Vitamin C Supplementation in Hospitalized Patients With Community-Acquired Pneumonia: Protocol for a Randomized Controlled Trial

Background:
Community-acquired pneumonia (CAP) remains a leading cause of hospitalization, morbidity, and mortality worldwide, particularly among older adults with multimorbidity and frailty. Despite advances in antimicrobial therapy, clinical outcomes have improved little, highlighting the need for safe, inexpensive adjunctive treatments. Vitamin C plays a critical role in immune function, redox homeostasis, and endothelial integrity, all disrupted during acute infection. Hypovitaminosis C is common in hospitalized patients with CAP and has been associated with increased disease severity, longer length of stay (LOS), and worse outcomes. However, prior randomized trials of vitamin C have produced inconsistent results, often focusing on critically ill patients with sepsis, using short treatment durations, and discontinuing therapy abruptly.

Objective:
The Vitamin C in Community-Acquired Pneumonia (VitCAP) trial aims to evaluate whether high-dose oral vitamin C administered over an extended period improves clinical recovery and patient-centered outcomes in adults hospitalized with CAP.

Methods:
VitCAP is a single-center, double-blind, placebo-controlled, parallel-group randomized clinical trial conducted at a tertiary hospital in Australia. Adults aged 18 years and older hospitalized with CAP will be randomized within 48 hours of admission in a 1:1 ratio to receive either oral sodium ascorbate (1 g 3 times daily for 7 days, followed by 500 mg twice daily for 30 days) or a matching placebo in addition to standard care. Randomization will be computer generated with allocation concealment via a centralized pharmacy service, and all participants, clinicians, investigators, and outcome assessors will remain blinded. The primary outcome is time to clinical stabilization, defined using standard physiological criteria. Secondary outcomes include early clinical response, symptom burden at 30 days, intensive care unit admission, need for ventilatory or vasopressor support, LOS, all-cause mortality at 30 days and 6 months, hospital readmission, health-related quality of life, and changes in inflammatory biomarkers (C-reactive protein and procalcitonin). Analyses will follow the intention-to-treat principle. The primary outcome will be analyzed using Cox proportional hazard regression adjusted for prespecified covariates, with sensitivity analyses including restricted mean survival time.

Results:
The VitCAP trial received ethics approval from the Southern Adelaide Local Health Network Human Research Ethics Committee in 2025 and funding in September 2025. Recruitment is expected to commence in 2026 and continue for 18 to 24 months. A total of 124 participants will be enrolled to provide 80% power to detect a clinically meaningful difference in time to clinical stabilization while allowing for attrition. Data analysis will follow completion of follow-up, with primary results anticipated in 2028.

Conclusions:
The VitCAP trial is designed to address important evidence gaps by evaluating sustained oral vitamin C supplementation in hospitalized patients with CAP using clinically meaningful patient-centered outcomes. If effective, vitamin C could represent a safe, low-cost, and scalable adjunct to standard CAP management.