Evidence map›Paper›PMID 23645695›Full record

Trial reportHaematologica2013

A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes.

Claudia R Morris, Frans A Kuypers, Lisa Lavrisha, Michael Ansari, Nancy Sweeters, Melinee Stewart, Ginny Gildengorin, Lynne Neumayr, Elliott P Vichinsky

2 registry-linked trialsOpen access · goldAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Haematologica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 80 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 4 pooled it
5.0field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT01796678 phase2completednot on this map

Arginine Therapy in Sickle Cell Disease-VOC Clinical Trial

TypeinterventionalSponsorUCSF Benioff Children's Hospital OaklandRan2000 to 2007Enrolled56ConditionsVaso-occlusive Pain EpisodesArmsArginine, Placebo
NCT04839354 phase3completednot on this mapstarted 2021, after this paper: background citation

Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial

TypeinterventionalSponsorClaudia R. MorrisRan2021 to 2024Enrolled271ConditionsSickle Cell DiseaseArmsL-Arginine Hydrochloride, Normal saline
3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 4 syntheses or guidelines pooled it, 171 citations in OpenAlex.

  1. Antioxidant supplementation for sickle cell disease.The Cochrane database of systematic reviews · 2024
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  15. Sickle Cell Disease.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2024
    Review
  16. Respiratory management of acute chest syndrome in children with sickle cell disease.European respiratory review : an official journal of the European Respiratory Society · 2024
    Review
  17. Article
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Claudia R MorrisDepartment of Pediatrics, Division of Emergency Medicine, Emory-Children's Center for Developmental Lung Biology, Emory University School of Medicine, Atlanta, GA, USA. clauclaudia.r.morris@emory.edu
Frans A Kuypers
Lisa Lavrisha
Michael Ansari
Nancy Sweeters
Melinee Stewart
Ginny Gildengorin
Lynne Neumayr
Elliott P Vichinsky
Emory University · US

Funding

UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
Glutamine Therapy for Hemolysis-Associated Pulmonary HypertensionR01FD003531 · FDA · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI MORRIS, CLAUDIA R · 2009 to 2011
$1.2M
ARGININE THERAPY IN SICKLE CELL DISEASEK23HL004386 · NHLBI · CHILDREN'S HOSPITAL &RES CTR AT OAKLAND · PI MORRIS, CLAUDIA R · 2000 to 2004
$647k
FDA HHS 1R01FD003531-04FDA HHS R01 FD003531NCRR NIH HHS UL1 RR024131NHLBI NIH HHS K23 HL004386NHLBI NIH HHS K23 HL 04386-05
6 · The paper itself

Abstract

Painful episodes of vaso-occlusion are the leading cause of hospitalizations and emergency department visits in sickle cell disease, and are associated with increased mortality. Low nitric oxide bioavailability contributes to vasculopathy in sickle cell disease. Since arginine is the obligate substrate for nitric oxide production, and an acute deficiency is associated with pain, we hypothesized that arginine may be a beneficial treatment for pain related to sickle cell disease. Thirty-eight children with sickle cell disease hospitalized for 56 episodes of pain were randomized into this double-blinded placebo-controlled trial. Patients received L-arginine (100 mg/kg tid) or placebo for 5 days or until discharge. A significant reduction in total parenteral opioid use by 54% (1.9 ± 2.0 mg/kg versus 4.1 ± 4.1 mg/kg, P=0.02) and lower pain scores at discharge (1.9 ± 2.4 versus 3.9 ± 2.9, P=0.01) were observed in the treatment arm compared to the placebo one. There was no significant difference in hospital length of stay (4.1 ± 01.8 versus 4.8 ± 2.5 days, P=0.34), although a trend favored the arginine arm, and total opioid use was strongly correlated with the duration of the admission (r=0.86, P<0.0001). No drug-related adverse events were observed. Arginine therapy represents a novel intervention for painful vaso-occlusive episodes. A reduction of narcotic use by >50% is remarkable. Arginine is a safe and inexpensive intervention with narcotic-sparing effects that may be a beneficial adjunct to standard therapy for sickle cell-related pain in children. A large multi-center trial is warranted in order to confirm these observations.

Indexed as

HospitalizationAdolescentAnalgesics, OpioidAnemia, Sickle CellArginineChildDouble-Blind MethodFemaleHumansInfusions, IntravenousMalePainPain MeasurementProspective StudiesTreatment OutcomeAnalgesics, OpioidArginine

Identifiers

PMID23645695
PMCPMC3762093
OpenAlexW2073869392

What OpenQuestion holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.