Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial

The trial is designed to test intravenous (IV) arginine therapy in children with sickle cell disease (SCD) and vaso-occlusive painful episodes (VOE) to further knowledge on efficacy and safety of this orphan drug.

Inclusion Criteria: 1. Age 3-21 years of age, inclusive 2. Established diagnosis of sickle cell disease (any genotype) 3. 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 Exclusion Criteria: 1. Responds to 2 doses of IV opioids sufficiently for outpatient management 2. Greater than 12 hours from first dose of intravenous opioids to treat current pain in acute care setting 3. Hemoglobin less than 5 gm/dL or emergent need for red blood cell transfusion for hemodynamically unstable patient 4. Ketamine use in the emergency department for treatment of VOE 5. Glutamine within 30 days 6. New SCD drug use \< 3 months (e.g. Hydroxyurea, voxelotor, crizanlizumab, etc) 7. Acute mental status or neurological changes 8. Acute stroke or clinical concern for stroke 9. Three or more ED visits for sickle cell related pain receiving parenteral opioids in previous 7 days (not including current emergency department visit) 10. Hospital discharge within previous 7 days 11. Hypotension requiring clinical intervention; hemodynamic instability; septic shock 12. Previous randomization in this arginine phase 3 randomized controlled trial 13. Use of inhaled nitric oxide, sildenafil or arginine within the last month 14. Non-English speaking or requires a translator for clinical care 15. Pregnancy 16. Allergy to arginine 17. PI/clinical team concerns for compliance/issues that may adversely impact study participation/outcome 18. Adults 18 years or older who lack medical decision-making capacity to consent