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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 : Completed
First Posted : September 28, 2017
Results First Posted : April 20, 2021
Last Update Posted : April 20, 2021
Sponsor:
Information provided by (Responsible Party):
UCSF Benioff Children's Hospital Oakland

Tracking Information
First Submitted Date  ICMJE January 9, 2017
First Posted Date  ICMJE September 28, 2017
Results First Submitted Date  ICMJE November 17, 2020
Results First Posted Date  ICMJE April 20, 2021
Last Update Posted Date April 20, 2021
Study Start Date  ICMJE June 2016
Actual Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2021)
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 18 months ]
The number of serious and minor adverse events was measured via patient-completed survey as well as by nurse and medical providers on presentation to the emergency department (ED). 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. Both study providers and patients themselves, via a survey that the parent and/or patient (based on age) fills out post receipt of ketamine, reported serious and minor adverse events.
Original Primary Outcome Measures  ICMJE
 (submitted: September 23, 2017)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2021)
  • Effect of Low-dose Ketamine (LDK) on Opioid Usage in the ED [ Time Frame: Up to one year prior and after LDK administration on day 1 of the study in the ED ]
    Opioid usage for at least one but up to three prior patient visits in the last one year for each patient enrolled in the study was summarized, expressed as morphine equivalents in mg/kg/h, to account for different types of opioids used per patient preference, and then this was compared to the intervention group that received LDK. Percent change in opioid usage (expressed as morphine equivalents in mg/kg/h) is reported).
  • Effect of Low-dose Ketamine on Pain Scores on Presentation to the ED [ Time Frame: Up to one year prior and on presentation to the ED after LDK administration ]
    Patient pain scores at presentation for the enrolled encounters and for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. At least one but up to three prior visits were averaged and compared to the intervention visit. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).
  • Effect of Low-dose Ketamine on Discharge Rates From the ED [ Time Frame: Up to one year prior to receipt of ketamine for the historical control arm/group and up to 18 months for the intervention arm/group ]
    Percent discharge from the ED for intervention group and for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. Participants were assigned a "0" if discharged or "1" if not discharged.
  • Subjective Effect of Low Dose Ketamine on Pain Relief Assessed Via a Patient Survey [ Time Frame: after LDK administration on day 1 of the study in the ED ]
    After receipt of LDK, patients and/or their parents, based on age, filled out a survey based on a Likert scale regarding their agreement (Strongly Disagree to Strongly Agree) with the following statements: Achieved faster pain relief with LDK, Achieved more complete pain relief with LDK, and Desire to receive LDK in a future vaso-occlusive crisis. There is also an area where patients could provide general comments regarding their experience in receiving LDK. Count of Participants who agree or strongly agree for each question are reported.
  • Effect of Low-dose Ketamine on Patient Pain Scores on Discharge From the ED/Admission to the Hospital [ Time Frame: At time of discharge from the ED/admission to the hospital (up to one year prior and after LDK administration) ]
    Patient pain scores at time of discharge from the ED/admission to the hospital for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. At least one but up to three prior visits were averaged and compared to the intervention visit. Pain scores post receipt of ketamine are presented for the intervention group. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).
  • Effect of Low-dose Ketamine on Percent Difference of Length of Stay (LOS) in the ED [ Time Frame: Up to one year prior to and after LDK administration on day 1 of the study in the ED ]
    Length of stay (LOS) in minutes in the ED for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed.
  • Effect of Low-dose Ketamine on Time to 50% Pain Reduction [ Time Frame: Up to one year prior to and after LDK administration on day 1 of the study in the ED ]
    Time to 50% pain reduction (pain reported 50% less than baseline) in minutes for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed as historical controls. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).
Original Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso-occlusive Crisis
Official Title  ICMJE Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso-occlusive Crisis (AKTSS)
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.
Detailed Description In this cohort study, all consenting pediatric sickle-cell patients between 10 and 25 years old who were cared for at UCSF Benioff Children's Hospital Oakland (UCSFBCHO) presenting to the emergency department for VOC were enrolled in the study. Patients were 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 was 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 was summed in the ED, converted to mg/kg/hour of morphine equivalents (since different opioids agents were 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, length of stay, time to 50% pain control, presentation and discharge pain scores, and likelihood of discharge from the ED were compared. Data was 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) was compared to the post intervention data. In addition, a survey, which is attached, was 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. Monitoring for adverse events was recorded for each patient encounter.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Sickle Cell Disease
  • Vaso-Occlusive Crisis
Intervention  ICMJE Drug: Ketamine
The intervention is IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs).
Other Name: Ketalar
Study Arms  ICMJE
  • Active Comparator: Intervention

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

    In addition, a survey, which is attached, was 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.

    Intervention: Drug: Ketamine
  • No Intervention: Historical Control
    Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 25, 2021)
62
Original Estimated Enrollment  ICMJE
 (submitted: September 23, 2017)
90
Actual Study Completion Date  ICMJE April 2018
Actual Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 were asked to enroll.

Exclusion Criteria:

  • Prior adverse reaction to ketamine
  • Patients were 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 was not 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 did not receive ketamine.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03296345
Other Study ID Numbers  ICMJE 2010-010
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party UCSF Benioff Children's Hospital Oakland
Study Sponsor  ICMJE UCSF Benioff Children's Hospital Oakland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jonathan B Cooper-Sood, MD Children's Hospital and Research Center of Oakland
PRS Account UCSF Benioff Children's Hospital Oakland
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP