Trial reportIntensive care medicine2025
Sepsis subtypes and differential treatment response to vitamin C: biological sub-study of the LOVIT trial.
Trial report in Intensive care medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03680274 (Lessening Organ Dysfunction With VITamin C), which is not on this map. Cited by 16 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.
Lessening Organ Dysfunction With VITamin C (LOVIT)
Who cites it
16 citing papers in PubMed.
- Population Pharmacokinetics of Intravenous Vitamin C in Adults with Sepsis: A Sub-study of the LOVIT Trial.Clinical pharmacokinetics · 2026Trial
- Vitamin C Does Not Affect Platelet Counts in Patients With Sepsis: A Post hoc Analysis of the Lessening Organ Dysfunction With Vitamin C Randomized Trial.Critical care explorations · 2025Trial
- Evaluating plasma ferritin and suPAR as treatable traits for critically ill patients with COVID-19 treated with anakinra: an exploratory analysis of the immune modulation domain of the REMAP-CAP randomised clinical trial.Critical care (London, England) · 2026Observational
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Immune responses and immunomodulation in sepsis: a call for identifying treatable mechanisms.Intensive care medicine · 2026Article
- Comparison of predictive values of Acute Physiology and Chronic Health Evaluation scores for mortality in sepsis: a systematic review and meta-analysis.World journal of emergency medicine · 2026Review
- Update on infection: from prevention to diagnosis and management.Intensive care medicine · 2026Article
- Precision medicine in sepsis: reappraising glucocorticoid therapy through the lens of molecular endotypes.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Data-driven spatial-temporal framework for exploring the heterogeneity and temporality of sepsis.Chinese medical journal · 2026Review
- The role of cytokines in septic myocardial dysfunction: a translational systematic review and meta-analysis.Annals of intensive care · 2026Review
- Vitamin C is associated with improved outcomes in patients with sepsis-induced myocardial injury: insights from the MIMIC-IV database.BMC infectious diseases · 2025Article
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- The Role of Vitamins in Sepsis: A Narrative Review.Nutrients · 2025Review
- Subphenotypes and phenotypes to resolve sepsis heterogeneity: hype or hope?Intensive care medicine · 2025Article
- Recent advances in understanding oxidative stress in sepsis: pathogenic roles and antioxidant therapeutic prospects - a narrative review.Frontiers in pharmacology · 2025Review
- Vitamin C for sepsis: from mechanisms to individualized therapy.Frontiers in medicine · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe hypothesised that the biological heterogeneity of sepsis may highlight sepsis subtypes with differences in response to intravenous vitamin C treatment in the Lessening Organ Dysfunction with VITamin C (LOVIT) trial. Our aims were to identify sepsis subtypes and to test whether sepsis subtypes have differences in treatment effect to vitamin C and describe putative biological effects of vitamin C treatment.
methodsWe measured biomarkers of inflammation, at baseline and at 7 days post-randomisation, in 457/863 (53.0%) of participants with plasma samples in the LOVIT trial. We used agglomerative hierarchical clustering on log
resultsOur cohort included 233/429 (54.3%) allocated to vitamin C and 224/434 (51.6%) allocated to placebo. A three-subtype model best explained the variance in our data. Subtype-2 had the highest, and subtype-3 had the lowest levels of inflammatory response. In paired longitudinal samples, vitamin C did not have discernible anti-inflammatory effects, with anti-inflammatory effects related to time since randomisation and concomitant hydrocortisone treatment. The treatment effect estimates (OR (95% CI)) for subtype-1, subtype-2 and subtype-3 were 1.04 (0.63-1.73), 1.33 (0.53-3.36) and 1.95 (0.85-4.49), respectively (test of heterogeneity p = 0.002).
conclusionWe report three sepsis subtypes based on inflammatory response profile. No subtype benefitted from vitamin C treatment in the LOVIT trial, with heterogeneity of treatment effect in the magnitude of harm.
trial registrationFunded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.
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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.