None listed
Conditions
Brief summary
Community acquired pneumonia (CAP) is responsible for more than 14,000 hospital admissions in New Zealand each year, more than a thousand deaths, and thousands of days lost from work, education and leisure activities. Vitamin C is required for immune response, protects tissues from oxidative stress and is an essential enzyme cofactor for the synthesis of the hormones noradrenaline and vasopressin, which are central to the stress response. We have found that on admission 60% of patients have hypovitaminosis C and 96% have levels below normal (<50micromol). Two recent randomised controlled trials in intensive care units have shown that adjunctive vitamin C therapy administered to patients with sepsis and septic shock, (including CAP), reduced mortality and two old, and limited, studies in CAP and CAP/acute bronchitis had reduced length of hospital stay (LOS). Because vitamin C is consumed in higher quantities during acute inflammatory and stress responses we hypothesize that the resultant deficiency in patients with severe CAP results in an increased risk of death or delayed recovery. Aim: To determine the feasibility of performing a clinical trial of early vitamin C administration (intravenous while on IV antimicrobial therapy changing to oral when on oral antibiotics), in combination with standard antimicrobial therapy and supportive care, on the outcome of moderate/severe CAP (CURB-65 >1) in a randomised, double blind, placebo-controlled trial (RDBPCT). The issues assessed in this feasibility study will be: (1) Estimation of the effect size of vitamin C intervention on mortality in CAP to facilitate power calculations and (2) Determination of the rate of recruitment and accrual of patients hospitalised with severe CAP (CURB-65 >1).
Interventions
Vitamin C: Intravenous infusion of 2.5 g /8 hours will be started as soon as possible, but not later than 72 hours after hospital admission and within 24 hours of the documentation of a community acquired pneumonia CURB-65 severity score >1.
Intravenous vitamin C will be provided while the patient is receiving intravenous antimicrobial therapy and will continue until the patient is changed to oral antimicrobial therapy or for a maximum of 7 days.
Following the cessation of intravenous vitamin
Vitamin C: Intravenous infusion of 2.5 g /8 hours will be started as soon as possible, but not later than 72 hours after hospital admission and within 24 hours of the documentation of a community acquired pneumonia CURB-65 severity score >1. Intravenous vitamin C will be provided while the patient is receiving intravenous antimicrobial therapy and will continue until the patient is changed to oral antimicrobial therapy or for a maximum of 7 days. Following the cessation of intravenous vitamin C therapy the patient will receive a further 7 days of oral vitamin C at a dose of 1 g (2 x 500 mg chewable tablets) three times per day. This may be administered via nasogastric tube if the patient cannot swallow. The intravenous infusion of vitamin C will be made up by the attending nurse just prior to administering the agent. Five milliliters of a 500 mg/mL vitamin C IV solution (2.5 g total dose) will be drawn up and added to a 100 mL bag of normal saline and will be administered over a 20-30 minute period. A new solution will be made up and administered every 8 hours while the patient is on intravenous antimicrobial therapy or for a maximum of 7 days. Participants will receive vitamin C for a minimum of 8 days and a maximum of 14 days.
Sponsors
University of Otago
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Community acquired pneumonia (CAP) defined as: a new inflammatory infiltrate on chest radiograph and the presence of at least one of the following acute respiratory signs and symptoms: cough, sputum production, dyspnoea, core body temperature of 38.0°C or higher, auscultatory findings of abnormal breathing sounds or rales, leucocyte count > 104 cells/µL or < 4x104 cells/µL. 2) Aged > 17 years; 3) Able to provide informed consent 4) Requiring IV antibiotic therapy; 5) Moderate or severe pneumonia with a CURB-65 score > 1 at any time during their admission.
Exclusion criteria
1) Pneumonia is not the principal reason for admission; 2) CURB-65 score 0-1; 3) Pneumonia associated with bronchial obstruction, bronchiectasis, cystic fibrosis, or active tuberculosis; 4) Cannot provide informed consent 5) Previous hospitalisation within 2 weeks so that hospital-acquired pneumonia cannot be ruled out; 6) Severe immunosuppression ( eg neutropenia 350 cells/µL, or HIV positive and a CD4 cell count below 350 cells/µL, receiving cancer chemotherapy, receiving prednisone > 20 mg daily or anti-rejection medication); 7) Chronic kidney disease with a creatinine clearance <10 mls/sec), or receiving dialysis; 8) Known or suspected G6PD deficiency. 9) Pregnancy and breast feeding 10) Haemachromatosis
Outcome results
None listed