Clinical trial NCT04860804
Conditions: Pain
Keywords: Emergency Medicine, Pain, Pain Management, Musculoskeletal Emergency Medicine Pain Pain Management Musculoskeletal
Sponsor: Antonios Likourezos
Start date: 2021-04-22; Completion date: 2021-12-31
Enrollment: 60 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Acute Pain is one of the most frequent chief complaints and the main reason for visiting the Emergency Department (ED). The acute pain in the ED is largely prevalent across the country with recent literature demonstrating that 61-91% of patients are admitted to the ED due to a variety of acute painful syndromes. There is a lack of good options for pain control in such settings.

Detailed description:
STUDY OBJECTIVES: To compare analgesic efficacy and rates of side effects of a proprietary formulation of orally administered aspirin and ketamine (AOK) to a proprietary formulation of Oral Ketamine (OK) (VTS-K formulations) for pain management in adult ED patients presenting to the ED with acute musculoskeletal pain HYPOTHESIS: The investigators hypothesize that the administration of AOK will provide better analgesia at 60 minutes post-administration in comparison to OK in adult patients presenting to the ED with acute musculoskeletal pain. The primary outcome of this trial is the comparative reduction in participant's pain scores at 60 minutes post-medication administration.

STUDY DESIGN:

Subjects: Patients 18 years of age and older presenting to the ED with acute musculoskeletal painful conditions (traumatic and non-traumatic) with an initial pain score of 5 or more on a standard 11-point (0 to 10) numeric rating scale and requiring oral analgesia as determined by the treating attending physician. Patients' screening and enrollment will be performed by study investigators and research assistants. All patients will be enrolled at various times of the day when study investigators will be available for patient enrollment and an ED pharmacist will be available for medication preparation.

Design: This is a prospective, randomized, open-label trial comparing analgesic efficacy and safety of AOK and OK in patients presenting to the ED of Maimonides Medical Center with acute musculoskeletal pain. Upon meeting the eligibility criteria, patients will be randomized into one of the two study arms: Group I will receive AOK and Group II will receive OK.

Data Collection Procedures: Each patient will be approached by a study investigator for acquisition of written informed consent and Health Insurance Portability and Accountability Act authorization after being evaluated by the treating emergency physician and determined to meet study eligibility criteria. When English will not be the participant's primary language, a language- appropriate consent form will be used and non-investigator, hospital employed, trained interpreters or licensed telephone interpreters will assist in acquisition of informed consent. Baseline pain score will be determined with an 11-point numeric rating scale (0 to 10), described to the patient as "no pain" being 0 and "the worst pain imaginable" being 10. A study investigator will record the patient's body weight and baseline vital signs. All data will be recorded on data collection sheets, including patients' sex, demographics, medical history, and vital signs, and entered into SPSS (version 24.0; IBM Corp) by the research manager. Confirmation of written consent acquisition for all participants, and statistical analyses will be conducted by the statistician, who will work independently of any data collection.

Expected Outcomes: The primary outcome will include a reduction from baseline of pain scores on numeric rating pain scale (NRS) at 60 minutes. The secondary outcomes will include a need for rescue analgesia and rates of adverse up to 120 minutes. With respect to unique adverse effects of SDK, we will use Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) and Richmond Agitation Sedation Scale (RASS). SERSDA Scale includes fatigue, dizziness, nausea, headache, feeling of unreality, changes in hearing, mood change, general discomfort, and hallucinations with severity of each graded by patients on a five-point scale, with "0" representing the absence of any adverse effects and "4" representing a severely bothersome side effect. RASS evaluates the severity of agitation and/or sedation in accordance to the nine-point scale with scores ranging from "-4" (deeply sedated) to "0" (alert and calm) to "+4" (combative).

Arms: arm 1: Drug: Proprietary oral formulation of 0.5mg/kg of ketamine + 324mg of aspirin arm 2: Drug: Proprietary oral formulation of 0.5mg/kg of ketamine
Interventions: intervention 1: Aspirin and Ketamine intervention 2: Oral Ketamine
Intervention descriptions: intervention 1: Drug: Proprietary oral formulation of 0.5mg/kg of ketamine + 324mg of aspirin intervention 2: Proprietary oral formulation of 0.5mg/kg of ketamine

Protocol documents:
Prot_SAP_000.pdf: 
Maimonides Medical Center Protocol v1.0 March 23, 2021 
 Page 1 of 3 
 
 
 
 
TITLE:  
A comparison of a Combination of Aspirin and Oral Ketamine (VTS-K formulation)  to Oral 
Ketamine alone in adult patients presenting to the ED with acute musculoskeletal pain: 
prospective, randomized, open-label, clinical trial. 
 
 
 
 
NCT#: 
 
 
 
Document Date: March 23, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Maimonides Medical Center Protocol v1.0 March 23, 2021 
 Page 2 of 3 
 
TITLE:  
A comparison of a Combination of Aspirin and Oral Ketamine (VTS-K formulation)  to Oral 
Ketamine alone in adult patients presenting to the ED with acute musculoskeletal pain: 
prospective, randomized, open-label, clinical trial. 
 
 
INTRODUCTION 
 
Acute Pain is one of the most frequent chief complaints and the main reason for visiting the Emergency  
Department (ED). The acute pain in the ED is largely prevalent across the country with recent literature  
demonstrating that 61-91% of patients are admitted to the ED due to a variety of acute painful syndromes. There 
is a lack of good options for pain control in such settings.  
 
 
STUDY OBJECTIVES 
 
To compare analgesic efficacy and rates of side effects of a proprietary formulation of orally administered aspirin 
and ketamine (AOK) to a proprietary formulation of Oral Ketamine (OK) (VTS-K formulations) for pain 
management in adult ED patients presenting to the ED with acute musculoskeletal pain 
 
 
HYPOTHESIS  
 
We hypothesize that the administration of AOK will provide better analgesia at 60 minutes post-administration 
in comparison to OK in adult patients presenting to the ED with acute musculoskeletal pain. The primary 
outcome of this trial is the comparative reduction in participant’s pain scores at 60 minutes post-medication 
administration.  
 
STUDY DESIGN 
 
Subjects: Patients 18 years of age and older presenting to the ED with acute musculoskeletal painful conditions 
(traumatic and non-traumatic) with an initial pain score of 5 or more on a standard 11- point (0 to 10) numeric 
rating scale and requiring oral analgesia as determined by the treating attending physician. Patients’ screening 
and enrollment will be performed by study investigators and research assistants. All patients will be enrolled at 
various times of the day when study investigators will be available for patient enrollment and an ED pharmacist 
will be available for medication preparation. 
 
Eligibility Criteria: Patients 18 years of age and older presenting to the ED with acute musculoskeletal painful 
conditions (traumatic and non-traumatic) with an initial pain score of 5 on a standard 11- point (0 to 10) numeric 
rating scale. Patients will have to be awake, alert, and oriented to person, place, and time, and will be able to 
demonstrate understanding of the informed consent process and content. Patients also will have to demonstrate 
ability to verbalize the nature of any adverse effects they might experience as well as to express their pain severity 
by using the NRS. 
  
Exclusion Criteria: Patients with altered mental status, allergy to aspirin and ketamine, pregnant patients, 
unstable vital signs (systolic blood pressure <90 or>180 mm Hg, pulse rate <50 or >150 beats/min, and respiration 


Maimonides Medical Center Protocol v1.0 March 23, 2021 
 Page 3 of 3 
 
rate <10 or >30 breaths/min), inability to provide consent, consumption of Aspirin or NSAID’s within 6 hours of 
arrival to the ED, active PUD, history of GI Hemorrhage, history of renal and hepatic insufficiency, past medical 
history of alcohol or drug abuse, or schizophrenia. 
 
Design: This is a prospective, randomized, open-label trial comparing analgesic efficacy and safety of AOK and 
OK in patients presenting to the ED of Maimonides Medical Center with acute musculoskeletal pain. Upon 
meeting the eligibility criteria, patients will be randomized into one of the two study arms: Group I will receive 
AOK and Group II will receive OK.  
 
Data Collection Procedures: Each patient will be approached by a study investigator for acquisition of written 
informed consent and Health Insurance Portability and Accountability Act authorization after being evaluated by 
the treating emergency physician and determined to meet study eligibility criteria. When English will not be the 
participant’s primary language, a language- appropriate consent form will be used and non-investigator, hospital-
employed, trained interpreters or licensed telephone interpreter will assist in acquisition of informed consent.  
Baseline pain score will be determined with an 11-point numeric rating scale (0 to 10), described to the patient as 
“no pain” being 0 and “the worst pain imaginable” being 10. A study investigator will record the patient’s body 
weight and baseline vital signs. All data will be recorded on data collection sheets, including patients’ sex, 
demographics, medical history, and vital signs, and entered into SPSS (version 24.0; IBM Corp) by the research 
manager. Confirmation of written consent acquisition for all participants, and statistical analyses will be 
conducted by the statistician, who will work independently of any data collection. 
 
Data Analysis:  Data analyses will include frequency distributions and independent-sample t-test to assess 
differences in pain scores at the various intervals. Mixed-model linear regression will be used to compare changes 
in pain numeric rating scale across time points. For categorical outcomes (eg, complete resolution of pain), a X2 
or Fisher’s exact test will be used to compare outcomes at 60 minutes. Based on the validation of a verbally 
administered rating scale of acute pain in the ED and the comparison of verbal and visual pain scales, we will use 
a primary outcome consisting of a minimal clinically meaningful difference of 2 between two groups at the 60-
minute pain assessment.   
 
Sample Size: Assuming 3.0 SD, alpha of 0.05 and 80% power, we will need 29 patients per group to detect a 
superiority of AOK with minimal statistically significant difference of 2.0 at 60 min. 
 
Expected Outcomes: The primary outcome will include a reduction from baseline of pain scores on numeric 
rating pain scale (NRS) at 60 minutes.  The secondary outcomes will include a need for rescue analgesia and rates 
of adverse up to 120 minutes.  
 
Adverse Events: 
With respect to unique adverse effects of SDK, we will use Side Effect Rating Scale for Dissociative Anesthetics 
(SERSDA) and Richmond Agitation Sedation Scale (RASS).  SERSDA Scale includes fatigue, dizziness, nausea, 
headache, feeling of unreality, changes in hearing, mood change, general discomfort, and hallucinations with 
severity of each graded by patients on a five-point scale, with “0” representing the absence of any adverse effects 
and “4” representing a severely bothersome side effect. RASS evaluates the severity of agitation and/or sedation 
in accordance to the nine-point scale with scores ranging from “−4” (deeply sedated) to “0” (alert and calm) to 
“+4” (combative).