NCT01954927

Pain Management in Children and Young Adults With Sickle Cell Disease

Completed Phase 2 Results posted Last updated 2 April 2019

What this trial tests

Phase 2 trial testing Gabapentin in Sickle Cell Disease in 90 participants. Completed in 3 January 2018.

Timeline

7 October 2013

Primary endpoint
3 January 2018

3 January 2018

Quick facts

Lead sponsor	St. Jude Children's Research Hospital
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	90
Start date	7 October 2013
Primary completion	3 January 2018
Estimated completion	3 January 2018
Sites	1 location across United States

Drugs / interventions tested

• Gabapentin (Gabapentin) — full drug profile →
• Placebo

Conditions studied

• Sickle Cell Disease — all drugs for Sickle Cell Disease →

Sponsor

St. Jude Children's Research Hospital

Who can join

Adults 1 to 20, any sex, with Sickle Cell Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Successful Pain Interventions by Arm Between Presentation and 3 Hours Post Administration of Study Drug Primary · 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

No

Group	Value	95% CI
Gabapentin	13
Placebo	17

Yes

Group	Value	95% CI
Gabapentin	27
Placebo	25

Morphine Equivalent Doses Administered From Presentation to 3-hours Post Treatment With Gabapentin/Placebo Secondary · 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

Group	Value	95% CI
Gabapentin	0.12	0.09 – 0.22
Placebo	0.13	0.09 – 0.22

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

No

Group	Value	95% CI
Gabapentin	10
Placebo	17

Yes

Group	Value	95% CI
Gabapentin	30
Placebo	27

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

Group	Value	95% CI
Gabapentin	0.13	0.10 – 0.25
Placebo	0.13	0.09 – 0.25

Hospital Admission Secondary · 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)

No

Group	Value	95% CI
Gabapentin	32
Placebo	32

Yes

Group	Value	95% CI
Gabapentin	10
Placebo	12

Absolute Change in Pain From Study Drug to 3 Hours Post Administration of Study Drug Secondary · 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)

Group	Value	95% CI
Gabapentin	0	0 – 2
Placebo	0.5	0 – 2

Absolute Change in Pain, Study Drug to Hospital Discharge Decision Secondary · 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)

Group	Value	95% CI
Gabapentin	1.0	0.0 – 3.0
Placebo	0.5	0.0 – 2.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were evaluated by one phone contact within the following 72 hours.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Gabapentin

Serious: 0/42 (0%)

Deaths: 0/42

Placebo

Serious: 0/44 (0%)

Deaths: 0/44

Other adverse events (7 terms — click to expand)

Reaction	System	Gabapentin	Placebo
Vomiting	Gastrointestinal disorders	—	—
Dizziness	Nervous system disorders	—	—
Fatigue	General disorders	—	—
Headache	General disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory, thoracic and mediastinal disorders - Other	Respiratory, thoracic and mediastinal disorders	—	—

Data from ClinicalTrials.gov NCT01954927 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. 2015 Clinical trials update in sickle cell anemia.
   Archer N, Galacteros F, Brugnara C. · · 2015 · cited 25× · PMID 26178236 · DOI 10.1002/ajh.24116
2. New insights into the pathophysiology and development of novel therapies for sickle cell disease.
   Moerdler S, Manwani D. · · 2018 · cited 24× · PMID 30504350 · DOI 10.1182/asheducation-2018.1.493
3. Gabapentin alleviates chronic spontaneous pain and acute hypoxia-related pain in a mouse model of sickle cell disease.
   Sadler KE, Langer SN, Menzel AD, Moehring F, et al · · 2019 · cited 16× · PMID 31247672 · DOI 10.1111/bjh.16067
4. Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study.
   Nottage KA, Hankins JS, Faughnan LG, James DM, et al · · 2016 · cited 12× · PMID 27000103 · DOI 10.1177/1740774516636573
5. Gabapentin for acute pain in sickle cell disease: A randomized double-blinded placebo-controlled phase II clinical trial.
   Puri L, Nottage K, Hankins JS, Wang WC, et al · · 2021 · cited 5× · PMID 35844692 · DOI 10.1002/jha2.188