Phase 3
N=271
Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial
Sickle Cell Disease
Bottom Line
View on ClinicalTrials.gov: NCT04839354 ↗Enrolled (actual)
271
Serious AEs
17.3%
Results posted
Jul 2025
Primary outcome: Primary: Time-to-crisis Resolution — 81.5; 88.6 hours
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- L-Arginine Hydrochloride (Drug); Normal saline (Other)
- Age
- Pediatric, Adult · 3+ yrs
- Sex
- All
- Sponsor
- Claudia R. Morris
- Primary completion
- Jul 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time-to-crisis Resolution |
81.5; 88.6 | — |
| SECONDARY Total Parenteral Opioid Use |
2.6; 1.9 | — |
| SECONDARY Change in Pain Score |
3.5; 3.7 | — |
| SECONDARY Change in Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Score |
3.5; 3.7 | — |
| SECONDARY Change in PROMIS Pain Behavior Score |
0.8; 1.0 | — |
| SECONDARY Change in PROMIS Fatigue Score |
-0.4; 0.1 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
- Hemoglobin less than 5 gm/dL or emergent need for red blood cell transfusion for hemodynamically unstable patient
- Ketamine use in the emergency department for treatment of VOE
- Glutamine within 30 days
- New SCD drug use < 3 months (e.g. Hydroxyurea, voxelotor, crizanlizumab, etc)
- Acute mental status or neurological changes
- Acute stroke or clinical concern for stroke
- 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
- Hypotension requiring clinical intervention; hemodynamic instability; septic shock
- Previous randomization in this arginine phase 3 randomized controlled trial
- Use of inhaled nitric oxide, sildenafil or arginine within the last month
- Non-English speaking or requires a translator for clinical care
- Pregnancy
- Allergy to arginine
- 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
Data sourced from ClinicalTrials.gov (NCT04839354). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.