Table 1.

LOVIT trial timeline

TIME POINTS	Study Period
	Days	Days											Months
	Enrolment/Allocation	Post-Allocation
	1	2	3	4	5–6	7	8–9	10	11–13	14	15–27	28	6 months
ENROLMENT:
Eligibility screen	x
Informed consent	x
Allocation	x
INTERVENTION:
Vitamin C or placebo	x	x	x	x
ASSESSMENTS:
Baseline variables
Source of infection	x
Severity of illness (APACHE II score)	x
Pre-existing comorbidities (Charlson comorbidity index, Clinical Frailty Score)	x
Vitamin C levela	x
Primary outcome
Death or persistent organ dysfunctionb												x
Secondary outcomes
Persistent organ dysfunction-free days in ICU, up to day 28b	x	x	x	x	x	x	x	x	x	x	x	x
Mortality at 6 months													x
HRQoL (EQ-5D-5 L)													x
Global tissue dysoxia (serum lactate concentration)	x		x			x
Organ function including renal function (SOFA score)	x	x	x	x		x		x		x		x
Inflammation biomarkers (IL-1ß, TNF-α, CRP)	x		x			x
Infection biomarkers (PCT)	x		x			x
Endothelial injury biomarkers (TM, ANG-2)	x		x			x
Occurrence of stage 3 AKIc	x	x	x	x	x	x	x	x	x	x	x	x
Acute hemolysis	x	x	x	x	x	x	x	x	x	x	x	x
Hypoglycemiad	x	x	x	x	x	x	x	x	x
Other variables
Protocol adherencee	x	x	x	x
Co-interventionsf	x	x	x	x	x	x	x	x	x	x		x

AKI acute kidney injury, ANG-2 angiopoietin-2, APACHE II score Acute Physiology and Chronic Health Evaluation II score, CRP C-reactive protein, EQ-5D-5 L questionnaire EuroQol-5D (EQ-5D), HRQoL: health-related quality of life, ICU intensive care unit, IL-1ß interleukin-1 beta, PCT procalcitonin, SOFA score Sequential Organ Failure Assessment score, TM thrombomodulin, TNF-α tumor necrosis factor-alpha

^aMust be collected before the first dose of investigational product

^bDependency on mechanical ventilation, RRT, or vasopressors

^cAs defined by KDIGO (Kidney Disease: Improving Global Outcomes) criteria²²

^dAssessed by core lab (during the time participants receive the 16 doses of the investigational product and the 7 days following the last dose)

^eReceipt of every planned dose according to schedule until completion of 96-h treatment protocol, samples collected per protocol instructions, vitamin C baseline collected before the first dose of investigational product

^fAdministration of mechanical ventilation, RRT, vasopressors, corticosteroids, thiamine, intravenous fluids, blood products, sedatives, and antimicrobials. Daily data until ICU discharge or 28 days (whichever comes first)