Early administration of Vitamin C in patients with sepsis or septic shock in emergency departments: A multicenter, double blinded, randomized controlled trial: The C-EASIE trial protocol.

BACKGROUND: Sepsis is a potentially life-threatening condition characterized by a deregulated body's response to infection causing injury to its own tissues and organs. Sepsis is the primary cause of death from infection. If not recognized and treated timely, it can evolve within minutes/hours to septic shock. Sepsis is associated with an acute deficiency of Vitamin C. Despite the proof-of-concept of the benefit of administering Vitamin C in patients with sepsis or septic shock, Vitamin C administration is not yet current practice. OBJECTIVE: To investigate the potential benefit of early administration of high doses of Vitamin C in addition to standard of care in patients with sepsis or septic shock. METHODS: This phase 3b multi-center trial is conducted in 8 hospitals throughout Belgium. In total 300 patients will be randomly assigned to one of two groups in a 1:1 allocation ratio. The intervention group will receive 1.5 g Vitamin C 4 times a day during 4 days, started within 6 hours after admission. The primary outcome is the average post-baseline patient SOFA score. CONCLUSION: This trial will determine whether the early administration of Vitamin C in patients with sepsis or septic shock can lead to a more rapid solution of shock and less deterioration from sepsis to septic shock, hereby reducing morbidity and mortality as well as the length of hospital stay in this patient population. TRIAL REGISTRATION: The C-EASIE trial has been registered on the ClinicalTrials.gov website on 10 February 2021 with registration number NCT04747795. TRIAL SPONSOR: UZ Leuven (sponsor's reference S63213).

Bone turnover in prolonged critical illness: effect of vitamin D.

In prolonged critical illness, increased bone resorption and osteoblast dysfunction have been reported facing low 25 hydroxy vitamin D [25(OH)D] concentrations. The current study investigates the extent to which lack of nutritional vitamin D and time in intensive care contribute to bone loss in the critically ill. Prolonged critically ill patients (n = 22) were compared with matched controls and then randomized to daily vitamin D supplement of either +/- 200 IU (low dose) or +/- 500 IU (high dose). At intensive care admission, serum concentrations of 25(OH)D, 1,25 dihydroxyvitamin D(3), vitamin D-binding protein, ionized calcium, IL-1, and soluble IL-6-receptor were low, and PTH was normal. Circulating type-I collagen propeptides were high, alkaline phosphatase was normal, and osteocalcin was low. Bone resorption markers [(carboxy terminal cross-linked telopeptide of type I collagen (betaCTX), pyridinoline, deoxypyridinoline (DPD)] were 6-fold increased. Serum C-reactive protein (CRP) was 40-fold, IL-6 400-fold, TNFalpha levels 5-fold, and osteoprotegerin concentrations 3-fold higher than in controls. Soluble receptor activator of nuclear factor kappaB ligand was undetectable. High-dose vitamin D only slightly increased circulating 25 hydroxy vitamin D (P < 0.05), but 1,25 dihydroxyvitamin D(3) was unaltered. High-dose vitamin D slightly increased serum osteocalcin (P < 0.05) and decreased carboxy terminal propeptide type-I collagen (P < 0.05) but did not affect other bone turnover markers. Bone-specific alkaline phosphatase, urinary pyridinoline and DPD, and serum betaCTX markedly increased with time (P < 0.01). Circulating CRP and IL-6 decreased with time, whereas TNFalpha and IL-1 remained unaltered. The fall in CRP and IL-6 was more pronounced with the high- than low-dose vitamin D (P < 0.05). Except for a mirroring of betaCTX rise by a fall in osteoprotegerin, cytokines were unrelated to the progressively aggravating bone resorption. In conclusion, prolonged critically ill patients were vitamin D deficient. The currently recommended vitamin D dose did not normalize vitamin D status. Furthermore, severe bone hyperresorption further aggravated (up to 15-fold the normal values) with time in intensive care and was associated with impaired osteoblast function.