Pain Management in Children and Young Adults With Sickle Cell Disease

Study Overview
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Brief Summary
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This is a phase II double-blind placebo-controlled clinical trial evaluating the effect of gabapentin when added to standard pain management for patients with sickle cell disease experiencing acute pain crisis in the ambulatory care setting. Sickle cell pain is different for every patient. Some patients get complete relief from routine pain medicines, and others need more time or more doses of pain medicines before the pain goes away completely. It is known that humans have many types of pain, including something called neuropathic pain. Neuropathic pain in other conditions (such as diabetes) has been treated successfully with a medicine called gabapentin. The investigators in this study suspect that some sickle cell pain is a combination of pain types. They would like to see if adding gabapentin to the usual pain medicines makes pain go away faster or more completely. Primary Objective: To assess the analgesic efficacy of gabapentin vs. placebo for pain during vaso-occlusive crisis (VOC) in participants with sickle cell disease (SCD). A response to study drug will be defined by a decrease in pain score of ≥ 33% between presentation to the acute care setting and assessment at 3 hours post administration of study drug. Secondary Objective: To compare the total morphine equivalent dose (mg/kg) used to control pain during VOC between presentation to the acute care setting and assessment at 3 hours post administration of study drug in the gabapentin vs. placebo groups.

Detailed Description
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Upon participant enrollment, study staff will randomize the participant to one of 2 possible treatment arms: a single dose of gabapentin or a single dose of placebo. Morphine or other opioid and non-steroidal anti-inflammatory drugs will be available to both groups as needed for pain and will be administered according to the current standard of care for pain in VOC from the Department of Hematology at St. Jude Children's Research Hospital (SJCRH). Randomization will be performed in the SJCRH pharmacy by a pharmacist. The randomization will be stratified by three age categories (1-3 years of age, 4-6 years, and 7 years or older) for which distinct pain assessment tools are applied and for 2 pain score categories at assessment at presentation (4-6 and 7-10, respectively). A block randomization with block sizes varying randomly between 4 and 6 will be used in each stratum. Pain scores will be obtained at presentation to the acute care setting and 3 hours (± 15 minutes) post administration of study drug. Participants who were discharged will be contacted by study staff between 24 and 72 hours following administration of study drug to see if there have been any side effects. Patients who were admitted after administration of the study drug will be monitored through hospital record to determine if any unexpected events occurred. After this follow up, participation in the study is complete.

Official Title
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Pain Management of Vaso-Occlusive Crisis in Children and Young Adults With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Gabapentin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have sickle cell disease (any genotype) documented in the St. Jude medical record. Participant must be seeking care for acute vaso-occlusive pain at St. Jude Children's Research Hospital. Participant age must be ≥1 year and <21 years. Exclusion Criteria: Prior randomization in this study. Mild pain (score <4) or pain for which treatment with opioid is not indicated. Pregnant or lactating female. Decreased glomerular filtration rate (GFT) (<60ml/min/1.73m^2) as estimated by the revised Schwartz equation. Current treatment with gabapentinoid drugs (gabapentin or pregabalin). Known seizure disorder. Current treatment with antiepileptic agents. Pain in combination with other clinical symptoms that require additional interventions, including fever with focus, acute chest syndrome, acute injury, or splenic sequestration. Allergy to gabapentin. Current participation in another research study with an investigational new drug/device (IND/IDE) agent. Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 20 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gabapentin<br>Patients will be randomized to receive one dose of gabapentin. | Drug: Gabapentin<br>* Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm will receive a single dose of gabapentin as soon after enrollment as feasible. The gabapentin dose will be given orally and will be approximately 15 mg/kg with a maximum dose of 900 mg.<br>* Other names: Neurontin(R);|
| Placebo Comparator: Placebo<br>Patients will be randomized to receive one dose of placebo. | Drug: Placebo<br>* Placebo will be prepared by the SJCRH pharmacy and will be similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm will receive a single dose of placebo as soon after enrollment as feasible. The placebo dose will be given orally and will be approximately 15 mg/kg with a maximum dose of 900mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Successful Pain Interventions by Arm Between Presentation and 3 Hours Post Administration of Study Drug | Pain scales used are the numerical rating system, the Faces Pain Scale, and the Faces, Legs, Arms, Cry and Consolability (FLACC) pain scale (for patients 7 years or older, ages 4-6 years, or less than 4 years, respectively). For each patient, if the reduction of the pain scores (0=no pain and 10=worst possible pain) between presentation to the acute care setting and 3 hours post administration of study drug is 33% or greater, then this patient will be defined as having a successful intervention. The proportions of successful interventions in the gabapentin and placebo groups will be estimated and compared using Z-test. | Baseline and 3 hours (±30 minutes) post administration of study drug. The 3-hour pain assessment time-period was extended for subjects that were sleep until the first available measurement. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morphine Equivalent Doses Administered From Presentation to 3-hours Post Treatment With Gabapentin/Placebo | The equivalent dose of morphine in mg | The 3-hour pain assessment was the pain assessment closest in time to the 3-hour time and was typically within 30 minutes of target. The time period was extended for 12 patients that were sleeping. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain control