High-Dose Vitamin C Treatment in Critically Ill COVID-19 Patients

High-Dose Vitamin C Treatment in Critically Ill COVID-19 Patients, A Retrospective Cohort Study

Acute respiratory failure due to COVİD-19 pneumonia has poor prognosis and high mortality . Both the lack of an effective antiviral treatment and the low level evidence of the recommendations presented in the guidelines on other treatment methods have highlighted supportive treatments. Studies suggest that high-dose vitamin C treatment reduces mortality in patients with sepsis and ARDS, and may also be beneficial in COVİD-19 disease. In the study; the investigator aimed to determine the effect of Vitamin C on short-term mortality and length of intensive care stay in COVID-19 patients.

Study Overview

• Status: Completed
• Conditions: Covid19; Respiratory Distress Syndrome, Adult
• Intervention / Treatment: Drug: Ascorbic acid

Detailed Description

SARS-CoV-2 causes tissue damage in the endothelium and epithelium, increased vascular permeability and increased plasma levels of IL-6, IL-2, IL-7, IL-10 causing interstitial fibrosis in the lung is considered. Considering these factors in pathogenesis, a picture with high mortality from acute respiratory failure to severe ARDS emerges in critically ill COVID-19 patients. However, despite numerous studies, an effective antiviral treatment has not yet been found in COVID-19 disease. The low level of evidence for the recommendations presented in the guidelines on both treatment and mechanical ventilation has brought supportive treatments to the agenda. Recently, many articles have been published on the potential effects of anti-inflammatory and antioxidant treatments such as high-dose vitamin C, vitamin D, zinc and ozone therapy. In particular, high-dose intravenous vitamin C treatment is inexpensive, easily accessible, and it reduces mortality in patients with sepsis and ARDS in studies, suggesting that it may be beneficial in COVID-19 disease. this is a retrospective cohort study. The main goal of the study; to compare patients who did not receive high-dose vitamin C treatment in the first period of the epidemic and those who received treatment in the next period. the investigator aimed to determine the effect of Vitamin C on short-term mortality and length of stay in intensive care in critically ill COVID-19 patients. All patients' data on age, gender, body mass index, comorbidities (diabetes mellitus, hypertension, coronary artery disease, chronic obstructive pulmonary disease, other), PaO2 / FiO2 ratios, SOFA scores, ferritin, C-Reactive Protein, procalcitonin, lactate, neutrophil and lymphocyte values will be collected by scanning the hospital information system.

• Study Type: Observational
• Enrollment (Actual): 78

Contacts and Locations

Study Locations

• Turkey
  • İstanbul
    • Sisli, İstanbul, Turkey, 34376
      • Sisli etfal training and resource hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients who admitted to the intensive care unit with the diagnosis of acute respiratory failure due to COVID-19 pneumonia

Description

Inclusion Criteria:

• Hospitalized with diagnosis of COVID-19, diagnosis confirmed by PCR test
• pneumonia due to COVID-19 was diagnosed with clinical and radiological findings
• Patients who developed acute respiratory failure (PaO2 / FiO2 300 despite the use of 6 l / min reservoir mask) caused by COVID-19 pneumonia
• Older than 18 year

Exclusion Criteria:

• Renal failure
• Hepatic failure
• End-stage malignity
• Primary lung disease (lung cancer, cardio-pulmonary edema)
• Patients who treated with tocilizumab
• Presence of diabetic ketoacidosis, use of insulin infusion, or frequent need for point-of-care glucose monitoring (>6 times/24 hour period) as determined by treating physician
• Active kidney stone
• patients with hospitalization in ICU less than 96 hours

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
C Vit; The patients who were admitted to the intensive care unit and received a high dose intravenous vitamin C protocol constituted the treatment group	Drug: Ascorbic acid; The daily administration of 6 grams of vitamin C intravenously in 4 equal doses every 6 hours occurred and the treatment lasted 96 hours. Vials containing 1.5 gr vitamin C were placed in 100 cc 5% dextrose and infused intravenously in 30-60 minutes. Prepared serum bottles and sets are wrapped with aluminum foil in order to protect them from sunlight.
non-C Vit; The patients who were admitted to the intensive care unit but did not receive the vitamin C protocol constituted the control group	Drug: Ascorbic acid; The daily administration of 6 grams of vitamin C intravenously in 4 equal doses every 6 hours occurred and the treatment lasted 96 hours. Vials containing 1.5 gr vitamin C were placed in 100 cc 5% dextrose and infused intravenously in 30-60 minutes. Prepared serum bottles and sets are wrapped with aluminum foil in order to protect them from sunlight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
short term mortality	Incidence of mortality at 28 days by all causes	days 1-28
Length of Intensive Care Unit Stay	Length of Intensive Care Unit Stay	up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
vasopressor requirement	all types of vasopressor requirement in intensive care stay	1-28 days
invasive mechanical ventilation requirement	invasive mechanical ventilation requirement	1-28 days
PaO2/FiO2 ratio	Change in PaO2/FiO2 ratio from admission to 4th day	1-4 day
C-reactive protein	Change in C-reactive protein from admission to 4th day	1-4 days
procalcitonin	Change in procalcitonin from admission to 4th day	1-4 days
Lymphocyte count	Change in Lymphocyte count from admission to 4th day	1-4 days
ferritin	Change in ferritin from admission to 4th day	1-4 days
SOFA	Change in Sequential Organ Failure Assessment score from admission to 4th day.	1-4 days

Collaborators and Investigators

• Sponsor: Sisli Hamidiye Etfal Training and Research Hospital
• Investigators: Study Chair: Surhan Çınar, Sisli etflal resource and training hospital

Publications and helpful links

General Publications

• Fowler AA 3rd, Truwit JD, Hite RD, Morris PE, DeWilde C, Priday A, Fisher B, Thacker LR 2nd, Natarajan R, Brophy DF, Sculthorpe R, Nanchal R, Syed A, Sturgill J, Martin GS, Sevransky J, Kashiouris M, Hamman S, Egan KF, Hastings A, Spencer W, Tench S, Mehkri O, Bindas J, Duggal A, Graf J, Zellner S, Yanny L, McPolin C, Hollrith T, Kramer D, Ojielo C, Damm T, Cassity E, Wieliczko A, Halquist M. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial. JAMA. 2019 Oct 1;322(13):1261-1270. doi: 10.1001/jama.2019.11825. Erratum In: JAMA. 2020 Jan 28;323(4):379.
• Fowler AA 3rd, Fisher BJ, Kashiouris MG. Vitamin C for Sepsis and Acute Respiratory Failure-Reply. JAMA. 2020 Feb 25;323(8):792-793. doi: 10.1001/jama.2019.21987. No abstract available.
• Kim WY, Jo EJ, Eom JS, Mok J, Kim MH, Kim KU, Park HK, Lee MK, Lee K. Combined vitamin C, hydrocortisone, and thiamine therapy for patients with severe pneumonia who were admitted to the intensive care unit: Propensity score-based analysis of a before-after cohort study. J Crit Care. 2018 Oct;47:211-218. doi: 10.1016/j.jcrc.2018.07.004. Epub 2018 Jul 5.
• Moskowitz A, Huang DT, Hou PC, Gong J, Doshi PB, Grossestreuer AV, Andersen LW, Ngo L, Sherwin RL, Berg KM, Chase M, Cocchi MN, McCannon JB, Hershey M, Hilewitz A, Korotun M, Becker LB, Otero RM, Uduman J, Sen A, Donnino MW; ACTS Clinical Trial Investigators. Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial. JAMA. 2020 Aug 18;324(7):642-650. doi: 10.1001/jama.2020.11946.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 16, 2021
• Primary Completion (ACTUAL): January 25, 2021
• Study Completion (ACTUAL): February 10, 2021

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (ACTUAL): January 14, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 15, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Ascorbic Acid; intensive care; coronavirus disease 2019
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: CVIT-3334

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