Evidence map›Paper›PMID 25938131›Full record

ArticleThe Lancet. Haematology2014

Topical sodium nitrite for chronic leg ulcers in patients with sickle cell anaemia: a phase 1 dose-finding safety and tolerability trial.

Caterina P Minniti, Alexander M Gorbach, Dihua Xu, Yuen Yi Hon, Kara-Marie Delaney, Miles Seidel, Nitin Malik, Marlene Peters-Lawrence, Carly Cantilena, James S Nichols and 4 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Haematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02863068 (A Phase II Study of Topical Sodium Nitrite in Patients With Sickle Cell and Leg Ulcers), which is not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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.

NCT02863068 phase2terminatednot on this mapstarted 2018, after this paper: background citation

A Phase II Study of Topical Sodium Nitrite in Patients With Sickle Cell and Leg Ulcers

TypeinterventionalSponsorcaterina P minnitiRan2018 to 2023Enrolled18ConditionsSickle Cell DiseaseArmsTopical Sodium Nitrite, Placebo
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Interventions for treating leg ulcers in people with sickle cell disease.The Cochrane database of systematic reviews · 2021
    Pooled it
  2. Trial
  3. Review
  4. Review
  5. Review
  6. Review
  7. Leg ulcers in sickle cell disease patients.Jornal vascular brasileiro · 2020
    Review
  8. Review
  9. Review
  10. Review
  11. Inflammation in sickle cell disease.Clinical hemorheology and microcirculation · 2018
    Article
  12. Article
  13. Review
  14. Review
  15. 2015 Clinical trials update in sickle cell anemia.American journal of hematology · 2015
    Review
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

14 authors at 3 institutions in 1 country.

Caterina P MinnitiNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Alexander M GorbachNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Dihua XuNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Yuen Yi HonNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Kara-Marie DelaneyNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Miles SeidelNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Nitin MalikNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Marlene Peters-LawrenceNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Carly CantilenaNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
James S NicholsNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Laurel MendelsohnNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Anna ConreyNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
George GrimesNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
Gregory J KatoNational Heart, Lung and Blood Institute (Prof C P Minniti MD, D Xu PhD, K-M Delaney MD, M Peters-Lawrence RN, C Cantilena BS, J S Nichols RN, L Mendelsohn BS, A Conrey NP, Prof G J Kato MD), Pharmaceutical Development Services, Clinical Center Pharmacy Department (Y Y Hon PharmD, G Grimes PharmD), and Infrared and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering (A M Gorbach PhD, M Seidel BS, N Malik BS), National Institutes of Health, Bethesda, MD, USA; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA (Prof G J Kato).
National Institutes of Health · USNational Institutes of Health Clinical Center · USNational Institute of Biomedical Imaging and Bioengineering · US

Funding

Topical Sodium Nitrite for Chronic Leg Ulcers in Adults with Hemolytic DisordersZIAHL006127 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI MINNITI-CROUCH, CATERINA · 2011 to 2013
$2.5M
Assessment of Leg Ulcer MicrocirculationZICEB000077 · NIBIB · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · PI GORBACH, ALEXANDER · 2011 to 2015
$394k
Intramural NIH HHS ZIA HL006127Intramural NIH HHS ZIC EB000077
6 · The paper itself

Abstract

backgroundWell-tolerated and effective treatments are needed for chronic leg ulcers in sickle cell anaemia. Topical sodium nitrite, a known nitric oxide donor, enhances blood flow in ulcers and has known bacteriostatic effects. We aimed to assess the safety, tolerability, and pharmacokinetics of topical sodium nitrite in patients with sickle cell disease and chronic leg ulcers.

methodsWe enrolled adult patients from an ambulatory clinic at the National Institutes of Health (Bethesda, MD, USA) with sickle cell anaemia with leg ulcers (with a surface area of 2.5-100 cm

findingsBetween April 4, 2011, and March 19, 2013, we enrolled 18 adult patients with sickle cell anaemia and leg ulcers into our trial. We assigned three patients into each cohort, and each cohort was treated with a different concentration of sodium nitrite cream (cohort 1: 0.5%, cohort 2: 1.0%, cohort 3: 1.5%, and cohort 4: 2.0%). Patients were not enrolled into the next cohort dose until we were able to establish that no dose-limiting toxicities were observed. An additional six patients were enrolled to cohort 3a: 1.8%, after two patients in cohort 4 had asymptomatic drops in diastolic blood pressure. No grade 3-4 adverse events were observed, and there were no serious adverse events or dose-limiting side-effects. Pharmacokinetic analysis showed that systemic absorption of sodium nitrite was very low. Application of topical sodium nitrite was associated with a significant increase in peri-wound cutaneous blood flow measured by laser speckle contrast imaging (p=0.0002), corroborated by increased peri-wound skin temperature by infrared thermography (p=0.0119). We recorded a dose-dependent decrease in leg ulcer size (p=0.0012) and pain (p<0.0001). Ulcers healed completely in three patients who received the highest concentrations of topical sodium nitrite (the 1.8% and 2% cream). In our post-hoc analysis of pain, brief pain inventory scores improved in pain severity (p=0.0048) and pain interference (p=0.0013).

interpretationOur results indicate that topical sodium nitrite 2% cream is suitable for additional clinical trials in adults with sickle cell anaemia to promote healing of leg ulcers.

fundingNational Heart, Lung and Blood Institute Division of Intramural Research (National Institutes of Health).

Identifiers

PMID25938131
PMCPMC4415859
OpenAlexW2104995733

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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.