Clinical trial NCT05842382: Effect of High Dose Intravenous Vitamin C in Severe Pneumonia
Official title: Effect of High Dose Intravenous Vitamin C as an Adjunct in the Treatment of Patients With Severe Pneumonia in Intensive Care Unit: a Multi-center, Double-blinded, Two-arm, Placebo-controlled, Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pneumonia
Keywords: Severe pneumonia
Critically ill
Ascorbic acid
Vitamin C
Mechanical ventilation
Ventilation-free day
Lead sponsor: Clinical Research Centre, Malaysia
Sponsor class: OTHER
Collaborators: name: Ain Medicare Sdn Bhd
First posted: 2023-05-06
Enrollment: 484
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Primary outcomes:
measure: Ventilation-free days (VFD) at 28-days
timeFrame: First 28 days after start of randomization
Secondary outcomes:
measure: Subdistribution hazard ratio of ventilation-free event with mortality as the competing event
timeFrame: First 28 days after start of randomization
measure: Sequential Organ Failure Assessment (SOFA) score
timeFrame: Baseline, Day 4, Post intervention
measure: Plasma C-reactive protein (CRP) level
timeFrame: Baseline, Day 4, Post intervention
measure: 28-day vasopressor-free days
timeFrame: First 28 days after start of randomization
measure: 28-day intensive care unit-free days
timeFrame: First 28 days after start of randomization
measure: 60-day hospitalization-free days
timeFrame: First 60 days after start of randomization
measure: All-cause mortality rates at 28-day
timeFrame: First 28 days after start of randomization
measure: Barthel index of activities of daily living
timeFrame: Baseline, Day 60
measure: Plasma ascorbate levels
timeFrame: Baseline, Day 2 (Between 8th and 9th dose OR Between 9th and 10th dose)
Other outcomes:
Locations:
city: Alor Setar
country: Malaysia
facility: Hospital Sultanah Bahiyah
state: Kedah
city: Kota Bharu
country: Malaysia
facility: Hospital Raja Perempuan Zainab II
state: Kelantan
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
state: Perak
Study officials:
affiliation: Hospital Umum Sarawak, Malaysia
name: Calvin Wong Ke Wen, MBBS MRCP
role: PRINCIPAL_INVESTIGATOR
References: