Effect of High Dose Intravenous Vitamin C in Severe Pneumonia

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.

Eligibility Criteria:
Inclusion Criteria:

* Patients who are aged 18 and above
* Patients who are diagnosed with severe pneumonia
* Patients who are mechanically ventilated

Exclusion Criteria:

* Known allergy to Vitamin C
* Pregnancy
* Known history of ongoing concomitant infection
* Participation in another clinical trial and/or receipt of investigational drugs within 4 weeks prior to enrollment
* Moribund patient with multiorgan failure to the judgement of the treating physician, who is not expected to survive 24 hours
* Patient who requires home oxygen therapy or mechanical ventilation, including tracheostomy or non-invasive ventilation, except for CPAP/BIPAP for sleep-disordered breathing
* Known history of previous or current diagnosis of renal stones
* Known diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency
* Known diagnosis of hemochromatosis
* Known diagnosis of poorly controlled chronic pulmonary disease, including:

  * Chronic obstructive pulmonary disease with oxygen therapy
  * Chronic restrictive pulmonary disease with oxygen therapy
  * Bronchial asthma on Step 5 of treatment ladder as shown in Pocket Guide for Asthma Management and Prevention
  * Lung cancer in Stage IV of disease
* Known diagnosis of heart failure on anti-failure treatment or requiring mechanical hemodynamic support (e.g. LVAD), with recent hospitalization within 3 months (90 days) from the date of current admission.
* Immunocompromised state
* Known diagnosis of malignancy and ongoing chemotherapy or radiotherapy as there is evidence that antioxidant supplement before and during treatment was associated with an increased hazard of recurrence
* Known diagnosis of malignancy who had completed chemotherapy or radiotherapy with absolute neutrophil count ≤100 cells/mm3
* Known diagnosis of Stage 4 and above chronic kidney disease (GFR \<30 ml/min/1.73m2) and end-stage renal disease on regular dialysis (including peritoneal dialysis or hemodialysis)
* Known history of renal transplantation
* Absence of family members or next of kin for informed consent