Sub-dissociative Intranasal Ketamine for Pediatric Sickle Cell Pain Crises

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Ketamine
* Drug: Normal Saline
* Other: Standard Pain Therapy
* Other: Pediatric Quality of Life - Sickle Cell Disease Module
* Other: Faces Pain Scale - Revised


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 16 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intranasal Ketamine<br>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<br>* 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.<br>Other: Standard Pain Therapy<br>* Typical management strategy for pediatric sickle cell disease vasoocclusive crises including acetaminophen/paracetamol, ibuprofen, oral opioids, and injectable opioids depending on pain severity.<br>Other: Pediatric Quality of Life - Sickle Cell Disease Module<br>* 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.<br>* Other names: PedsQL-SCD;Other: Faces Pain Scale - Revised<br>* 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.<br>* Other names: FPS-R;|
| Placebo Comparator: Normal Saline<br>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<br>* 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.<br>* Other names: NaCl 0.9%;Other: Standard Pain Therapy<br>* Typical management strategy for pediatric sickle cell disease vasoocclusive crises including acetaminophen/paracetamol, ibuprofen, oral opioids, and injectable opioids depending on pain severity.<br>Other: Pediatric Quality of Life - Sickle Cell Disease Module<br>* 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.<br>* Other names: PedsQL-SCD;Other: Faces Pain Scale - Revised<br>* 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.<br>* Other names: FPS-R;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital length of stay | Hospital length of stay recorded from time zero to time of discharge documented by the study clinician will be a secondary outcome measure. | through study completion, an average of 3 days | 
| Quality of life assessment (PedsQL-SCD Module scores) | 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. | Time of first intranasal administration to 3 weeks post intranasal intervention. | 
| Analgesia use - paracetamol | Individual evaluation of total paracetamol use per kilogram body weight | Time of initial intranasal drug administration to 2 hours post intranasal drug administration | 
| Analgesia use - ibuprofen | Individual evaluation of total ibuprofen use per kilogram body weight | Time of initial intranasal drug administration to 2 hours post intranasal drug administration | 
| Analgesia use - opioids | Individual evaluation of total opioid use expressed as morphine equivalents per body weight. | Time of initial intranasal drug administration to 2 hours post intranasal drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine, Intranasal, Pain crisis, Vasoocclusive Pain, Sickle cell disease