Clinical trial NCT02489630: Low Dose Ketamine as an Adjunct to Opiates for Acute Pain in the Emergency Department
Official title: Low Dose Ketamine as an Adjunct to Opiates for Acute Pain in the Emergency Department
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Pain
Pain
Lead sponsor: Carilion Clinic
Sponsor class: OTHER
Collaborators: name: Virginia Polytechnic Institute and State University
name: University of Memphis
First posted: 2015-07-03
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study investigates the use of low doses of ketamine, along with opiate pain medication, is more effective at controlling the acute pain of patients in the emergency department than opiate pain medication alone. In addition, this study examines whether patients treated with low doses of ketamine, along with opiate pain medication, will require less opiate pain medication to control their pain, and whether these patients are equally happy with their pain control as patients who receive only opiate pain medication.

Detailed description: This randomized, double blinded, placebo controlled study investigates the use of low-dose ketamine, in conjunction to standard opiate treatment, as compared to placebo plus standard opiate treatment, for acute painful conditions in the ED setting. The investigators hypothesize that patients treated with ketamine will require less opiate for similar levels of pain relief up to 2 hours from initiation of treatment, with similar levels of patient satisfaction and an acceptable side effect profile.

Once seen by a physician, potential patients will receive provider-determined opiate treatment for their painful condition, prior to the informed consent process to ensure that treatment is not delayed. Once identified for inclusion, patients will receive informed consent and, upon consent, will subsequently be randomized through block randomization into one of two study groups. Each study group will contain at least 50 subjects. Randomization will be determined using a table of random numbers, using a restricted randomization scheme to ensure roughly equal numbers in each group. Group assignments will be sealed in opaque envelopes to be opened sequentially by the investigators. Group assignments will not indicate whether it is the treatment or the control group. At this time (T0), an initial NRS-11 score will be obtained. The NRS-11 is an 11-point scale on which patients rate their level of pain from 0 ("no pain") to 10 ("worst pain imaginable"). If, after initial analgesic, pain level is \<6, patients will be asked again in 15 min. If at this time it is still \<6, they will not proceed in the study. The intervention group will receive 0.1 mg/kg of ketamine given over 1 minute, and the control group will receive an equivalent volume of normal saline; both groups will have received a provider-determined dose of opiate analgesia prior to enrollment. At thirty-minute intervals, subjects will be asked their level of pain, if they need more pain control and will be evaluated for the presence of side effects (hallucinations, dysphoria, weakness, diplopia, nausea, vomiting, dizziness, itching and bradypnea) as well as sedation as defined by Ramsay score of greater than 2. Repeat doses of pain medication will be given as 0.05 mg/kg morphine or equivalent dose of opioid analgesic. Total opiate dosage and number of repeat doses given at the end of 120 minutes will be recorded. At each time interval, as well as at the end of 120 minutes (T120), patient satisfaction with pain control will be recoded on the 4-point Likert scale, with 0 being "completely unsatisfied" and 3 being "very satisfied".

Eligibility criteria: Inclusion Criteria:

* Greater than 18 years but less than 70 years old.
* Exhibiting pain defined on a numerical rating scale (NRS-11 \[Farrar et al. 2001\]) score of equal to or greater than 6 out of 10
* Deemed by the treating EM physician to require opioid analgesia.

Exclusion Criteria:

* Respiratory, hemodynamic or neurologic compromise, as determined by observation of signs of respiratory distress, systolic blood pressure less than 90 mmHg or systolic/diastolic blood pressure greater than 160/90, or a Glasgow -Coma Score less than 15.
* A history of chronic ventilation, dialysis or with previously diagnosed cirrhosis or hepatitis by istory.
* Active psychosis.
* Clinical intoxication.
* Known sensitivity to any study drug.
* An inability to understand the NRS-11 pain measurement scale.
* Presentation with headache or chest pain.
* Pregnancy.
* A lack of decision-making capacity.
* A pain score less than 6 on the NRS-11 scale.
* A concern by the treating physician or study personnel of current or prior history of narcotic abuse, or other secondary gain.
* Previously participated in the study.

Primary outcomes:
measure: Change in Level of Pain Control as Reported on the NRS-11
timeFrame: 20 min pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
measure: Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale
timeFrame: 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Secondary outcomes:
measure: Difference in Opiate Dosage Between Study Arms in Morphine Equivalents
timeFrame: 20 mins pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Other outcomes:
Locations:
Study officials:
affiliation: Physician
name: Corey R Heitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ahern TL, Herring AA, Stone MB, Frazee BW. Effective analgesia with low-dose ketamine and reduced dose hydromorphone in ED patients with severe pain. Am J Emerg Med. 2013 May;31(5):847-51. doi: 10.1016/j.ajem.2013.02.008. Epub 2013 Apr 18.
citation: Beaudoin FL, Lin C, Guan W, Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Acad Emerg Med. 2014 Nov;21(11):1193-202. doi: 10.1111/acem.12510.
citation: Galinski M, Dolveck F, Combes X, Limoges V, Smail N, Pommier V, Templier F, Catineau J, Lapostolle F, Adnet F. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. Am J Emerg Med. 2007 May;25(4):385-90. doi: 10.1016/j.ajem.2006.11.016.
citation: Jennings PA, Cameron P, Bernard S, Walker T, Jolley D, Fitzgerald M, Masci K. Morphine and ketamine is superior to morphine alone for out-of-hospital trauma analgesia: a randomized controlled trial. Ann Emerg Med. 2012 Jun;59(6):497-503. doi: 10.1016/j.annemergmed.2011.11.012. Epub 2012 Jan 13.
citation: Johansson P, Kongstad P, Johansson A. The effect of combined treatment with morphine sulphate and low-dose ketamine in a prehospital setting. Scand J Trauma Resusc Emerg Med. 2009 Nov 27;17:61. doi: 10.1186/1757-7241-17-61.
citation: Kissin I, Bright CA, Bradley EL Jr. The effect of ketamine on opioid-induced acute tolerance: can it explain reduction of opioid consumption with ketamine-opioid analgesic combinations? Anesth Analg. 2000 Dec;91(6):1483-8. doi: 10.1097/00000539-200012000-00035.