Trial reportAmerican journal of hematology2025
Arginine Therapy for Pain in Sickle Cell Disease: A Phase-2 Randomized, Placebo-Controlled Trial.
Trial report in American journal of hematology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02536170 (Phase 2 Randomized Control Trial of Arginine Therapy for Pediatric Sickle Cell Disease Pain), which is not on this map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 2 Randomized Control Trial of Arginine Therapy for Pediatric Sickle Cell Disease Pain
Who cites it
3 citing papers in PubMed.
- Dyslipidemia is a metabolic hallmark of acute pain in sickle cell disease.medRxiv : the preprint server for health sciences · 2026Article
- Hospital Variations in Time-To-Crisis-Resolution Among Children and Adolescents With Sickle Cell Disease.American journal of hematology · 2026Article
- Emergency care for children with sickle cell disease: a focus on pain and fever.Expert review of hematology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
Abstract
We present a prospective randomized, placebo-controlled trial of intravenous arginine in patients 3-21 years hospitalized with sickle cell disease vaso-occlusive pain episodes (SCD-VOE) at two tertiary-care children's hospitals. Participants were randomized into 1 of 3 arms: Standard-dose (SD; 100 mg/kg/dose) every 8 h, Loading-dose (200 mg/kg followed by SD), or Placebo. The primary outcome was total parenteral opioid use (TPO). Secondary outcomes included time-to-crisis-resolution, pain scores, patient-reported outcomes (PROs), arginine bioavailability, and biomarkers of oxidative stress/mitochondrial function. Of 1548 patients screened, 108 were randomized (36 per study-arm; mean 12.6 ± 3.8 years, 52% female, and 65% hemoglobin-SS). This study did not meet its primary endpoint. TPO, time-to-crisis-resolution, pain scores, and PROs at discharge were similar across arms. Post hoc sensitivity analyses of children 5-16 years old demonstrated nearly double TPO utilization in those receiving placebo versus arginine (n = 87, p = 0.056), achieving significance in patients with plasma arginine < 60 μM. Arginine was low at presentation in 79% of patients (mean 50 ± 28 μM), and increased with arginine therapy (p < 0.001). Arginine bioavailability at VOE presentation inversely correlated with time-to-crisis-resolution (r = -0.39, p = 0.01) after placebo, an association eliminated by arginine supplementation (r = -0.04, p = 0.70). A dose-dependent increase in platelet-mitochondrial activity occurred after arginine versus no change after placebo (p < 0.001); plasma protein-carbonyl levels, a measure of oxidative stress, decreased after arginine therapy (p < 0.001) but increased in the placebo group (p = 0.02). SCD-VOE is associated with an acquired arginine deficiency that correlates with worse clinical outcomes. Arginine improved mitochondrial function and decreased oxidative stress compared to placebo, with clinically relevant opioid-sparing becoming significant in children with the lowest arginine concentration.
trial registrationRegistered with ClinicalTrials.gov (NCT02536170) in August 2015.
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