This two-center, open-label randomized controlled trial evaluated the effect of adjunctive thiamine, ascorbic acid, and their combination compared with 0.9% saline on the extracellular matrix-remodeling axis (matrix metalloproteinase-9 \[MMP-9\] and tissue inhibitor of metalloproteinase-1 \[TIMP-1\]) and the inflammatory-balance axis (interleukin-6 \[IL-6\] and interleukin-10 \[IL-10\]) in adult patients with sepsis. Serum biomarkers were measured by ELISA at baseline and after 72 hours and related to organ dysfunction (SOFA score), acute kidney injury, and in-hospital mortality.
Forty adults admitted to the intensive care unit with sepsis (SOFA score \>= 2 and arterial lactate \>= 2 mmol/L) were randomized using a computer-generated sequence to four parallel arms: control (0.9% saline), thiamine 200 mg, ascorbic acid 50 mg/kg body weight, or the thiamine plus ascorbic acid combination. Study drugs were infused over 60 minutes every 12 hours for three days, in addition to the standard hour-1 sepsis bundle. MMP-9, TIMP-1, IL-6, and IL-10 were quantified by ELISA at baseline and 72 hours. Outcomes included the MMP-9/TIMP-1 ratio, the IL-6/IL-10 balance, SOFA score, acute kidney injury, and in-hospital mortality.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Thiamine 200 mg IV, over 60 minutes every 12 hours for 3 days.
Ascorbic acid + Combination (thiamine + ascorbic acid)
Control (normal saline)
Haji Adam Malik General Hospital
Medan, North Sumatra, Indonesia
Universitas Sumatera Utara
Medan, North Sumatra, Indonesia
Change in serum MMP-9 concentration
Serum matrix metalloproteinase-9 (pg/mL) measured by ELISA
Time frame: Baseline and 72 hours
Change in serum TIMP-1 and MMP-9/TIMP-1 ratio
Serum TIMP-1 (pg/mL) and the MMP-9/TIMP-1 ratio by ELISA.
Time frame: Baseline and 72 hours
Change in serum IL-6 and IL-10 concentrations
Serum IL-6 and IL-10 (pg/mL) measured by ELISA
Time frame: Baseline and 72 hours
SOFA score
Sequential Organ Failure Assessment (SOFA) score, range 0-24; higher scores indicate more severe organ dysfunction
Time frame: Baseline and 72 hours
Acute kidney injury
Serum creatinine \>= 1.5 mg/dL.
Time frame: Through ICU discharge, up to 28 days
In-hospital mortality
Death from any cause during the index hospitalization
Time frame: Through hospital discharge, up to 28 days
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