VICSEP: Effect of High Dose Intravenous Vitamin C in Severe Pneumonia

Sponsor

Clinical Research Centre, Malaysia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05842382

Collaborator

Ain Medicare Sdn Bhd (Other)

484

Enrollment

Locations

Arms

Anticipated Duration (Months)

161.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia	Drug: Active Ingredient Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

484 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Apr 1, 2025

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

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%

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%

Outcome Measures

Primary Outcome Measures

Ventilation-free days (VFD) at 28-days [First 28 days after start of randomization]
Unit of measurement: Ventilation-free days

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Sultanah Bahiyah	Alor Setar	Kedah	Malaysia	05460
2	Hospital Raja Perempuan Zainab II	Kota Bharu	Kelantan	Malaysia	15200
3	Hospital Raja Permaisuri Bainun	Ipoh	Perak	Malaysia	30450