Trial Outcomes & Findings for Pain Management in Children and Young Adults With Sickle Cell Disease (NCT NCT01954927)

NCT ID: NCT01954927

Last Updated: 2019-04-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

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.

Results posted on

2019-04-02

Participant Flow

Participants meeting eligibility criteria were enrolled between 10/7/2013 to 1/3/2018. They were randomized to either gabapentin or placebo.

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.

Participant milestones

Participant milestones
Measure	Gabapentin 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).	Placebo 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 Study STARTED	45	45
Overall Study COMPLETED	42	44
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Gabapentin 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).	Placebo 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 Study Withdrawal by Subject	3	1

Baseline Characteristics

Pain Management in Children and Young Adults With Sickle Cell Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gabapentin n=42 Participants 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).	Placebo n=44 Participants 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 n=86 Participants Total of all reporting groups
Age, Categorical <=18 years	39 Participants n=5 Participants	42 Participants n=7 Participants	81 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	11.8 years STANDARD_DEVIATION 4.5 • n=5 Participants	11.8 years STANDARD_DEVIATION 5.3 • n=7 Participants	11.8 years STANDARD_DEVIATION 4.9 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	22 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	22 Participants n=7 Participants	51 Participants n=5 Participants
Race/Ethnicity, Customized Black	42 Participants n=5 Participants	44 Participants n=7 Participants	86 Participants n=5 Participants
Race/Ethnicity, Customized Non-Spanish speaking Non Hispanic	40 Participants n=5 Participants	44 Participants n=7 Participants	84 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	42 participants n=5 Participants	44 participants n=7 Participants	86 participants n=5 Participants
Sickle cell genotype SBeta Zero Thalassemia	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Sickle cell genotype Hemoglobin SC	10 Participants n=5 Participants	15 Participants n=7 Participants	25 Participants n=5 Participants
Sickle cell genotype Hemoglobin SS	18 Participants n=5 Participants	26 Participants n=7 Participants	44 Participants n=5 Participants
Sickle cell genotype Other	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
Pain score category at presentation 4-6	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Pain score category at presentation 7-10	32 Participants n=5 Participants	32 Participants n=7 Participants	64 Participants n=5 Participants
Pain at presentation (before randomization)	8.0 units on a scale n=5 Participants	8.0 units on a scale n=7 Participants	8.0 units on a scale n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: 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.

Outcome measures

Outcome measures
Measure	Gabapentin n=40 Participants 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.	Placebo n=42 Participants 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.
Number of Participants With Successful Pain Interventions by Arm Between Presentation and 3 Hours Post Administration of Study Drug No	13 Participants	17 Participants
Number of Participants With Successful Pain Interventions by Arm Between Presentation and 3 Hours Post Administration of Study Drug Yes	27 Participants	25 Participants

SECONDARY outcome

Timeframe: 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.

Population: 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.

The equivalent dose of morphine in mg

Outcome measures

Outcome measures
Measure	Gabapentin n=42 Participants 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.	Placebo n=44 Participants 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.
Morphine Equivalent Doses Administered From Presentation to 3-hours Post Treatment With Gabapentin/Placebo	0.12 mg/kg Interval 0.09 to 0.22	0.13 mg/kg Interval 0.09 to 0.22

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gabapentin n=40 Participants 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.	Placebo n=44 Participants 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.
Number of Participants With Successful Pain Interventions by Arm Between Presentation and Point of Decision for Either Hospital Admission or Discharge to Home No	10 Participants	17 Participants
Number of Participants With Successful Pain Interventions by Arm Between Presentation and Point of Decision for Either Hospital Admission or Discharge to Home Yes	30 Participants	27 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gabapentin n=42 Participants 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.	Placebo n=44 Participants 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.
Morphine Equivalent Doses Administered From Presentation to the Point of Decision for Either Admission or Discharge to Home	0.13 mg/kg Interval 0.1 to 0.25	0.13 mg/kg Interval 0.09 to 0.25

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Population: 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.

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

Outcome measures

Outcome measures
Measure	Gabapentin n=42 Participants 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.	Placebo n=44 Participants 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.
Hospital Admission No	32 Participants	32 Participants
Hospital Admission Yes	10 Participants	12 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Study drug administration to 3-hours post study drug administration

Population: 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.

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)

Outcome measures

Outcome measures
Measure	Gabapentin n=35 Participants 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.	Placebo n=36 Participants 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.
Absolute Change in Pain From Study Drug to 3 Hours Post Administration of Study Drug	0 score on a scale Interval 0.0 to 2.0	0.5 score on a scale Interval 0.0 to 2.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Population: 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.

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)

Outcome measures

Outcome measures
Measure	Gabapentin n=35 Participants 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.	Placebo n=38 Participants 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.
Absolute Change in Pain, Study Drug to Hospital Discharge Decision	1.0 score on a scale Interval 0.0 to 3.0	0.5 score on a scale Interval 0.0 to 2.0

Adverse Events

Gabapentin

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Gabapentin n=42 participants at risk 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.	Placebo n=44 participants at risk 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.
Nervous system disorders Dizziness	2.4% 1/42 • Number of events 1 • Adverse events were evaluated by one phone contact within the following 72 hours.	0.00% 0/44 • Adverse events were evaluated by one phone contact within the following 72 hours.
General disorders Fatigue	2.4% 1/42 • Number of events 1 • Adverse events were evaluated by one phone contact within the following 72 hours.	0.00% 0/44 • Adverse events were evaluated by one phone contact within the following 72 hours.
General disorders Headache	2.4% 1/42 • Number of events 1 • Adverse events were evaluated by one phone contact within the following 72 hours.	0.00% 0/44 • Adverse events were evaluated by one phone contact within the following 72 hours.
Skin and subcutaneous tissue disorders Pruritus	2.4% 1/42 • Number of events 1 • Adverse events were evaluated by one phone contact within the following 72 hours.	0.00% 0/44 • Adverse events were evaluated by one phone contact within the following 72 hours.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.4% 1/42 • Number of events 1 • Adverse events were evaluated by one phone contact within the following 72 hours.	2.3% 1/44 • Number of events 1 • Adverse events were evaluated by one phone contact within the following 72 hours.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	2.4% 1/42 • Number of events 1 • Adverse events were evaluated by one phone contact within the following 72 hours.	0.00% 0/44 • Adverse events were evaluated by one phone contact within the following 72 hours.
Gastrointestinal disorders Vomiting	4.8% 2/42 • Number of events 2 • Adverse events were evaluated by one phone contact within the following 72 hours.	2.3% 1/44 • Number of events 1 • Adverse events were evaluated by one phone contact within the following 72 hours.

Additional Information

Doralina Anghelescu, MD

St. Jude Children's Research Hospital

Phone: (901) 595-4034

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place