This trial is a multicenter, randomized, double-blind, two-arm, parallel-group, placebo-controlled trial to investigate the effect of high dose intravenous (IV) Vitamin C as an adjunct to the standard of care for patients with severe pneumonia versus placebo in ICU.
Subjects will be randomized 1:1 to receive either high dose IV Vitamin C (12g/day) or placebo, every 6 hourly, until successful extubation (minimum 16 doses, maximum 40 doses). Placebo will be the equivalent volume of dextrose 5% given intravenously. Active drug or placebo will be prepared in a sterile method by designated personnel at each site. Active drug or placebo will be prepared in a 50cc syringe and infusion tubing attached, where both are coloured and UV-protected. The recruitment period is expected to be 24 months. Phone call follow-up will be conducted at day 60 (+7 days) post-randomization to review subjects' activities of daily living. All data will be entered electronically into REDCap. All randomized subjects will be included in the intention-to-treat analysis (ITT) dataset for primary and secondary efficacy endpoints analyses. Safety analysis will be conducted for all subjects who received at least one dose of study drug. There are no interim analyses planned in this trial. At least one safety review will be conducted at 50% target recruitment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
484
IV Vitamin C (12g/day)
IV dextrose 5%
Hospital Sultanah Bahiyah
Alor Star, Kedah, Malaysia
RECRUITINGHospital Raja Perempuan Zainab II
Kota Bharu, Kelantan, Malaysia
RECRUITINGHospital Raja Permaisuri Bainun
Ipoh, Perak, Malaysia
RECRUITINGVentilation-free days (VFD) at 28-days
Unit of measurement: Ventilation-free days
Time frame: First 28 days after start of randomization
Subdistribution hazard ratio of ventilation-free event with mortality as the competing event
Unit of measurement: Cumulative incidence curve, Subdistribution hazard ratio
Time frame: First 28 days after start of randomization
Sequential Organ Failure Assessment (SOFA) score
Unit of measurement: Point score
Time frame: Baseline, Day 4, Post intervention
Plasma C-reactive protein (CRP) level
Unit of measurement: mg/L
Time frame: Baseline, Day 4, Post intervention
28-day vasopressor-free days
Unit of measurement: Vasopressor-free day
Time frame: First 28 days after start of randomization
28-day intensive care unit-free days
Unit of measurement: ICU-free days
Time frame: First 28 days after start of randomization
60-day hospitalization-free days
Unit of measurement: Hospitalization-free days
Time frame: First 60 days after start of randomization
All-cause mortality rates at 28-day
Unit of measurement: Proportion, Percentage
Time frame: First 28 days after start of randomization
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Barthel index of activities of daily living
Unit of measurement: Point score
Time frame: Baseline, Day 60
Plasma ascorbate levels
Unit of measurement: μM
Time frame: Baseline, Day 2 (Between 8th and 9th dose OR Between 9th and 10th dose)