Effect of High Dose Intravenous Vitamin C in Severe Pneumonia (VICSEP)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pneumonia
• Intervention / Treatment: Drug: Active Ingredient; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 484
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Calvin Wong Ke Wen, MBBS MRCP; Phone Number: +6082276 666; Email: vicsep.my@gmail.com

Study Locations

• Malaysia
  • Kedah
    • Alor Setar, Kedah, Malaysia, 05460
      • Hospital Sultanah Bahiyah
      • Contact: Asmah Zainudin; Phone Number: +6047406233
      • Principal Investigator: Asmah Zainudin, MBBS MMED
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 15200
      • Hospital Raja Perempuan Zainab II
      • Contact: Wan Nasrudin Wan Ismail; Phone Number: +6097452000
      • Principal Investigator: Wan Nasrudin Wan Ismail, MD MMED FCICM
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Hospital Raja Permaisuri Bainun
      • Contact: Cheah Pike Kuan; Phone Number: +6052085000
      • Principal Investigator: Cheah Pike Kuan, MD MMED

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV Vitamin C (12g/day); IV Vitamin C 3g diluted with dextrose 5% into 50ml, given every 6 hourly (12g/day), infused over 30 minutes under close monitoring, until successful extubation (minimum 16 doses, maximum 40 doses).	Drug: Active Ingredient; IV Vitamin C (12g/day)
Placebo Comparator: Placebo; IV dextrose 5% 50ml, given every 6 hourly, infused over 30 minutes under close monitoring, until successful extubation (minimum 16 doses, maximum 40 doses).	Drug: Placebo; IV dextrose 5%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilation-free days (VFD) at 28-days	Unit of measurement: Ventilation-free days	First 28 days after start of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subdistribution hazard ratio of ventilation-free event with mortality as the competing event	Unit of measurement: Cumulative incidence curve, Subdistribution hazard ratio	First 28 days after start of randomization
Sequential Organ Failure Assessment (SOFA) score	Unit of measurement: Point score	Baseline, Day 4, Post intervention
Plasma C-reactive protein (CRP) level	Unit of measurement: mg/L	Baseline, Day 4, Post intervention
28-day vasopressor-free days	Unit of measurement: Vasopressor-free day	First 28 days after start of randomization
28-day intensive care unit-free days	Unit of measurement: ICU-free days	First 28 days after start of randomization
60-day hospitalization-free days	Unit of measurement: Hospitalization-free days	First 60 days after start of randomization
All-cause mortality rates at 28-day	Unit of measurement: Proportion, Percentage	First 28 days after start of randomization
Barthel index of activities of daily living	Unit of measurement: Point score	Baseline, Day 60
Plasma ascorbate levels	Unit of measurement: μM	Baseline, Day 2 (Between 8th and 9th dose OR Between 9th and 10th dose)

Collaborators and Investigators

• Sponsor: Clinical Research Centre, Malaysia
• Collaborators: Ain Medicare Sdn Bhd
• Investigators: Principal Investigator: Calvin Wong Ke Wen, MBBS MRCP, Hospital Umum Sarawak, Malaysia

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): December 6, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Vitamin C; Mechanical ventilation; Ascorbic acid; Critically ill; Severe pneumonia; Ventilation-free day
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: VICSEP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No