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

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Sickle Cell Disease
• Interventions: Drug: Gabapentin; Drug: Placebo
• Enrollment: 90

Participant Flow

Recruitment Details	Participants meeting eligibility criteria were enrolled between 10/7/2013 to 1/3/2018. They were randomized to either gabapentin or placebo.
Pre-assignment Details	The study was stopped early due to slow accrual when there were 82 patients with evaluable pain assessments available for the primary objective. Patients asleep at pain assessment times led to missing pain assessments.

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	Participants were randomized to receive one dose of gabapentin. Gabapentin: Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm received a single dose of gabapentin as soon after enrollment as feasible, given orally, approximately 15 milligram/kilogram (mg/kg) with a maximum dose of 900 milligram (mg).	Participants were randomized to receive one dose of placebo. Placebo: Placebo was prepared by the SJCRH pharmacy, similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm received a single dose of placebo as soon after enrollment as feasible, given orally, in a volume that matched the active medication arm.
Period Title: Overall Study
Started	45	45
Completed	42	44
Not Completed	3	1
Reason Not Completed
Withdrawal by Subject	3	1

Baseline Characteristics

Arm/Group Title		Gabapentin	Placebo	Total
Arm/Group Description		Participants were randomized to receive one dose of gabapentin. Gabapentin: Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm received a single dose of gabapentin as soon after enrollment as feasible, given orally, approximately 15 milligram/kilogram (mg/kg) with a maximum dose of 900 milligram (mg).	Participants were randomized to receive one dose of placebo. Placebo: Placebo was prepared by the SJCRH pharmacy, similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm received a single dose of placebo as soon after enrollment as feasible, given orally, in a volume that matched the active medication arm.	Total of all reporting groups
Overall Number of Baseline Participants		42	44	86
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants	44 participants	86 participants
	<=18 years	39 92.9%	42 95.5%	81 94.2%
	Between 18 and 65 years	3 7.1%	2 4.5%	5 5.8%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	42 participants	44 participants	86 participants
		11.9; (8.2 to 15.6)	14.3; (7.7 to 16.3)	12.4; (8.1 to 15.8)
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	42 participants	44 participants	86 participants
		11.8 (4.5)	11.8 (5.3)	11.8 (4.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants	44 participants	86 participants
	Female	13 31.0%	22 50.0%	35 40.7%
	Male	29 69.0%	22 50.0%	51 59.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	42 participants	44 participants	86 participants
Black		42 100.0%	44 100.0%	86 100.0%
Non-Spanish speaking Non Hispanic		40 95.2%	44 100.0%	84 97.7%
Unknown		2 4.8%	0 0.0%	2 2.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	42 participants	44 participants	86 participants
		42	44	86
Sickle cell genotype; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	42 participants	44 participants	86 participants
SBeta Zero Thalassemia		6 14.3%	2 4.5%	8 9.3%
Hemoglobin SC		10 23.8%	15 34.1%	25 29.1%
Hemoglobin SS		18 42.9%	26 59.1%	44 51.2%
Other		8 19.0%	1 2.3%	9 10.5%
Pain score category at presentation [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	42 participants	44 participants	86 participants
4-6		10 23.8%	12 27.3%	22 25.6%
7-10		32 76.2%	32 72.7%	64 74.4%
		[1] Measure Description: (0=no pain and 10=worst possible pain)
Pain at presentation (before randomization) [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	42 participants	44 participants	86 participants
		8.0 (1.6)	7.7 (1.9)	7.8 (1.8)
		[1] Measure Description: (0=no pain and 10=worst possible pain)
Pain at presentation (before randomization) [1]; Median (Inter-Quartile Range); Unit of measure: Units on a scale
	Number Analyzed	42 participants	44 participants	86 participants
		8.0; (7.0 to 10.0)	8.0; (6.5 to 10.0)	8.0; (7.0 to 10.0)
		[1] Measure Description: (0=no pain and 10=worst possible pain)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Successful Pain Interventions by Arm Between Presentation and 3 Hours Post Administration of Study Drug
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Patients with Sickle cell disease (any genotype) ages ≥1 year and <21 years seeking care for acute vaso-occlusive pain at St Jude Children's Hospital. A total of 4 subjects were missing the pain assessment at 3 hours (2 in each arm). The resulting sample sizes were n=40 (Gabapentin arm) and n=42 (placebo arm), for a total sample size of n=82.

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description:	Participants were randomized to receive one dose of gabapentin. Gabapentin: Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm received a single dose of gabapentin as soon after enrollment as feasible, given orally, approximately 15 mg/kg with a maximum dose of 900 mg.	Participants were randomized to receive one dose of placebo. Placebo: Placebo was prepared by the SJCRH pharmacy, similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm received a single dose of placebo as soon after enrollment as feasible, given orally, in a volume that matched the active medication arm.
Overall Number of Participants Analyzed	40	42
Measure Type: Count of Participants; Unit of Measure: Participants
No	13 32.5%	17 40.5%
Yes	27 67.5%	25 59.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.227
	Comments	1-sided p-value
	Method	z-test Proportion
	Comments	z-test of proportions without continuity correction

2. Secondary Outcome

Title	Morphine Equivalent Doses Administered From Presentation to 3-hours Post Treatment With Gabapentin/Placebo
Description	The equivalent dose of morphine in mg
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.

Outcome Measure Data

Analysis Population Description

Patients with Sickle cell disease (any genotype) ages ≥1 year and <21 years seeking care for acute vaso-occlusive pain at St Jude Children's Hospital.

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description:	Participants were randomized to receive one dose of gabapentin. Gabapentin: Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm received a single dose of gabapentin as soon after enrollment as feasible, given orally, approximately 15 mg/kg with a maximum dose of 900 mg.	Participants were randomized to receive one dose of placebo. Placebo: Placebo was prepared by the SJCRH pharmacy, similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm received a single dose of placebo as soon after enrollment as feasible, given orally, in a volume that matched the active medication arm.
Overall Number of Participants Analyzed	42	44
Median (Inter-Quartile Range); Unit of Measure: mg/kg
	0.12; (0.09 to 0.22)	0.13; (0.09 to 0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.897
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

3. Other Pre-specified Outcome

Title	Number of Participants With Successful Pain Interventions by Arm Between Presentation and Point of Decision for Either Hospital Admission or Discharge to Home
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Patients with Sickle cell disease (any genotype) ages ≥1 year and <21 years seeking care for acute vaso-occlusive pain at St Jude Children's Hospital. There were 2 subjects in the Gabapentin group that did not have a pain assessment admit/discharge decision. N=84 patients had assessments at both presentation and admit/discharge.

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description:	Participants were randomized to receive one dose of gabapentin. Gabapentin: Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm received a single dose of gabapentin as soon after enrollment as feasible, given orally, approximately 15 mg/kg with a maximum dose of 900 mg.	Participants were randomized to receive one dose of placebo. Placebo: Placebo was prepared by the SJCRH pharmacy, similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm received a single dose of placebo as soon after enrollment as feasible, given orally, in a volume that matched the active medication arm.
Overall Number of Participants Analyzed	40	44
Measure Type: Count of Participants; Unit of Measure: Participants
No	10 25.0%	17 38.6%
Yes	30 75.0%	27 61.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.181
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

4. Other Pre-specified Outcome

Title	Morphine Equivalent Doses Administered From Presentation to the Point of Decision for Either Admission or Discharge to Home
Description	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.
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.

Outcome Measure Data

Analysis Population Description

Patients with Sickle cell disease (any genotype) ages ≥1 year and <21 years seeking care for acute vaso-occlusive pain at St Jude Children's Hospital.

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description:	Participants were randomized to receive one dose of gabapentin. Gabapentin: Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm received a single dose of gabapentin as soon after enrollment as feasible, given orally, approximately 15 mg/kg with a maximum dose of 900 mg.	Participants were randomized to receive one dose of placebo. Placebo: Placebo was prepared by the SJCRH pharmacy, similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm received a single dose of placebo as soon after enrollment as feasible, given orally, in a volume that matched the active medication arm.
Overall Number of Participants Analyzed	42	44
Median (Inter-Quartile Range); Unit of Measure: mg/kg
	0.13; (0.10 to 0.25)	0.13; (0.09 to 0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.730
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

5. Other Pre-specified Outcome

Title	Hospital Admission
Description	To compare the rate of admission related to pain management, in the gabapentin vs. placebo groups. (Outcome: binary response - admitted or discharged)
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.

Outcome Measure Data

Analysis Population Description

Patients with Sickle cell disease (any genotype) ages ≥1 year and <21 years seeking care for acute vaso-occlusive pain at St Jude Children's Hospital.

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description:	Participants were randomized to receive one dose of gabapentin. Gabapentin: Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm received a single dose of gabapentin as soon after enrollment as feasible, given orally, approximately 15 mg/kg with a maximum dose of 900 mg.	Participants were randomized to receive one dose of placebo. Placebo: Placebo was prepared by the SJCRH pharmacy, similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm received a single dose of placebo as soon after enrollment as feasible, given orally, in a volume that matched the active medication arm.
Overall Number of Participants Analyzed	42	44
Measure Type: Count of Participants; Unit of Measure: Participants
No	32 76.2%	32 72.7%
Yes	10 23.8%	12 27.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.713
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

6. Other Pre-specified Outcome

Title	Absolute Change in Pain From Study Drug to 3 Hours Post Administration of Study Drug
Description	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)
Time Frame	Study drug administration to 3-hours post study drug administration

Outcome Measure Data

Analysis Population Description

Patients with Sickle cell disease (any genotype) ages ≥1 year and <21 years seeking care for acute vaso-occlusive pain at St Jude Children's Hospital. Placebo arm: 6 subjects missed pain assessments at treatment; 2 missed pain assessment at 3h. Gabapentin arm: 7 missed pain assessment at treatment; 2 of the 7 also missed the assessment at 3h.

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description:	Participants were randomized to receive one dose of gabapentin. Gabapentin: Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm received a single dose of gabapentin as soon after enrollment as feasible, given orally, approximately 15 mg/kg with a maximum dose of 900 mg.	Participants were randomized to receive one dose of placebo. Placebo: Placebo was prepared by the SJCRH pharmacy, similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm received a single dose of placebo as soon after enrollment as feasible, given orally, in a volume that matched the active medication arm.
Overall Number of Participants Analyzed	35	36
Median (Inter-Quartile Range); Unit of Measure: score on a scale
	0; (0 to 2)	0.5; (0 to 2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.739
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

7. Other Pre-specified Outcome

Title	Absolute Change in Pain, Study Drug to Hospital Discharge Decision
Description	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)
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.

Outcome Measure Data

Analysis Population Description

Patients with Sickle cell disease (any genotype) ages ≥1 year and <21 years seeking care for acute vaso-occlusive pain at St Jude Children's Hospital. Placebo arm: 6 subjects missed pain assessments at treatment. Gabapentin arm: 7 subjects missed pain assessment at treatment; 2 of the 7 missed the assessment at hospital discharge decision.

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description:	Participants were randomized to receive one dose of gabapentin. Gabapentin: Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm received a single dose of gabapentin as soon after enrollment as feasible, given orally, approximately 15 mg/kg with a maximum dose of 900 mg.	Participants were randomized to receive one dose of placebo. Placebo: Placebo was prepared by the SJCRH pharmacy, similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm received a single dose of placebo as soon after enrollment as feasible, given orally, in a volume that matched the active medication arm.
Overall Number of Participants Analyzed	35	38
Median (Inter-Quartile Range); Unit of Measure: score on a scale
	1.0; (0.0 to 3.0)	0.5; (0.0 to 2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.388
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Adverse Events

Time Frame	Adverse events were evaluated by one phone contact within the following 72 hours.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Gabapentin		Placebo
Arm/Group Description	Participants were randomized to receive one dose of gabapentin. Gabapentin: Gabapentin is supplied as an oral suspension. Patients randomized to the gabapentin arm received a single dose of gabapentin as soon after enrollment as feasible, given orally, approximately 15 mg/kg with a maximum dose of 900 mg.		Participants were randomized to receive one dose of placebo. Placebo: Placebo was prepared by the SJCRH pharmacy, similar in appearance, quantity and taste to the gabapentin drug. Patients randomized to the placebo arm received a single dose of placebo as soon after enrollment as feasible, given orally, in a volume that matched the active medication arm.
All-Cause Mortality
	Gabapentin		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/42 (0.00%)		0/44 (0.00%)
Serious Adverse Events
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0.00%)		0/44 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/42 (11.90%)		2/44 (4.55%)
Gastrointestinal disorders
Vomiting *	2/42 (4.76%)	2	1/44 (2.27%)	1
General disorders
Fatigue *	1/42 (2.38%)	1	0/44 (0.00%)	0
Headache *	1/42 (2.38%)	1	0/44 (0.00%)	0
Nervous system disorders
Dizziness *	1/42 (2.38%)	1	0/44 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonitis *	1/42 (2.38%)	1	1/44 (2.27%)	1
Respiratory, thoracic and mediastinal disorders - Other *	1/42 (2.38%)	1	0/44 (0.00%)	0
Skin and subcutaneous tissue disorders
Pruritus *	1/42 (2.38%)	1	0/44 (0.00%)	0
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Doralina Anghelescu, MD
• Organization: St. Jude Children's Research Hospital
• Phone: (901) 595-4034
• EMail: doralina.anghelescu@stjude.org

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT01954927
• Other Study ID Numbers: PMVOC
• First Submitted: September 27, 2013
• First Posted: October 7, 2013
• Results First Submitted: January 3, 2019
• Results First Posted: April 2, 2019
• Last Update Posted: April 2, 2019