Trial reportAnnals of the American Thoracic Society2015
Pharmacometabolomics of l-carnitine treatment response phenotypes in patients with septic shock.
Trial report in Annals of the American Thoracic Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- Mitochondrial dysfunction in sepsis: nutritional strategies for restoring bioenergetic homeostasis.Frontiers in cellular and infection microbiology · 2026Pooled it
- The supplementation of L-carnitine in critically ill patients with sepsis: a systematic review and meta-analysis of randomized controlled trials.European journal of medical research · 2024Pooled it
- Kidney function as a key driver of the pharmacokinetic response to high-dose L-carnitine in septic shock.Pharmacotherapy · 2023Trial
- Untargeted Metabolomics Differentiates l-Carnitine Treated Septic Shock 1-Year Survivors and Nonsurvivors.Journal of proteome research · 2019Trial
- Effect of Levocarnitine vs Placebo as an Adjunctive Treatment for Septic Shock: The Rapid Administration of Carnitine in Sepsis (RACE) Randomized Clinical Trial.JAMA network open · 2018Trial
- Metabolic footprint of sepsis and septic shock: A narrative review.World journal of critical care medicine · 2026Review
- Beyond Fluid Therapy: The Role of Vitamin C, Steroids, and Thiamine in Sepsis Management.Cureus · 2025Review
- Advances in metabolomics in critically ill patients with sepsis and septic shock.Clinical and experimental emergency medicine · 2025Article
- Sepsis, Management & Advances in Metabolomics.Nanotheranostics · 2024Review
- Pharmacokinetics in Pharmacometabolomics: Towards Personalized Medication.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Sustained Perturbation of Metabolism and Metabolic Subphenotypes Are Associated With Mortality and Protein Markers of the Host Response.Critical care explorations · 2023Article
- Peculiarities of clinical signs, course and treatment of musculoskeletal system lesions in post-COVID syndrome.Reumatologia · 2023Article
- The Metabolomics of Critical Illness.Handbook of experimental pharmacology · 2023Article
- Patient Stratification in Sepsis: Using Metabolomics to Detect Clinical Phenotypes, Sub-Phenotypes and Therapeutic Response.Metabolites · 2022Review
- Serum Levels of Acylcarnitines and Amino Acids Are Associated with Liberation from Organ Support in Patients with Septic Shock.Journal of clinical medicine · 2022Article
- NMR spectroscopy spotlighting immunogenicity induced by COVID-19 vaccination to mitigate future health concerns.Current research in immunology · 2022Review
- Past Experiences for Future Applications of Metabolomics in Critically Ill Patients with Sepsis and Septic Shocks.Metabolites · 2021Review
- Pharmacometabolomics identifies candidate predictor metabolites of an L-carnitine treatment mortality benefit in septic shock.Clinical and translational science · 2021Article
- Pharmacometabolomics by NMR in Oncology: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleSepsis therapeutics have a poor history of success in clinical trials, due in part to the heterogeneity of enrolled patients. Pharmacometabolomics could differentiate drug response phenotypes and permit a precision medicine approach to sepsis.
objectivesTo use existing serum samples from the phase 1 clinical trial of l-carnitine treatment for severe sepsis to metabolically phenotype l-carnitine responders and nonresponders.
methodsSerum samples collected before (T0) and after completion of the infusion (T24, T48) from patients randomized to either l-carnitine (12 g) or placebo for the treatment of vasopressor-dependent septic shock were assayed by untargeted (1)H-nuclear magnetic resonance metabolomics. The normalized, quantified metabolite data sets of l-carnitine- and placebo-treated patients at each time point were compared by analysis of variance with post-hoc testing for multiple comparisons. Pathway analysis was performed to statistically rank metabolic networks. MEASUREMENTS AND MAIN
resultsThirty-eight metabolites were identified in all samples. Concentrations of 3-hydroxybutyrate, acetoacetate, and 3-hydroxyisovalerate were different at T0 and over time in l-carnitine-treated survivors versus nonsurvivors. Pathway analysis of pretreatment metabolites revealed that synthesis and degradation of ketone bodies had the greatest impact in differentiating l-carnitine treatment response. Analysis of all patients based on pretreatment 3-hydroxybutyrate concentration yielded distinct phenotypes. Using the T0 median 3-hydroxybutyrate level (153 μM), patients were categorized as either high or low ketone. l-Carnitine-treated low-ketone patients had greater use of carnitine as evidenced by lower post-treatment l-carnitine levels. The l-carnitine responders also had faster resolution of vasopressor requirement and a trend toward a greater improvement in mortality at 1 year (P = 0.038) compared with patients with higher 3-hydroxybutyrate.
conclusionsThe results of this preliminary study, which were not readily apparent from the parent clinical trial, show a unique metabolite profile of l-carnitine responders and introduce pharmacometabolomics as a viable strategy for informing l-carnitine responsiveness. The approach taken in this study represents a concrete example for the application of precision medicine to sepsis therapeutics that warrants further study.
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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.