{"id":"7bda6649-18b1-5251-8b2c-bb321683acdd","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-citris-exploratory-mortality-signal","predicate":"lowered_mortality_in_exploratory_secondary_analysis","statement":"Day-28 mortality was 25/84 (29.8%) with C versus 38/82 (46.3%) with placebo (P=0.03), in an exploratory analysis without adjustment for multiple comparisons.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"3f34f5f3-a083-57b6-86ca-5cce60f839b1","mechanism_event_label":"This smaller trial reported a possible survival benefit, although its main endpoints were negative.","subject":{"id":"2047867f-9872-53b2-a553-71c911d0695b","slug":"ascorbic-acid","display_name":"L-Ascorbic acid","entity_type_key":"small_molecule"},"object":{"id":"8b4e65f7-cbc2-5065-88f5-5ef9f96d45db","slug":"sepsis-day28-mortality","display_name":"Sepsis mortality at day 28","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3f34f5f3-a083-57b6-86ca-5cce60f839b1","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-citris-exploratory-mortality-signal-event","event_type":"observed_intervention","label":"This smaller trial reported a possible survival benefit, although its main endpoints were negative.","description":"Day-28 mortality was 25/84 (29.8%) with C versus 38/82 (46.3%) with placebo (P=0.03), in an exploratory analysis without adjustment for multiple comparisons.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2047867f-9872-53b2-a553-71c911d0695b","slug":"ascorbic-acid","display_name":"L-Ascorbic acid","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8b4e65f7-cbc2-5065-88f5-5ef9f96d45db","slug":"sepsis-day28-mortality","display_name":"Sepsis mortality at day 28","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo).","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"IV vitamin C 50 mg/kg in 5% dextrose every six hours for 96 hours versus dextrose placebo.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"One of 46 secondary outcomes; 43 were nonsignificant. Different eligibility and endpoint hierarchy from LOVIT. The signal is hypothesis-generating, and no cellular mediator was proven.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin C research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This smaller trial reported a possible survival benefit, although its main endpoints were negative.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human blood or whole-person endpoints","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"1f71bda3-136a-5038-a16f-2250cdfbb054","evidence_kind":"source_excerpt","locator":"Lines 1755-1765","start_line":1755,"end_line":1765,"excerpt":"### c-citris-exploratory-mortality-signal\nDay-28 mortality was 25/84 (29.8%) with C versus 38/82 (46.3%) with placebo (P=0.03), in an exploratory analysis without adjustment for multiple comparisons.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This smaller trial reported a possible survival benefit, although its main endpoints were negative.\norganism: Homo sapiens\ntissue_or_cell_type: Human blood or whole-person endpoints\nexperimental_model: CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo).\nlimitations: One of 46 secondary outcomes; 43 were nonsignificant. Different eligibility and endpoint hierarchy from LOVIT. The signal is hypothesis-generating, and no cellular mediator was proven.\nexposure: IV vitamin C 50 mg/kg in 5% dextrose every six hours for 96 hours versus dextrose placebo.\n[c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825","model_system":"CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo).","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"fa811221-13bd-5c10-adc1-eaf097c7703c","stable_key":"import-cb568d28-484a-5c2e-9fcc-2d780358e514","title":"Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"b7fd83f956abb81855f2ea23199ba14e465cd91f4a2ac560277ec21ddafd7bfc","revision_id":"6cde9bbb-d712-5746-82a6-85b144253efa","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}