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Sub-dissociative Intranasal Ketamine for Pediatric Sickle Cell Pain Crises

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ClinicalTrials.gov Identifier: NCT02573714
Recruitment Status : Recruiting
First Posted : October 12, 2015
Last Update Posted : January 29, 2018
Sponsor:
Collaborators:
Carolinas Medical Center
Muhimbili National Hospital
Information provided by (Responsible Party):
Cameroon Baptist Convention Health

Brief Summary:
The purpose of this study is to determine if the use of ketamine, sniffed in the nose, is a safe and effective way to help reduce pain in pediatric sickle cell patients with pain crises in resource-limited settings.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Ketamine Drug: Normal Saline Other: Standard Pain Therapy Other: Pediatric Quality of Life - Sickle Cell Disease Module Other: Faces Pain Scale - Revised Not Applicable

Detailed Description:
This is a randomized, placebo-controlled, drug trial using sub-dissociative intranasal ketamine as an adjunct to standard pharmacotherapy for the management of pediatric sickle cell disease vasoocclusive pain crises in resource-poor settings. Pediatric patients will be enrolled at a teaching and referral hospital in West Africa. Patients will be randomly assigned to the treatment arm - standard therapy plus sub-dissociative intranasal ketamine (1 mg/kg) given at time zero) or the control arm - standard therapy plus intranasal normal saline (volume-matched to treatment arm), and patients will evaluated at standard intervals to assess for pain scores and vital signs (0 minutes, 30 minutes, 60 minutes, and 120 minutes). Pain will be assessed using the Faces Pain Scale - Revised (FPS-R). Patients will also be observed for any potential side effects or adverse events. All patients will be contacted 2-3 weeks post intranasal medication administration for over-the-phone follow-up using a portion of the PedsQL-SCD questionnaire, to assess for basic quality of life related to pain management and treatment.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Comparison of Sub-dissociative Intranasal Ketamine Plus Standard Pain Therapy Versus Standard Pain Therapy in the Treatment of Pediatric Sickle Cell Disease Vasoocclusive Crises in Resource-limited Settings: a Multi-centered, Randomized, Controlled Trial
Study Start Date : December 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Experimental: Intranasal Ketamine
Patients allocated to receive intranasal ketamine (intervention) in addition to standard pain therapy. Patients enrolled in this arm will utilize the FPS-R and follow-up PedsQL-SCD.
Drug: Ketamine
Intranasal ketamine (concentration: 50 mg/ml, dose: 1 mg/kg) will be given at time zero. Intranasal administration will be performed by placing the needleless syringe gently into the nares with the patient sitting upright. Volumes of ≤ 0.75ml will be nasally inhaled in a single nare, while volumes > 0.75ml will be divided between both nares. Patients who are unable to inhale the medication nasally will receive drip administration of the same volume while recumbent on the bed.

Other: Standard Pain Therapy
Typical management strategy for pediatric sickle cell disease vasoocclusive crises including acetaminophen/paracetamol, ibuprofen, oral opioids, and injectable opioids depending on pain severity.

Other: Pediatric Quality of Life - Sickle Cell Disease Module
Standardized quality of life assessment performed 2-3 weeks post intranasal medication administration to evaluate pain management and severity of symptoms after discharge from the hospital.
Other Name: PedsQL-SCD

Other: Faces Pain Scale - Revised
All patients will answer the FPS-R at 0 minutes (immediately prior to receiving intranasal medication), 30 minutes, 60 minutes, and 120 minutes to assess current pain status.
Other Name: FPS-R

Placebo Comparator: Normal Saline
Patients allocated to receive intranasal normal saline (placebo) in addition to standard pain therapy. Patients enrolled in this arm will utilize the FPS-R and follow-up PedsQL-SCD.
Drug: Normal Saline
Intranasal normal saline (placebo: volume-matched with intranasal ketamine) will be given at time zero. Intranasal administration will be performed by placing the needleless syringe gently into the nares with the patient sitting upright. Volumes of ≤ 0.75ml will be nasally inhaled in a single nare, while volumes > 0.75ml will be divided between both nares. Patients who are unable to inhale the medication nasally will receive drip administration of the same volume while recumbent on the bed.
Other Name: NaCl 0.9%

Other: Standard Pain Therapy
Typical management strategy for pediatric sickle cell disease vasoocclusive crises including acetaminophen/paracetamol, ibuprofen, oral opioids, and injectable opioids depending on pain severity.

Other: Pediatric Quality of Life - Sickle Cell Disease Module
Standardized quality of life assessment performed 2-3 weeks post intranasal medication administration to evaluate pain management and severity of symptoms after discharge from the hospital.
Other Name: PedsQL-SCD

Other: Faces Pain Scale - Revised
All patients will answer the FPS-R at 0 minutes (immediately prior to receiving intranasal medication), 30 minutes, 60 minutes, and 120 minutes to assess current pain status.
Other Name: FPS-R




Primary Outcome Measures :
  1. Change from Baseline (time zero) in FPS-R scores between treatment groups [ Time Frame: Baseline (time zero, indicated by injection of intranasal medication), 30 minutes, 60 minutes, and 120 minutes ]
    Measure of differences of change of FPS-R scores from baseline to 30 minutes, 60 minutes, and 120 minutes compared between treatment arms


Secondary Outcome Measures :
  1. Hospital length of stay [ Time Frame: through study completion, an average of 3 days ]
    Hospital length of stay recorded from time zero to time of discharge documented by the study clinician will be a secondary outcome measure.

  2. Quality of life assessment (PedsQL-SCD Module scores) [ Time Frame: Time of first intranasal administration to 3 weeks post intranasal intervention. ]
    PedsQL-SCD Module scores obtained by study clinicians using over-the-phone interviews between two-three weeks post intervention will be a secondary outcome measure.

  3. Analgesia use - paracetamol [ Time Frame: Time of initial intranasal drug administration to 2 hours post intranasal drug administration ]
    Individual evaluation of total paracetamol use per kilogram body weight

  4. Analgesia use - ibuprofen [ Time Frame: Time of initial intranasal drug administration to 2 hours post intranasal drug administration ]
    Individual evaluation of total ibuprofen use per kilogram body weight

  5. Analgesia use - opioids [ Time Frame: Time of initial intranasal drug administration to 2 hours post intranasal drug administration ]
    Individual evaluation of total opioid use expressed as morphine equivalents per body weight.


Other Outcome Measures:
  1. Adverse Events [ Time Frame: Time of initial intranasal drug administration to 2 hours post intranasal drug administration ]
    Adverse events include: bad taste is mouth, drowsiness, dizziness, itchy nose, nausea, dysphoria, and other novel subjective negative experiences

  2. Serious Adverse Events [ Time Frame: Time of initial intranasal drug administration to 2 hours post intranasal drug administration ]
    Serious adverse events include: apnea, assisted ventilation, bradypnea, cyanosis, dissociation, emergence reaction, hypotension, laryngospasm, myoclonus, seizure, and vomiting



Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Sickle cell disease (SCD)
  • Vasoocclusive pain crisis
  • Requiring analgesia

Exclusion Criteria:

  • Anatomic variations of nose precluding intranasal medication administration
  • Ketamine allergy
  • Non-verbal
  • Obtunded
  • Pregnant
  • Other acute SCD complications:

    • Acute chest syndrome
    • Sepsis
    • Stroke
    • Splenic sequestration
    • Pulmonary embolism
    • Acute osteomyelitis

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): NCT02573714


Contacts
Contact: James R Young, MD 704-578-5078 james.young@carolinashealthcare.org

Locations
Cameroon
Mbingo Baptist Hospital Recruiting
Bamenda, Northwest Province, Cameroon
Contact: James R Young, MD    704-578-5078    james.young@carolinashealthcare.org   
Contact: Ernest Nshom, MD         
Sub-Investigator: Ethan Helm, MD         
Principal Investigator: Ernest Nshom, MD         
Tanzania
Muhimbili National Hospital Not yet recruiting
Dar es Salam, Tanzania
Contact: Hendry R Sawe, MD       Hendry_sawe@yahoo.com   
Contact: Juma Mfinanga, MD       jumamfinanga@gmail.com   
Principal Investigator: Hendry R Sawe, MD         
Sub-Investigator: Juma Mfinanga, MD         
Sponsors and Collaborators
Cameroon Baptist Convention Health
Carolinas Medical Center
Muhimbili National Hospital
Investigators
Study Director: Ernest Nshom, MD Cameroon Baptist Convention Health
Study Chair: Michael Runyon, MD Carolinas Medical Center
Principal Investigator: James R Young, MD Carolinas Medical Center
Study Director: Stacy Reynolds, MD Carolinas Medical Center
Study Director: Hendry R Sawe, MD Muhimbili University of Health and Allied Sciences
Study Director: Juma Mfinanga, MD Mihumbili National Hospital

Publications:
Walker SE, Law S, DeAngelis C. Stability and compatibility of hydromorphone and ketamine in normal saline. Can J Hosp Pharm. 2001;54(3):191-199.
PedsQL Sickle Cell Disease Module, Version 3.0. 1998 JW Varni, Ph.D. (http://www.proqolid.org/instruments/pediatric_quality_of_life_inventory_sickle_cell_disease_module_pedsql_sickle_cell_disease_module)
Chien YW, Su KSE, Chang SF, Chapter 1: Anatomy and Physiology of the Nose. Nasal Systemic Drug Delivery, 1989. Dekker, New York: p. 1-26.
Who.int,. "WHO | WHO Model Lists Of Essential Medicines." N.p., 2015. Web. 20 July 2015.
American Pain Society (1999a) Guideline for the Management of Acute and Chronic Pain in Sickle Cell Disease. American Pain Society, Glenview, IL.
World Health Organisation, "Sickle cell anaemia. Agenda item 11.4," in 59th World Health Assembly, 27 May 2006, World Health Organisation, Geneva, Switzerland, 2006.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cameroon Baptist Convention Health
ClinicalTrials.gov Identifier: NCT02573714     History of Changes
Other Study ID Numbers: IRB2015-07
MNH/IRB/I/2015/14 ( Other Identifier: Muhimbili National Hospital IRB )
TFDA0015/CTR/0015/9 ( Other Identifier: Tanzania Food and Drugs Authority )
NIMR/HQ/R.8a/Vol. IX/2299 ( Other Identifier: Tanzania National Institute for Medical Research )
First Posted: October 12, 2015    Key Record Dates
Last Update Posted: January 29, 2018
Last Verified: January 2018

Keywords provided by Cameroon Baptist Convention Health:
Ketamine
Intranasal
Pain crisis
Vasoocclusive Pain
Sickle cell disease

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Ketamine
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