High Dose of Vitamin C on Mechanically Ventilated Septic Patients in Intensive Care Unit

Sepsis Clinical Trial

Official title:

The Effect of High Dose of Vitamin C on the Clinical Outcome of Mechanically Ventilated Patients Following Sepsis in Intensive Care Unit

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04029675
• Other study ID #: Faculty of Pharmacy_AinShamsU
• Status: Completed
• Phase: N/A
• Start date: July 15, 2019
• Est. completion date: February 15, 2020

Study information

• Verified date: July 2020
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prospective, Randomized clinical trial study will be carried out in intensive care unit in Ain Shams University Hospitals on 40 forty septic patients admitted to ICU and mechanically ventilated.

Description:

This study will be carried out in intensive care unit in Ain Shams University Hospitals , Cairo,Egypt on 40 patients admitted to ICU that are septic patients and mechanically ventilated which will be recruited into the study . After approval from ethical committee, an informed consent will be obtained from relatives of all patients. All data of patients will be confidential with secret codes and private file for each patient. Each patient's relative will receive an explanation for the purpose of the study. The study design will be prospective , randomized clinical trial.

Methodology:

All patients will be subjected to:

1. Complete history taking.

2. Full clinical examination

3. Evaluation and monitoring of(pulse oximetry , ECG, NIBP, temperature)

4. CBC , Blood gas (for determination of (PaO2/FiO2), Blood cultures,serum Creatinine and total bilirubin were recorded daily for the first 7 days.

5. Severity scores by calculating Acute physiology and chronic health evaluation (APACHE II)score

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 15, 2020
• Est. primary completion date: January 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Male or Female

• Age from age=18 years

• Septic patient admitted to ICU and mechanically ventilated diagnosed by sepsis criteria proposed by the American College of Chest Physicians/Society of Critical Care Medicine

• Expected to survive and remain in the ICU for at least 96 hours after study entry

Exclusion Criteria:

• Age<18 years

• Pregnant females

• Patients with history of aspiration before intubation

• Respiratory distress syndrome

• Ischemic reperfusion injury

• Cancer as the cause of SIRS or sepsis

• Chronic kidney diseases

• Ongoing shock

• Allergy from interventional drug on the study

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated
• Sepsis
• Ventilator Associated Pneumonia ( VAP)

Intervention

Dietary Supplement:
• Vitamin C
Vitamin C is a strong antioxidant and has been shown to regenerate other antioxidants such as vitamin E, vitamin C also play an important role in immune function

Locations

Country	Name	City	State
Egypt	Ain Shams University Hospitals	Cairo	EL Abbasia

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (27)

- de GroothHJ,ChooWP,Spoelstra-deMan AMetal.Pharmacokinetics off our high- dose regimens of intravenousVitamin C in critically ill patients[Abstract]. IntensiveCareMed2016

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Ascorbic Acid Injection.TheTorranceCompany,2015.

Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644-55. Review. — View Citation

CavaillonJ-M.Pathophysiological role of pro-and anti-inflammatory cytokines in sepsis .Sepsis.1998;2(2):127-40.

Cook DJ, Walter SD, Cook RJ, Griffith LE, Guyatt GH, Leasa D, Jaeschke RZ, Brun-Buisson C. Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med. 1998 Sep 15;129(6):433-40. — View Citation

Fowler AA 3rd, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, Farthing CA, Larus TL, Martin E, Brophy DF, Gupta S; Medical Respiratory Intensive Care Unit Nursing, Fisher BJ, Natarajan R. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014 Jan 31;12:32. doi: 10.1186/1479-5876-12-32. — View Citation

Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis. 2000 Jan;181(1):176-80. — View Citation

Grossman RF, Fein A. Evidence-based assessment of diagnostic tests for ventilator-associated pneumonia. Executive summary. Chest. 2000 Apr;117(4 Suppl 2):177S-181S. Review. — View Citation

Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985 Oct;13(10):818-29. — View Citation

Kurt AN, Aygun AD, Godekmerdan A, Kurt A, Dogan Y, Yilmaz E. Serum IL-1beta, IL-6, IL-8, and TNF-alpha levels in early diagnosis and management of neonatal sepsis. Mediators Inflamm. 2007;2007:31397. doi: 10.1155/2007/31397. — View Citation

Leroy O, Sanders V, Girardie P, Devos P, Yazdanpanah Y, Georges H, Beaucaire G. Mortality due to ventilator-associated pneumonia: impact of medical versus surgical ICU admittance status. J Crit Care. 2001 Sep;16(3):90-7. — View Citation

Long CL, Maull KI, Krishnan RS, Laws HL, Geiger JW, Borghesi L, Franks W, Lawson TC, Sauberlich HE. Ascorbic acid dynamics in the seriously ill and injured. J Surg Res. 2003 Feb;109(2):144-8. — View Citation

Manzanares W, Biestro A, Torre MH, Galusso F, Facchin G, Hardy G. High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation. Intensive Care Med. 2011 Jul;37(7):1120-7. doi: 10.1007/s00134-011-2212-6. Epub 2011 Mar 29. — View Citation

Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003 Apr 17;348(16):1546-54. — View Citation

Nathens AB, Neff MJ, Jurkovich GJ, Klotz P, Farver K, Ruzinski JT, Radella F, Garcia I, Maier RV. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg. 2002 Dec;236(6):814-22. — View Citation

Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamua M. Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine. 2005 Feb 21;29(4):169-75. Epub 2004 Dec 8. — View Citation

Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA, Levine M. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med. 2004 Apr 6;140(7):533-7. — View Citation

Sands KE, Bates DW, Lanken PN, Graman PS, Hibberd PL, Kahn KL, Parsonnet J, Panzer R, Orav EJ, Snydman DR, Black E, Schwartz JS, Moore R, Johnson BL Jr, Platt R; Academic Medical Center Consortium Sepsis Project Working Group. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA. 1997 Jul 16;278(3):234-40. — View Citation

Sorice A, Guerriero E, Capone F, Colonna G, Castello G, Costantini S. Ascorbic acid: its role in immune system and chronic inflammation diseases. Mini Rev Med Chem. 2014 May;14(5):444-52. Review. — View Citation

Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg. 2000 Mar;135(3):326-31. — View Citation

Tanriover MD, Guven GS, Sen D, Unal S, Uzun O. Epidemiology and outcome of sepsis in a tertiary-care hospital in a developing country. Epidemiol Infect. 2006 Apr;134(2):315-22. — View Citation

Tejerina E, Frutos-Vivar F, Restrepo MI, Anzueto A, Abroug F, Palizas F, González M, D'Empaire G, Apezteguía C, Esteban A; Internacional Mechanical Ventilation Study Group. Incidence, risk factors, and outcome of ventilator-associated pneumonia. J Crit Care. 2006 Mar;21(1):56-65. — View Citation

Visser J, Labadarios D, Blaauw R. Micronutrient supplementation for critically ill adults: a systematic review and meta-analysis. Nutrition. 2011 Jul-Aug;27(7-8):745-58. doi: 10.1016/j.nut.2010.12.009. Review. — View Citation

Zabet MH, Mohammadi M, Ramezani M, Khalili H. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock. J Res Pharm Pract. 2016 Apr-Jun;5(2):94-100. doi: 10.4103/2279-042X.179569. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Incidence of Ventilator -Associated Pneumonia ( VAP)	Ventilator-associated pneumonia (VAP)is defined as pneumonia that occurs 48-72 hours or thereafter following endotracheal intubation, characterized by the presence of a new progressive infiltrate, signs of a systemic infection (fever, altered white blood cells count), changes in sputum characteristics, and detection of a causative agent	within 28 days
Primary	Plasma Vitamin C level after administration of study drug	Vitamin C is a strong antioxidant and has been shown to regenerate other antioxidants such as vitamin E, vitamin C also play an important role in immune function	within 7 days of administered of vitamin C
Primary	change in SOFA score	SOFA (Sepsis -related Organ Failure assessment) score	within 7 days of administered of vitamin C
Secondary	28 day Mortality rate		average 28 days
Secondary	length of stay in intensive care unit		through the study completion, average 6 months
Secondary	changes in Glutathione Peroxidase enzyme (GPX) activity		within 7 days of administered of vitamin C
Secondary	duration of vasopressor support		Average28 days
Secondary	Ventilator-free days (28-days Cumulative )		28 days