Table 6.

Novel opioid-sparing agents targeting SCD pain

Name	Mechanism	Trial phase, type, NTC#	Primary end points	Status	Results and comments
Vaporized cannabis	Activation of cannabinoid receptors	1, RDBPC cross over, NCT01771731	Daily pain level over 5 d	Completed	All SCD genotypes; results pending
Canakinumab	IL-1β mAb	2, RDBPC, NCT02961218	Daily pain scores	Recruiting	Age 12-20 y
Buprenorphine	Partial μ agonist and κ antagonist	2, open label, NCT03492099	Hospitalization in 72 h subsequent to full analgesia rotation to buprenorphine	Active but not yet recruiting	All SCD genotypes
Ketamine*	NMDA receptor antagonist	2, open label, NCT03296345	Treatment-associated AEs	Recruiting	All SCD genotypes; age 8-25 y
		Randomized triple blinded, NCT03431285	Pain scores	Recruiting	All SCD genotypes
		Randomized triple blinded, NCT02573714	Pain scores	Recruiting	All SCD genotypes; age 4-16 y
					Intranasal ketamine
		3, randomized open label, NCT02801292	Reduction in pain scores	Not yet recruiting	All SCD genotypes; age 3-17 y
Memantine	NMDA receptor antagonist	2, single group, NCT02615847	AEs	Completed	Results pending
		2a/2b, single arm, NCT03247218	AEs	Not yet recruiting	≥10 y
Gabapentin*	Binding to voltage-gated calcium channels in neurons	2, RDBPC, NCT01954927	Percentage of patients with ≥33% pain reduction in 3 h	Recruiting	All SCD genotypes; age 1-20 y
Topical sodium nitrite	NO	2, RDBPC, NCT02863068	Tolerability	Recruiting	All SCD genotypes
		1, single arm open label, NCT01316796	Safety, tolerability, dose finding	Completed	All SCD genotypes; well tolerated with positive efficacy signals

Unless otherwise specified, study included only adult patients with HbSS or HbSβ0.

AE, adverse event; RDBPC, randomized double-blind placebo control.

^*Study drug administered during acute pain event