to make this comparison and shift the evidence for LDK use from the anecdotal to the scientific.

Detailed Description

Phase 1 is a randomized, controlled, double-blinded study comparing the use of low-dose ketamine (LDK) to morphine for acute pain control in emergency department patients. A convenience sample of subjects will be enrolled from a population of patients aged 18-50 who present to the Brooke Army Medical Center Emergency Department with acute abdominal pain, flank/lumbar back pain and/or pain to the extremities. To take part in the study, a need for opioid analgesia must be indicated by the treating physician in addition to the patient meeting all other study criteria.

The patient will then be randomized into one of the two treatment arms. Prior to receiving either the study medication (ketamine) or the active control (morphine) the patient will be asked to rate their pain on a numeric rating scale (NRS) with 0 being no pain and 10 being the worst pain possible. Their baseline vital signs (blood pressure, heart rate, respiratory rate and oxygen saturation) will also be documented. These vital signs and the NRS will be reassessed at 5, 10 and 20 minutes post medication dosage. At 20 minutes they will also document a Richmond Agitation Sedation Scale (RASS) score and will ask the patient if they require additional pain medication. If the patient denies the need for a second dose of medication they will continue to be re-assessed every 20 minutes (vital signs, NRS, and RASS) until either inpatient admission, discharge home, transfer to the operating room or until a total of 120 minutes after initial dosing.

If at any time during the study the patient requires a second dose of pain medication, following the administration of the med, they will be assessed for vital signs at 5,10 and 20 minutes after the dose. At 20 minutes, a RASS score and NRS score will also be documented. They will then be re-assessed every 20 minutes (vital signs, NRS, and RASS) until either inpatient admission, discharge home, transfer to the operating room or until a total of 120 minutes after initial dosing.

If they require a third dose of pain medication at any time during the study, this is considered a treatment failure and the treating physician will be contacted to provide any further pain control.

The second phase of the study will be observational. An anonymous satisfaction survey will be provided to the treating nurse, physician or physicians assistant (PA) of the patients recruited from part one of the study. The purpose of conducting the survey is so that an observation point of view can be added to the data to provide a measure of how well the patient's pain was controlled.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment

Condition

• Abdomen, Acute
• Other Acute Pain
• Flank Pain
• Back Pain
• Musculoskeletal Pain

Intervention

• Drug: Ketamine
  0.3 mg/kg ketamine Intravenous push (IVP) over 5 minutes. Total of two possible doses.
  Other Name: Ketalar
• Drug: Morphine
  0.1 mg/kg Morphine IVP over 5 minutes. Total of two possible doses.
  Other Names:

  • MS Contin
  • Roxanol
  • Kadian
  • Avinza

Study Arms

• Experimental: Ketamine
  0.3 MG/KG IV KETAMINE ADMINISTERED OVER 5 MINUTES. MAX DOSE OF 25MG.
  Intervention: Drug: Ketamine
• Active Comparator: Morphine
  0.1 MG/KG IV MORPHINE ADMINSITERED OVER 5 MINUTES. MAX DOSE 8MG.
  Intervention: Drug: Morphine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 3, 2021): 45
• Original Estimated Enrollment (submitted: February 21, 2012): 210
• Actual Study Completion Date: June 2013
• Actual Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients age 18-59 who present to the Brooke Army Medical Center Emergency Department with acute (less than 10 days) abdominal pain, flank/lumbar back pain and or/pain to the extremities, and of sufficient severity in the judgement of the ED treating physician or PA to warrant use of intravenous opioids

Exclusion Criteria:

• Poor vital sign stability hypoxia: Sats<95% hypotension: SBP<90 hypertension: SBP>180 heart rate: <50 or >120 respiratory rate: <10 or >30
• Altered mental status or intoxication
• Patient is unwilling to participate or provide informed consent
• History of chronic pain or pain syndrome with concurrent opioid medication use
• fibromyalgia
• Patient has received opioids and/or tramadol in the past 4 hours
• Prescription pain medication use (to exclude muscle relaxants, acetaminophen or NSAIDs including toradol) in the past 4 hours
• Allergy to morphine or ketamine
• Sole provider status
• Adverse reaction to morphine or ketamine in the past
• Patients, who in the opinion of the triage nurse, require immediate analgesic relief
• Patient is female of child-bearing age and unable to provide urine or serum for HCG analysis in triage
• Pregnancy or breast feeding
• Presence of oxygen dependent pulmonary disease, liver cirrhosis or Renal disease requiring dialysis. (as assessed by electronic chart review)
• Presence of Ischemic heart disease, heart failure or unstable dysrhythmias (as assessed by electronic chart review)
• Presence of intracranial mass or vascular lesion.
• Presence of psychosis or hallucinations
• Weight greater than 115kg or less than 45 kg
• History of acute ocular/head trauma
• History of increased intracranial pressure/hypertensive hydrocephalus
• Non-English speaking patients

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 59 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01538745
• Other Study ID Numbers: C.2011.173
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Joshua Miller, Brooke Army Medical Center
• Original Responsible Party: Joshua Miller, Brooke Army Medical Center, Joshua Miller, Capt, USAF, MC
• Current Study Sponsor: Brooke Army Medical Center
• Original Study Sponsor: Same as current
• Collaborators: U.S. Air Force Office of the Surgeon General

Investigators

• Principal Investigator: Joshua P Miller, MD; United States Air Force

• PRS Account: Brooke Army Medical Center
• Verification Date: February 2021