Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial

Prior treatment

• New SCD drug use \< 3 months (e.g. Hydroxyurea, voxelotor, crizanlizumab, etc)
• Three or more ED visits for sickle cell related pain receiving parenteral opioids in previous 7 days (not including current emergency department visit)
• Hospital discharge within previous 7 days
• Previous randomization in this arginine phase 3 randomized controlled trial

Other illness

• Acute stroke or clinical concern for stroke
• Allergy to arginine

Lab values

• Hemoglobin less than 5 gm/dL or emergent need for red blood cell transfusion for hemodynamically unstable patient

Other

• Responds to 2 doses of IV opioids sufficiently for outpatient management
• Greater than 12 hours from first dose of intravenous opioids to treat current pain in acute care setting
• Ketamine use in the emergency department for treatment of VOE
• Glutamine within 30 days
• Acute mental status or neurological changes
• Hypotension requiring clinical intervention; hemodynamic instability; septic shock
• Use of inhaled nitric oxide, sildenafil or arginine within the last month
• Non-English speaking or requires a translator for clinical care
• Pregnancy
• PI/clinical team concerns for compliance/issues that may adversely impact study participation/outcome
• Adults 18 years or older who lack medical decision-making capacity to consent

• Age 3-21 years of age, inclusive
• Established diagnosis of sickle cell disease (any genotype)
• Pain requiring medical care in an acute care setting (emergency department, hospital ward, day hospital, clinic) not attributable to non-sickle cell causes, treated with parenteral opioids