Pain Management in Children and Young Adults With Sickle Cell Disease

• ClinicalTrials.gov Identifier: NCT01954927
• Recruitment Status: Completed
• First Posted: October 7, 2013
• Results First Posted: April 2, 2019
• Last Update Posted: April 2, 2019
• Sponsor: St. Jude Children's Research Hospital
• Collaborator: Scan | Design Foundation
• Information provided by (Responsible Party): St. Jude Children's Research Hospital

Tracking Information

• First Submitted Date: September 27, 2013
• First Posted Date: October 7, 2013
• Results First Submitted Date: January 3, 2019
• Results First Posted Date: April 2, 2019
• Last Update Posted Date: April 2, 2019
• Actual Study Start Date: October 7, 2013
• Actual Primary Completion Date: January 3, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 11, 2019)

Number of Participants With Successful Pain Interventions by Arm Between Presentation and 3 Hours Post Administration of Study Drug [ Time Frame: 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. ]

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.

Original Primary Outcome Measures (submitted: September 27, 2013)

Number and proportion of participants with successful pain interventions by arm [ Time Frame: Baseline and 3 hours post administration of study drug ]

Pain scales used are the numerical rating system, the Faces Pain Scale, and the 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.

Current Secondary Outcome Measures (submitted: March 11, 2019)

Morphine Equivalent Doses Administered From Presentation to 3-hours Post Treatment With Gabapentin/Placebo [ Time Frame: 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. ]

The equivalent dose of morphine in mg

Original Secondary Outcome Measures (submitted: September 27, 2013)

Total dose (mg) of opioid analgesic administered [ Time Frame: All doses given between baseline and 3 hours post administration of study drug ]

Summary statistics of the total morphine dose or morphine equivalent (mg/kg) used to control pain during VOC between presentation to the acute care setting and 3 hours post administration of study drug, in the gabapentin and placebo groups will be provided. Test of normality such as Shapiro-Wilk test will be applied to the total morphine dose or morphine equivalent (mg/kg) to examine their deviation from the normal distribution. A two-sample t-test or Wilcoxon rank sum test will be used to compare the total morphine dose or morphine equivalent (mg/kg) for the gabapentin vs. placebo groups depending on whether the normality assumption of the data holds.

Current Other Pre-specified Outcome Measures (submitted: March 11, 2019)

• Number of Participants With Successful Pain Interventions by Arm Between Presentation and Point of Decision for Either Hospital Admission or Discharge to Home [ Time Frame: From time of presentation to the acute care setting until time of either discharge to home or admission to the hospital, up to 8 hours. ]
  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 Point of decision for either hospital admission or discharge to home is 33% or greater, then this patient will be defined as having a successful intervention.
• Morphine Equivalent Doses Administered From Presentation to the Point of Decision for Either Admission or Discharge to Home [ Time Frame: From time of presentation to the acute care setting until time of either discharge to home or admission to the hospital, up to 8 hours. ]
  To compare the total morphine equivalent dose (mg/kg) used to control pain during VOC between presentation to the acute care setting and the point of decision for either admission or discharge to home, in the gabapentin and placebo groups.
• Hospital Admission [ Time Frame: From time of presentation to the acute care setting until time of either discharge to home or admission to the hospital, up to 8 hours. ]
  To compare the rate of admission related to pain management, in the gabapentin vs. placebo groups. (Outcome: binary response - admitted or discharged)
• Absolute Change in Pain From Study Drug to 3 Hours Post Administration of Study Drug [ Time Frame: Study drug administration to 3-hours post study drug administration ]
  To compare the change in pain score from time of administration of study drug to assessment at 3 hours post administration of study drug in the gabapentin vs. placebo groups. (0=no pain and 10=worst possible pain)
• Absolute Change in Pain, Study Drug to Hospital Discharge Decision [ Time Frame: From time of presentation to the acute care setting until time of either discharge to home or admission to the hospital, up to 8 hours. ]
  To compare the change in pain score from time of administration of study drug to the point of decision for either admission or discharge to home, in the gabapentin and placebo groups. (0=no pain and 10=worst possible pain)

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Sickle Cell Disease

Intervention

• Drug: Gabapentin
  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.
  Other Name: Neurontin(R)
• Drug: Placebo
  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.

Study Arms

• Active Comparator: Gabapentin
  Patients will be randomized to receive one dose of gabapentin.
  Intervention: Drug: Gabapentin
• Placebo Comparator: Placebo
  Patients will be randomized to receive one dose of placebo.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 4, 2018): 90
• Original Estimated Enrollment (submitted: September 27, 2013): 190
• Actual Study Completion Date: January 3, 2018
• Actual Primary Completion Date: January 3, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 20 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01954927
• Other Study ID Numbers: PMVOC
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: St. Jude Children's Research Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: St. Jude Children's Research Hospital
• Original Study Sponsor: Same as current
• Collaborators: Scan | Design Foundation

Investigators

• Principal Investigator: Doralina Anghelescu, MD; St. Jude Children's Research Hospital

• PRS Account: St. Jude Children's Research Hospital
• Verification Date: July 2018