Clinical trial NCT03714620
Conditions: Acute Pain
Sponsor: Loyola University
Start date: 2018-10-15; Completion date: 2019-09-17
Enrollment: 98 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Goal is to determine if in adults presenting to the Emergency Department (ED) with moderate to severe acute pain, Ketamine administered at 0.15 mg/kg will provide similar pain relief to Ketamine administered at 0.3 mg/kg, with fewer adverse effects.

Detailed description:
Study investigators will enroll participants who present to the Emergency Department (ED) with moderate to severe acute pain, and require intravenous pain medication. Participants will be double-blinded and randomized to one of the two treatment groups.

Investigators aim to determine if ketamine 0.15 mg/kg IVPB is non-inferior to ketamine 0.3 mg/kg IVBP for the treatment of acute moderate to severe pain in the Emergency Department (ED). Study investigators hypothesize that in adults presenting to the ED with moderate to severe acute pain, SDK administered at 0.15 mg/kg will provide similar pain relief to SDK at 0.3 mg/kg, with reduced adverse effects.

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Ketamine
Intervention descriptions: intervention 1: Ketamine 0.15 mg/kg vs. 0.3 mg/kg IVPB over 15 minutes

Protocol documents:
Prot_SAP_000.pdf: 
 
Sub-dissociative Dose Ketamine Dosing Study 
 
NCT03714620 
 
Date 10/17/2018 
 
 


I. 
Study Protocol 
 
Patient screening, enrollment, and data collection will be performed by the study investigators. 
All adults >18 years of age and < 60 years of age and weighing between 45-115 kg with acute 
abdominal, flank, back, musculoskeletal pain, or headache, with a score of 5 or more on a 
standard 11-point (0 to 10) VAS pain rating scale requiring intravenous analgesia, as determined 
by the treating attending physician, will be screened for inclusion. Exclusion criteria are as 
follows: pregnancy, breast-feeding, altered mental status rendering the patient unable to 
consent to the study, allergy to ketamine, unstable vital signs (systolic blood pressure <90 
or >180 mm Hg, pulse rate <50 or >150 beats/minute, and respiration rate <10 or >30 
breaths/minute), and medical history of acute head or eye injury, seizure, intracranial 
hypertension, chronic pain, renal or hepatic insufficiency, history of alcohol or drug abuse, and 
psychiatric illness. Only the first admission will be included if patients present multiple times 
during the study period. 
 
 
i. Recruitment procedures 
1. Where will recruitment occur? 
Recruitment will occur in the LUMC ED upon patient’s arrival and once physician has deemed it 
necessary that the patient receive intravenous pain medication. 
2. Where and when will consent be obtained? 
Consent will be obtained in the Emergency Department once it is determined that the patient 
meets inclusions criteria for enrollment if the patient is able to provide it.  
3. Who will obtain consent? 
The treating attending physician, or one of physician members of the research team, will obtain 
consent from the patient in the ED.  
ii. Screening procedures 
Patients will be screened as a convenience sample during daytime hours Monday – Friday when 
any of the study investigators are working and the ED clinical pharmacist is available to prepare 
the study drug and randomize the patients. Patients presenting to the ED with acute moderate 
to severe abdominal, flank, back, musculoskeletal pain, or a headache will be screened for 
inclusion criteria and asked to consent prior to enrollment. Consent must be obtained prior to 
enrollment.  
b. Randomization procedures (if applicable) 
The study will be double-blinded and randomized. Patients meeting inclusion criteria who 
consent for participation will be randomized in a 1:1 fashion to either Ketamine 0.15 mg/kg 
IVBP or Ketamine 0.3 mg/kg IVBP. Dosing will be based on actual body weight. Both drugs will 
be administered over 15 minutes. Physicians will obtain consent from the patient, but will not 
be aware of dose that the patient receives. Treatment will be prepared and blinded by the ED 
clinical pharmacist. ED Pharmacist will maintain the randomization list, which was generated 
before commencement of the study, prepare the medication, and deliver it to the nurse caring 
for the study participant in a blinded manner.  
 
c. Study Intervention 


i. For Drug/device studies: 
1. Active study agents 
Ketamine 0.15 mg/kg IVBP administered over 15 minutes 
Ketamine 0.3 mg/kg IVBP administered over 15 minutes 
2. Placebo study agents 
No placebo 
3. Blinding/labeling/preparation of agents 
Patients will be randomized in a 1:1 fashion to receive either 0.15 mg/kg of Ketamine IVPB or 
0.3 mg/kg of Ketamine IVBP.  The ED clinical pharmacist will prepare and label the study 
treatments, and ensure blinding of the patient, research team, and clinical staff.  
4. Storage 
Storage of the study medication will be kept in the ED pyxis to facilitate rapid use.  
5. Administration 
0.15 mg/kg or 0.3 mg/kg dose of Ketamine administered intravenously over 15 minutes 
6. Toxicities and guidelines for adjustments 
No dosage adjustment will be necessary.  
ii. For Other types of intervention studies: n/a 
1. Active intervention description 
2. Control group 
 
d. Study Assessments and Activities 
i. Describe all study procedures, assessments, and subject activities 
Patients will be consented for participation by one of the study investigators or the treating ED 
attending physician. The ED pharmacist will prepare the medication, and ensure blinding of the 
patient, research team, and clinical staff. The nurse caring the patient will administer the IV 
medication and give the patient a survey to fill out regarding pain relief and side effects at 15 
minutes, 30 minutes, and 60 minutes post initiation of administration of the ketamine. Time 
zero will be time the drug administration is initiated. The survey will ask the patient to rate their 
pain using the VAS pain rating scale. Additionally, it will have a list of adverse effects, and the 
patient will need to rate each adverse effect using a 5 point SERSDA scale (rating each adverse 
event from “absent” to “very bothersome”). At the same time intervals (15, 30, and 60 minutes 
post initiation of drug administration), the nurse will rate the patient using the RASS scale. Vital 
signs will be monitored per ED protocol. Rescue analgesia will be offered at 30 minutes.  
ii. Provide a schedule of all study assessments and subject activities, 
including a tabular representation or timeline as applicable 
-Patient presents to the emergency department with acute pain 
-Emergency treatment will not be delayed for the purposes of this study 
-Patient seen by physician and screened for inclusion/exclusion criteria 
-Patient consented for participation by research team member or physician treating the 
patient  
-Patient randomly assigned to treatment group 
-Drug prepared by ED pharmacist, administered by blinded nurse 
-Time zero (0) is when nurse initiates administration of the ketamine 
-Ketamine infuses over 15 minutes, ending at 15 min time mark 


-Survey administered to the patient to be filled out at 15 min, 30 min and 60 min post 
administration of the ketamine (nurse to alert patient at specified time intervals) 
-Nurse to score patient using RASS scale at 15 min, 30 min, 60 min post initiation of  
drug administration  
 
II. 
Safety Monitoring Plan 
a. Definition of adverse events, serious adverse events 
Adverse effects include dizziness, disorientation, dysphoria, nausea. Adverse events include 
hypoxia (<90%), hypotension (<90 systolic), vomiting, or life-threatening events. 
b. What procedures will be used to monitor subject safety?   
Ketamine is currently being used in sub-dissociative doses in the ED at LUMC to treat acute pain 
utilizing doses between 0.1 mg/kg- 0.3 mg/kg. The procedures to monitor safety are consistent 
with the ED guidelines used in current practice at LUMC. Subjects will have continuous 
telemetry monitoring including heart rate, respiratory rate and oxygen saturation.  Vital signs 
(including but not limited to blood pressure measurements) will be measured and documented 
per standard protocol in the ED. Documented adverse side effects of sub-dissociative ketamine 
have included dizziness, dysphoria, and disorientation, but no serious adverse events have been 
noted. 
c. Who (list names) will identify, document, and report adverse events? 
The blinded physician, nurse caring for patient, or one of the research team members, will 
identify, document, and report adverse events. 
d. What is the frequency for review of summarized safety information and who will 
perform the review (e.g., safety monitoring board)? 
The research team will review safety information weekly.  
e. What are the stopping rules with regard to efficacy and safety? 
As the target enrollment is 49 subjects per group, and we see hundreds of adult patients 
monthly for acute pain, we do not anticipate needing to stop the trial early.  All adverse events 
will be reviewed and the study will be stopped immediately if we determine the AE was directly 
related to the subject’s participation in the study.   
 
III. 
Analysis Plan 
 
Describe statistical analysis methods as appropriate.  For example, will intention-to-
treat methodology be used in the analysis?  Will there be any sample stratification? 
 
Descriptive statistics, including means, standard deviations, medians, interquartile ranges 
and percentages will be calculated for baseline variables. Comparisons of continuous 
parametric variables will be done using a t test. Non-parametric data will be expressed as a 
median and analyzed using the Mann–Whitney test. A Chi-square test or Fischer's exact test will 
be used to compare categorical variables as appropriate. A bivariate analysis will be performed 
to assess differences between SDK regimens. A P value < 0.05 will be considered significant. 
Microsoft Excel software and STATA version 12 will be used for data analysis.