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Comparing Ketamine and Morphine in the Treatment of Acute Fracture Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02430818
Recruitment Status : Terminated (were not able to enroll patients to a satisfactory level)
First Posted : April 30, 2015
Results First Posted : May 22, 2019
Last Update Posted : May 22, 2019
Sponsor:
Collaborator:
MOCEP
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE April 25, 2015
First Posted Date  ICMJE April 30, 2015
Results First Submitted Date  ICMJE July 3, 2018
Results First Posted Date  ICMJE May 22, 2019
Last Update Posted Date May 22, 2019
Study Start Date  ICMJE April 2015
Actual Primary Completion Date September 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2019)
Pain Treatment-VAS (Visual Analog Scale) [ Time Frame: At 0 minutes and 60 minutes ]
Study outcomes involve change in participants' pain as measured by a visual analog scale. The scale is a 10 inch line from 0 to 10 inches with 10 being the most pain and 0 being no pain. There are no units on the scale; it is just a straight line from no pain (0) to the worst pain (10). We assessed at o, 15, and 60 minutes but only scored the VAS at 60 minutes.
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2015)
Pain Treatment (visual analog scale) [ Time Frame: 60 minutes ]
Study outcomes involve change in participants' pain as measured by a visual analog scale
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2019)
  • Number of Participants With an Adverse Effects [ Time Frame: 60 minutes ]
    We will monitor for adverse effects and record for changes in vital signs including nausea and vomiting, hypotension, respiratory depression, laryngospasm, and emotional and psychological effects (emergence reactions).
  • Would the Participant Would Consider Using the Drug Given to Them for Pain Relief in the Future [ Time Frame: 60 minutes ]
    Patients will be assessed to determine whether the participant would consider using the drug given to them for pain relief in the future. It was measured on a likert scale from 1-5 with 1 being did not like and would not use the drug again to 5 being like and would definitely receive the medication again. There are no units. The numbers below are the total number of patients that completed this answer. This was only asked on patients that received medication as if they did not receive medication the answer would not make sense. The median value is the likert value on a scale of 1-5 with the standard deviation.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2015)
  • Adverse Effects [ Time Frame: 60 minutes ]
    We will monitor and record for changes in vital signs including hypotension, hypertension, tachycardia, bradycardia, respiratory depression. We will also monitor for nausea and vomiting, laryngospasm, and emotional and psychological effects (emergence reactions).
  • Patient satisfaction (whether the participant would consider using the drug given to them for pain relief in the future) [ Time Frame: 60 minutes ]
    Patients will be assessed to determine whether the participant would consider using the drug given to them for pain relief in the future.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparing Ketamine and Morphine in the Treatment of Acute Fracture Pain
Official Title  ICMJE Comparing the Effectiveness of Low-dose Ketamine With Morphine to Treat Pain in Patients With Long Bone Fractures
Brief Summary Opioid pain medications such as morphine and dilaudid are commonly used in emergency departments to treat pain in patients. Physicians are familiar with the side effects of these medications; the most concerning of which is slowing or stopping a patient's breathing, as well as dangerously lowering their blood pressure. An alternative medication is ketamine. This medication is also commonly used in the emergency department, although it is typically used to help sedate patients for uncomfortable procedures. Ketamine has also been used for pain control, but in a much lower dosage that does not sedate patients. When used for analgesia, it has typically been administered in combination with opioid pain medications. To date, there is no study that looks at the effectiveness and safety of using a low dose ketamine alone in comparison to the use of morphine. The purpose of this study is to measure how well low-dose ketamine treats pain compared to morphine and to look at how often serious side effects are seen with each medication.
Detailed Description

Opioid analgesia is the standard of care for treating moderate to severe pain in the emergency department. It is an effective medication that most practitioners are familiar using. Opioid use is not without risk, however. In managing acute pain, patients may experience hypotension, respiratory depression, hypoxia, nausea and vomiting, dysphoria, and itching. Patients at risk for respiratory depression include those with advanced age, renal failure, or treated with multiple other sedatives.

The current recommended dose for opioid administration for acute pain management is approximately 0.1 mg/kg as a loading dose, although some sources recommend up to 10 mg for patients weighing more than 50 kg. (Ducharme 2011; Yak 2011) A single center study demonstrated that patients received an average of 0.08 mg/kg of morphine, which did not adequately control their pain; no patient received an initial dose of 10 mg.(Bijur 2012) A post-operative pain study demonstrated that patients needed on average 12 mg or a mean weight-based dose of 0.17 mg/kg of morphine to achieve an acceptable level of pain reduction as determined by a 30 mm change on a visual analog scale.(Aubrun 2003) As such even if patients received 1 mg of hydromorphone, their pain would still not be adequately controlled.

Ketamine is a dissociative anesthetic that is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors. Low dose ketamine (LDK) (0.03-0.05 mg/kg) has analgesic properties by modulating opioid tolerance and hyperalgesia.(Uprety 2013) Currently, ketamine is used in the emergency department for moderate sedations and "awake" intubations. In the pre-hospital setting, it is used in the management of patients with excited delirium and pain control.(Keseg 2014)(Wiel 2014)(Jennings 2013) Benefits include fewer serious adverse effects, especially involving respiratory depression and hypotension which occurs with high-dose or repeat doses of opioids.(Jennings 2013) In addition to not causing hypotension, ketamine can elevate a patient's blood pressure, which may be useful in some circumstances.(Johansson 2009) Emergence delirium is associated with ketamine; this is a rare adverse event and is usually alleviated with benzodiazepines. Additionally, LDK is unlikely to cause the emergence delirium or the dissociation usually associated with larger doses. Another potential complication is laryngospasm. Fortunately, this too is rare and in most cases, patients are easily bagged through the event.

LDK is efficacious in reducing multiple types of pain in a variety of settings. Ketamine infusions can reduce pain from vaso-occlusive pain crises seen in patients with sickle cell anemia.(Uprety 2013)(Neri 2013)(Jennings 2013) In the postoperative setting and intensive care unit, ketamine reduced the amount of morphine required to control pain.(Galinski 2007)(Bell 2006)(Herring 2013) In out-of-hospital trauma patients, ketamine combined with morphine produced superior analgesia to morphine alone. All patients received morphine and were then randomized to receive either morphine or ketamine if further analgesia was required. Ketamine had a change in the visual analog scale (VAS) of -5.6 (CI -6.2 to -5.0) while morphine had had a change of -3.2 (CI -3.7 to -2.7).(Jennings 2012) In another pre-hospital study, ketamine was administered to 1030 patients for pain or anesthesia. No patients incurred ketamine-induced respiratory adverse events.(Bredmose 2009) Preliminary studies have also investigated LDK in the emergency department (ED). Available research mainly consists of retrospective or observational data. In an observational study performed in an urban ED in California, LDK significantly improved patient's pain without adversely effecting blood pressure, heart rate, or respiratory drive. Twenty-four patients over age 18 who received ketamine for any reason were included. Three received ketamine for sedation while the rest received it for analgesia. Most patients received opioids prior to receiving ketamine, although the opioids did not result in improved pain scores. On a scale of 0 to 10, ketamine reduced pain from 8.9 ± 2.1 to 3.9 ± 3.4 (p<0.0001).(Richards 2013) In another observational, ED based study, ketamine used as an analgesic was investigated. Thirty patients with a variety of painful complaints (abdominal pain, back pain, nephrolithiasis, biliary pain, fractures, sickle cell pain) were enrolled. Patients were initially administered a combination of hydromorphone 0.5 mg and ketamine 15 mg with rescue doses of hydromorphone 1 mg available 15 minutes and 30 minutes after the initial dose of analgesia. In 28 patients (93%), there was a clinically significant decrease of 2 or more points on a numerical rating score measured after the initial administration; 14 patients reported pain scores of 0. Fourteen patients refused any additional hydromorphone and 24 patients (80%) either refused additional hydromorphone at 15 minutes or received a dose at 15 minutes but declined a dose at 30 minutes. Dizziness, nausea, headache, and some dissociative effects were reported.(Ahern 2013) Ketamine administered for analgesia in an urban trauma center was retrospectively reviewed in 35 patients. The most common chief complaint was abscess (46%). The median dose of ketamine received was 10 mg (range 5-35 mg); opioids were co-administered in almost all cases (91%). LDK improved pain scores by at least 3 points in 19/35 patients (54%). Eight patients did not receive a post-drug administration pain score.(Lester 2010) A convenience sample of patients was enrolled in an ED based study in British Columbia. Any patients older than 6 years of age presenting with a painful condition were eligible for enrollment. Patients had to have a score of at least 50 on a 100-mm visual analog score (VAS). All patients received 0.5 mg/kg of intranasal (IN) ketamine and could receive a rescue dose of 0.25 mg/kg IN after 10 minutes for VAS > 50. Within 30 minutes, 35 patients (88%) had a decrease in VAS of at least 13 mm. Patient reported satisfaction was a mean of 7 (5-9) on a patient satisfaction scale of 1-10. Dizziness, nausea, and fatigue were all reported.(Andolfatto 2013) IN ketamine was also demonstrated as an effective analgesic in other pediatric and adult ED based studies.(Yeaman 2013)(Yeaman 2014) While ketamine has been studied in the ED, the available research has multiple limitations. Most of it consists of observational or retrospective studies. As such, there could be multiple explanations for their results due to multiple, uncontrolled confounders. In addition, most studies included patients with any painful complaint and did not have a comparison or control group. We plan to conduct a prospective, randomized study of ketamine compared to opioids in long bone fractures.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Pain
  • Fractures
Intervention  ICMJE
  • Drug: ketamine
  • Drug: morphine
Study Arms  ICMJE
  • Experimental: Ketamine
    Ketamine is a dissociative agent that is thought to modulate pain by binding to NMDA receptors. Participants assigned to the ketamine arm will be given 0.4 mg/kg IV of ketamine (40 mg maximum).
    Intervention: Drug: ketamine
  • Experimental: Morphine
    Morphine is an opioid that acts on opioidergic receptors to modulate pain. Participants in the opioid arm will receive 0.1 mg/kg IV of morphine (10 mg maximum).
    Intervention: Drug: morphine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 30, 2019)
13
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2015)
40
Actual Study Completion Date  ICMJE September 2017
Actual Primary Completion Date September 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Eligible Long bone fractures. This will include:
  • Humerus
  • Tibia
  • Fibula
  • Femur
  • Radius
  • Ulna

Exclusion Criteria:

  • Injuries older than 24 hours
  • Avulsion fractures
  • History of substance abuse
  • History of chronic opioid dependence
  • Pregnancy
  • Demonstrates signs of intoxication
  • Allergic to ketamine or opioids
  • Patients unable to consent
  • Hemodynamically unstable (SBP >180mmHg or <100mgHg, HR >130bpm, Respiratory rate <10, oxygen saturations <90%
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02430818
Other Study ID Numbers  ICMJE 201501068
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Washington University School of Medicine
Original Responsible Party Evan Schwarz, Washington University School of Medicine, Assistant Professor
Current Study Sponsor  ICMJE Washington University School of Medicine
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE MOCEP
Investigators  ICMJE
Principal Investigator: Nicholas Musisca, MD Physician
PRS Account Washington University School of Medicine
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP