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Low-Dose Ketamine Infusion for Children With Sickle Cell Disease-Related Pain

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ClinicalTrials.gov Identifier: NCT00595530
Recruitment Status : Terminated (Lack of enrollment and patient interest in study)
First Posted : January 16, 2008
Results First Posted : March 30, 2016
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
William Zempsky, MD, Connecticut Children's Medical Center

Tracking Information
First Submitted Date  ICMJE December 27, 2007
First Posted Date  ICMJE January 16, 2008
Results First Submitted Date  ICMJE July 27, 2015
Results First Posted Date  ICMJE March 30, 2016
Last Update Posted Date August 21, 2019
Actual Study Start Date  ICMJE March 4, 2008
Actual Primary Completion Date February 12, 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2019)
Number of Participants With Improvement in Pain Scores of >2 Points on the Pain Scale [ Time Frame: Baseline then daily while inpatient, up to 72 hours ]
Determine if there is an apparent improvement in pain control with the ketamine infusion based on the investigator's discretion and comparison to past pain scores. Pain was scored on a scale from 0 to 10. Zero equaled no pain and 10 equaled a lot of pain.
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2008)
Side effects [ Time Frame: Continuous ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2019)
Number of Participants Who Showed a Reduction of Opioid Utilization While on IV Ketamine [ Time Frame: Baseline then daily while inpatient, up to 72 hours ]
Looking at the reduction of opioid utilization while on IV Ketamine. Three participants were enrolled in the study, therefore a comprehensive analysis could not be done due to the low enrollment.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2008)
  • Intravenous opiate utilization [ Time Frame: Every 4 hours ]
  • Self-reported pain scores [ Time Frame: Every 4 hours ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low-Dose Ketamine Infusion for Children With Sickle Cell Disease-Related Pain
Official Title  ICMJE Use of Low-Dose Ketamine Infusion in Acute Painful Episodes of Sickle Cell Disease: A Pilot Study
Brief Summary Acute pain episodes associated with sickle cell disease (SCD) are very difficult to manage effectively. Opioid tolerance and side effects have been major roadblocks in our ability to provide these patients with adequate pain relief. This pilot study is designed to examine the safety and feasibility of using ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, in the inpatient seeing with children and adolescents who have sickle cell vasoocclusive pain. Previous research suggests that in subanesthetic doses, ketamine may be able to prevent the development of opiate tolerance and facilitate better pain relief with lower opiate doses, allowing for less respiratory depression, less sedation, easier ambulation, less deconditioning, shorter hospital stays, and better quality of life. The goal of this pilot study is to evaluate the safety and feasibility of using a continuous infusion of ketamine, in conjunction with opiates, in the inpatient setting for sickle cell vasoocclusive pain. It is hypothesized that using a low dose ketamine infusion in conjunction with opiates will be a safe and feasible practice for the treatment of sickle cell pain.
Detailed Description

3.2 Study Design/Type

  1. Patient meeting inclusion/exclusion criteria is enrolled up to 24 hours after admission for a vasoocclusive episode.
  2. Prior to onset of ketamine infusion, the following information is collected:

    1. Demographic information (age, gender, SCD genotype, past history of SCD-related complications) [Obtained from the patient's medical chart]
    2. Opiate utilization/hour since admission [Obtained from the patient's medical chart]
    3. Numerical Rating Scale (NRS) scores since admission [Obtained from the patient's medical chart]
    4. Sedation score (University of Michigan Sedation Scale) is obtained [By the nursing staff]
    5. Body outline figure of the Adolescent Pediatric Pain Tool (validated down to age 7) is administered [By the research staff]
    6. Ketamine Effects Scale (KES) is administered to the patient [By the research staff]
  3. Ketamine infusion is begun at 0.05 mg/kg/hour.
  4. After infusion is initiated:

    1. Vital signs are taken every hour for two hours after infusion begins, then after two hours, then every four hours for the remainder of the hospitalization [Completed by the nursing staff]
    2. Pain scores are recorded with vital signs if the patient is awake [Completed by nursing staff]
    3. Patient is also asked if pain is a lot better, a little better, no change, a little worse, or a lot worse than previous assessment [Completed by nursing staff]
    4. Sedation score (University of Michigan Sedation Scale) assessed with pain score [Completed by the nursing staff]
    5. Adolescent Pediatric Pain Tool (APPT) body outline figure is completed by the patient once per day between 3 pm and 5 pm. [Administered by the research staff]
    6. Ketamine Effects Scale (KES) is administered to the patient once per day between 3pm and 5pm [By the research staff]
    7. Patient is monitored for side effects including dreams, disorientation, dysphoria, agitation, CNS depression, respiratory depression, increasing hypoxia, nausea, or vomiting [Completed by the nursing or research staff]
    8. Need for supplemental oxygen is recorded (oxygen saturation <95%) [Completed by nursing staff]
    9. Opiate use and NSAID use/6 hours is recorded [Completed by the nursing or research staff]
  5. The infusion may be discontinued or decreased at any time due to unacceptable side effects as determined by the clinician, patient, parent, or principal investigator.
  6. Agents designed to reduce ketamine side effects [midazolam (Versed), clonidine, lorazepam (Ativan), or diazepam (Valium)] may be administered at the discretion of the attending physician or the principal investigator.
  7. 4 hours or more after infusion begins, the infusion rate may be increased to 0.1 mg/kg/hour if the following parameters are met:

    1. patient's pain has not improved to an acceptable range (pain score is still ≥5)
    2. side effects remain acceptable
  8. 4 hours or more after the previous increase the ketamine infusion may be increased to 0.15 mg/kg/hour per parameters.
  9. 4 hours of more after the previous increase the ketamine infusion may be increased to 0.2 mg/kg/hour per parameters.
  10. The ketamine infusion will be discontinued at the time of transition to oral pain medication, or no more than 72 hours after initiation, or at the request of the clinician, patient, parent, or principal investigator.
  11. Pain scores, vital signs, sedation score, opiate use, APPT body outline figure, and KES score will be recorded as above for the remainder of the hospitalization.
  12. Total length of hospitalization will be recorded.
  13. Patient will be contacted on a weekly basis for 4 weeks following hospitalization for review of potential side effects, pain episodes, or events leading to re-admission.
  14. The patient's medical record will be reviewed to determine duration of previous hospitalizations for SCD pain in the previous 24 months and opiate utilization, pain scores, and transition to oral opiates during those hospitalizations.

3.3 Randomization

This will be conducted as a pilot study; patients will not be randomized.

3.4 Duration

The length of the patient's participation in this study is the duration of their hospitalization, as well as 4 weeks worth of follow-up phone calls.

3.5 Discontinuation

Individual patients will stop receiving ketamine if they develop acute chest syndrome (ACS), have a stroke, are transferred to the Intensive Care Unit (ICU), if their hemoglobin falls below 5 mg/dl, if they experience unacceptable side effects, or at the request of the PI, attending, patient, or parent. However, they will continue to be in the study and all data will be collected throughout the duration of their hospitalization.

The entire trial will be terminated when 20 patients have completed the protocol, or if there is an unexpected rate of acute chest syndrome or admissions to the pediatric intensive care unit (PICU).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE Drug: ketamine

Medication administered via IV. This study will utilize 4 doses of ketamine: 0.05 mg/kg/hr, 0.1 mg/kg/hr, 0.15 mg/kg/hr, and 0.2 mg/kg/hr.

Dosing Regimen:

  • Patients begin the ketamine infusion at 0.05 mg/kg/hr.
  • 4 or more hrs after infusion is started, the dose may be increased to 0.1 mg/kg/hr if:

    1. patient's pain has not improved to an acceptable level
    2. side effects remain acceptable
  • 4 hrs or more after the previous increase, the dose may be adjusted to 0.15 mg/kg/hr
  • 4 hrs or more after the previous increase, the dose may be adjusted to 0.2 mg/kg/hour
  • Maximum dose of ketamine is limited to 300 mg per 24 hrs

Patient may receive ketamine up to 72 hrs after initiation.

Other Name: Ketalar
Study Arms  ICMJE Experimental: Ketamine
This group will receive ketamine
Intervention: Drug: ketamine
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: February 8, 2012)
3
Original Estimated Enrollment  ICMJE
 (submitted: January 7, 2008)
10
Actual Study Completion Date  ICMJE February 12, 2010
Actual Primary Completion Date February 12, 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • CCMC: Children ages 7-22 years (inclusive) with documented sickle cell disease
  • UCHC: Adults 18 years (inclusive) and above with documented sickle cell disease
  • Sudden onset of acute pain consistent with a vasoocclusive episode -Pain requiring hospitalization, placement on pain protocol, and patient- controlled opiates
  • Pain score of greater than or equal to 5 out of 10 when ketamine infusion is started
  • Cognitive ability to report pain on a 0 to 10 Numerical Rating Scale (NRS)
  • At least one prior hospitalization for vasoocclusive pain at CCMC in the previous 24 months
  • Parental consent and child assent

Exclusion Criteria:

  • Children hospitalized for a primary diagnosis other than vasoocclusive episode
  • Concurrent Acute Chest Syndrome (ACS)
  • Hemoglobin < 5 mg/dL
  • Concurrent history of glaucoma or raised intracranial pressure
  • Signs or symptoms consistent with stroke
  • History of liver or renal dysfunction
  • Pregnancy (females age 12 and above must have pregnancy test)
  • Simultaneous participation in investigational drug study
  • Primary language spoken other than English
  • No hospitalizations to CCMC for vasoocclusive pain in the previous 24 months
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
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 NCT00595530
Other Study ID Numbers  ICMJE 07-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: There is no plan to share data as the low enrollment makes the results of this study non-generalizable.
Responsible Party William Zempsky, MD, Connecticut Children's Medical Center
Study Sponsor  ICMJE Connecticut Children's Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: William T Zempsky, MD Connecticut Children's Medical Center
PRS Account Connecticut Children's Medical Center
Verification Date August 2019

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