Oral Ketamine for Treatment of Vaso-Occlusive Pain

Study Overview
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Brief Summary
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The purpose of this study is to learn more about the feasibility of oral ketamine for the treatment of painful sickle-cell crises in children and adolescents as a supplement to intravenous (IV) opioids. There is a need for improved non-opioid analgesia for patients experiencing sickle-cell crises in the hospital and prehospital setting, as children and adolescents with sickle cell disease who experience sickle-cell crises often have severe pain that is not well controlled by high dose opioids, leading to poor pain management and opioid-related side effects. The study will begin when patients are admitted to the Emergency Department of Boston Children's Hospital for treatment of a sickle-cell crisis. Oral ketamine will be administered every 8 hours for the next 48 hours. Patients will have continuous cardiorespiratory monitoring for the duration of the study, as per routine care, as well as monitoring by the hospital's Acute Pain Service at least twice daily for pain management and side effects of pain treatment. At the end of the 48-hour study duration, patients will discuss with the Pain Service and Hematology Service whether to continue oral ketamine, change to intravenous ketamine, or discontinue ketamine based on clinical indications such as level of pain and sedation while on opioids.

Detailed Description
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This is a pilot study of the feasibility of oral ketamine dosing initiated in the Emergency Department and continued for 48 hours for adolescents and young adults hospitalized with VOCs. A total of 10 patients between the ages of 12 and 24 years will receive oral ketamine 0.5 mg/kg Q8hrs for 48 hours. Pain scores using VAS and Modified Ramsey Sedation Scores will be obtained every 4 hours per routine nursing care. Vital signs (temperature, heart rate, blood pressure, and respiratory rate) will also be taken every 4 hours throughout the study duration. Side effects (such as dysphoria, dizziness, unpleasant dreams, hallucinations, headache, and nausea) will be monitored throughout the study duration. The Acute Pain Service will assess each patient at least twice daily for pain management and side effects to pain treatment. Ketamine will be discontinued for patients who experience side effects. Patients who experience continued high pain scores will have the option of having oral ketamine discontinued and IV ketamine infusion initiated. At the end of the 48 hour study period, patient, parent, Pain Service and Hematology Service will discuss whether to continue oral ketamine, change to intravenous ketamine, or discontinue ketamine based on clinical indications such as level of pain and sedation while on opioids. Patients and parents (for patients > 18 years) will be asked to complete a brief satisfaction survey at the end of the 48 hour study period. Patients who are 12-24 years of age who require admission for vaso-occlusive pain will be included. Patients who do not wish to participate or who have had side effects to previous use of intravenous ketamine for treatment of vaso-occlusive pain that would preclude using ketamine for future pain episodes will not be included in this study.

Official Title
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A Pilot Study of the Use of Oral Ketamine for Treatment of Vaso-Occlusive Pain in Adolescents and Young Adults

Conditions
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Vaso-occlusive Crisis

Intervention / Treatment
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* Drug: Ketamine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 12-24 years of age who require admission for vaso-occlusive pain Exclusion Criteria: Patients who have had side effects to previous use of intravenous ketamine for treatment of vaso-occlusive pain that would preclude using ketamine for future pain episodes. Patient refusal to participate

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All patients in this study will receive oral ketamine for the treatment of pain from vaso-occlusive crisis.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine<br> | Drug: Ketamine Hydrochloride<br>* All patients in this study will receive oral ketamine for the treatment of pain from vaso-occlusive crisis. Patients will receive 0.5 mg/kg ketamine Q8hrs for 48 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain intensity scores using the Visual Analogue Scale (VAS) Pain Score Scale | The Visual Analog Scale (VAS) will be used to measure pain. Scores are recorded on a line that represents a continuum between no pain and worst pain. | Baseline, and then every 4 hours for 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sedation Scores using modified Ramsey Sedation Scores Scale | The Ramsay Sedation Scale used as a measure of sedation allows for a numeric score from 1 to 6, based on responsiveness of the patient. The scale divides a patient's level of sedation into six categories ranging from severe agitation to deep coma. | Baseline, and then every 4 hours for 48 hours | 
| Number of patients with abnormal vital signs | Vital signs data (blood pressure, heart rate, respiratory rate, and temperature) will be collected and number of patients with abnormal vital signs will be reported. | Baseline, and then every 4 hours for 48 hours | 
| Frequency of side effects | Side effects such as dysphoria, dizziness, unpleasant dreams, hallucinations, headache, nausea will be assessed. | Baseline, and then every 4 hours for 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine, Sickle-cell disease, Opioid-sparing, Analgesia