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Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso-occlusive Crisis (AKTSS)

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ClinicalTrials.gov Identifier: NCT03296345
Recruitment Status : Recruiting
First Posted : September 28, 2017
Last Update Posted : September 28, 2017
Sponsor:
Information provided by (Responsible Party):
Bryan Cooper-Sood, UCSF Benioff Children’s Hospital Oakland

Brief Summary:
Acute vaso-occlusive episodes (VOEs) in sickle cell disease (SCD) are primarily managed with opioids. Tolerance and hyperalgesia to opioids develops due to N-methyl-D-aspartate (NMDA)-receptor mediated activation of the nociceptive system, and as a receptor antagonist, ketamine mitigates this. Intravenous (IV) ketamine has demonstrated efficacy in reducing post-operative, chronic, and cancer-related pain in pediatrics, as well as in reducing time to pain control in the emergency department (ED) in adults. Limited studies suggest efficacy in adult opioid-refractory SCD patients. This study is investigating the safety and tolerability of adjuvant low-dose IV ketamine bolus for pediatric SCD VOE in the ED, as well as its efficacy in improving pain control and reducing hospitalization.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Vaso-Occlusive Crisis Drug: Ketamine Phase 2

Detailed Description:
In this cohort study, all consenting pediatric sickle-cell patients between 10 and 25 years old who are cared for at UCSF Benioff Children's Hospital Oakland (UCSFBCHO) presenting to the emergency department for VOC will be enrolled in the study. Patients will be compared to themselves in a time series, pre and post exposure to the study intervention (low-dose ketamine bolus at 0.2 mg/kg x 1 prior to second dose of IV opiate) The pediatric FACES pain scale will be used to measure pain scales at pre-designated time points in the ED per standard nursing protocol (FACES for younger kids, visual analog scale in adolescents/young adults). Opiate usage will be summed in the ED, converted to mg/kg/hour of morphine equivalents (since different opiate agents are given to different patients based on individual historical efficacy, and since length of stay in the emergency room could affect total morphine equivalents received), and compared between the pre and post-intervention groups. In addition, the proportion of discharged vs admitted patients, pain scores at admission, during the visit, and discharge, and proportion of patients re-presenting for care, will all be compared in the pre and post intervention groups. Data will be collected via chart review in the UCSFBCHO system by study investigators. Pre-intervention data from the past three patient encounters (e.g., the mean of the mg/kg/hour of morphine equivalents used in the last three patient encounters prior to receipt of ketamine) will be compared to the post intervention data. In addition, a survey, which is attached, will be given to patients/families at the time of the drug administration to attempt to discern if patients subjectively experienced improvement in their pain and if they experienced any negative side effects due to the drug administration.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso-occlusive Crisis (AKTSS)
Study Start Date : June 2016
Actual Primary Completion Date : January 2017
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Active Comparator: Intervention

Prior to the second dose of IV opiates, the experiment will be to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Pain scores will be collected using the FACES scale currently in place. In consenting patients, chart review will be performed with the following data being collected: mg/kg/hour of morphine equivalents, pain scores on admission, during the encounter, and at discharge, the time to 50% pain reduction, whether or not the patient was discharged, and if re-presentation occurred in the subsequent 3 months.

In addition, a survey, which is attached, will be given to patients/families at the time of drug administration to determine if they experienced a subjective improvement in their pain and if they suffered any undue side effects due to drug administration.

Drug: Ketamine
The intervention is IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs).

No Intervention: Historical Control
Patient data from at least one but up to as many as are available within the last year will be summed and compared to their visit where they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients act as their own controls in the above manner. Patients are allowed to re-enroll 4 weeks after presentation, which is typically considered a second vaso-occlusive crisis in the literature.



Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 6 months ]
    Serious adverse events are defined as cardiorespiratory events requiring intervention. Minor adverse events are defined as nausea/vomiting, emergence reaction (dysphoria; hallucinations; frightening dreams), and a sense of de-realization or "dreamy" sensation. The incidence of treatment-emergence adverse events will be expressed in percentages and reviewed by our DSMB and IRB, in comparison to the incidence of treatment-emergent adverse events published in the adult literature (none currently exists in the pediatric literature for comparison). Both study providers and patients themselves, via a survey that the parent and/or patient (based on age) fills out post receipt of ketamine, will report serious and minor adverse events. Per the decision of the UCSF Benioff Children's Hospital and Research Center of Oakland IRB and Research Committee, at least 30 patients are required to complete this outcome.


Secondary Outcome Measures :
  1. Effect of low-dose ketamine on opiate usage in the ED [ Time Frame: Up to 18 months ]
    Opiate usage for at least one but up to as many available prior patient visits in the last one year for each patient enrolled in the study will be summarized, expressed as morphine equivalents in mg/kg/h, to account for different types of opiates used per patient preference and time spent in the ED. This will be compared via a t-test to determine if a significant difference exists pre and post intervention with ketamine. To detect a 20% difference, 90 patients must be enrolled.

  2. Effect of low-dose ketamine on pain scores in the ED [ Time Frame: Up to 18 months ]
    Patient pain scores at presentation, discharge from the ED/admission to the hospital, and time to 50% pain reduction in minutes for at least one but up to as many patient encounters prior to receipt of ketamine in the last one year, will be assessed. Pain scores and time to pain reduction as above will be compared via a t-test pre and post receipt of ketamine.

  3. Effect of low-dose ketamine on hospitalization and discharge rates from the ED [ Time Frame: Up to 18 months ]
    The average hospitalization and discharge rates, expressed as percentages, for all patients in the study pre and post receipt of ketamine will be calculated. These will be compared via a t-test to determine if a significant difference exists.

  4. Subjective effect of low dose ketamine on pain relief assessed via a patient survey [ Time Frame: Up to 18 months ]
    After receipt of ketamine, patients and/or their parents, based on age, will fill out a survey based on a Likert scale regarding their agreement with the following questions: if ketamine relieved their pain faster, if ketamine relieved their pain more completely, and if they would like to receive ketamine for a future vaso-occlusive crisis. There is also an area where patients can provide general comments regarding their experience in receiving ketamine.



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Ages Eligible for Study:   8 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • All English-speaking, sickle cell patients who receive their care at UCSFBCHO in the Department of Hematology who are 8-to-25-years-old presenting to the emergency department for VOC will be asked to enroll.

Exclusion Criteria:

  • Prior adverse reaction to ketamine.
  • Patients will be asked during the consent process if they have ever received ketamine, and if so, if they had any serious adverse reaction, such as difficulty breathing, dysphoria, hallucinations, or allergic reaction. If they have, ketamine will not be given to these patients.
  • Patients who have received ketamine and experienced nausea or vomiting will be asked if they wish to receive the medication. If they do not, they will not receive ketamine.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03296345


Contacts
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Contact: Bryan Cooper-Sood, MD 5104283888 jocooper@mail.cho.org
Contact: Anurag Agrawal, MD 5104283539 AAgrawal@mail.cho.org

Locations
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United States, California
UCSF Benioff Children's Hospital and Research Center Oakland Recruiting
Oakland, California, United States, 94609
Contact: Bryan Cooper-Sood, MD    510-428-3888    jocooper@mail.cho.org   
Contact: Anurag Agrawal, MD    5104283539    AAgrawal@mail.cho.org   
Principal Investigator: Bryan Cooper-Sood, MD         
Sub-Investigator: Anurag Agrawal, MD         
Sub-Investigator: Carolyn Hoppe, MD         
Sub-Investigator: James Naprawa, MD         
Sub-Investigator: Anne Marsh, MD         
Sponsors and Collaborators
UCSF Benioff Children’s Hospital Oakland

Publications:

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Responsible Party: Bryan Cooper-Sood, Pediatric Emergency Medicine Fellow, UCSF Benioff Children’s Hospital Oakland
ClinicalTrials.gov Identifier: NCT03296345     History of Changes
Other Study ID Numbers: 2010-010
First Posted: September 28, 2017    Key Record Dates
Last Update Posted: September 28, 2017
Last Verified: September 2017

Keywords provided by Bryan Cooper-Sood, UCSF Benioff Children’s Hospital Oakland:
Ketamine
Sickle Cell Disease
Vaso-Occlusive Crisis

Additional relevant MeSH terms:
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Ketamine
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action