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

NCT04029675 | Completed DMC

• 1 other identifier: Faculty of Pharmacy_AinShamsU
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ventilator Associated Pneumonia ( VAP); Sepsis

Keywords

Vitamin C; Sepsis; Intensive care unit; Mechanically ventilation; VAP

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• change in SOFA score

  SOFA (Sepsis -related Organ Failure assessment) score

  within 7 days of administered of vitamin C

Secondary Outcomes (5)

• 28 day Mortality rate

  average 28 days

• length of stay in intensive care unit

  through the study completion, average 6 months

• changes in Glutathione Peroxidase enzyme (GPX) activity

  within 7 days of administered of vitamin C

• duration of vasopressor support

  Average28 days

• Ventilator-free days (28-days Cumulative )

  28 days

Study Arms (2)

Study Group ( High dose vitamin C group )

EXPERIMENTAL

They will receive 1.5 gm intravenous (IV) Vitamin C in 100 ml dextrose 5% (D5W) administered as an infusion over 30 to 60 minutes every 6 hours daily for 4 days or until ICU discharge.

Dietary Supplement: Vitamin C

Control Group (Daily requirements vitamin C Group )

ACTIVE COMPARATOR

They will receive standard daily requirements of Vitamin C intravenously which is 75-90 mg in 100 ml dextrose 5% (D5W) administered as an infusion over 30 to 60 minutes daily for 4 days or until ICU discharge

Dietary Supplement: Vitamin C

Interventions

Vitamin C DIETARY_SUPPLEMENT

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

Control Group (Daily requirements vitamin C Group ); Study Group ( High dose vitamin C group )

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Ain Shams University Hospitals

Cairo, EL Abbasia, 002, Egypt

Location

Related Publications (28)

• Annane D, Aegerter P, Jars-Guincestre MC, Guidet B; CUB-Rea Network. Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med. 2003 Jul 15;168(2):165-72. doi: 10.1164/rccm.2201087.

  PMID: 12851245 BACKGROUND

• 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. doi: 10.1056/NEJMoa022139.

  PMID: 12700374 BACKGROUND

• 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.

  PMID: 9218672 BACKGROUND

• 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. doi: 10.1017/S0950268805004978.

  PMID: 16490136 BACKGROUND

• 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. doi: 10.1086/315214.

  PMID: 10608764 BACKGROUND

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

  BACKGROUND

• 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.

  PMID: 18274637 BACKGROUND

• 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. doi: 10.1016/j.cyto.2004.10.010. Epub 2004 Dec 8.

  PMID: 15652449 BACKGROUND

• 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.

  PMID: 21445641 BACKGROUND

• 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. doi: 10.1378/chest.117.4_suppl_2.177s. No abstract available.

  PMID: 10816031 BACKGROUND

• American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005 Feb 15;171(4):388-416. doi: 10.1164/rccm.200405-644ST. No abstract available.

  PMID: 15699079 BACKGROUND

• 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. doi: 10.7326/0003-4819-129-6-199809150-00002.

  PMID: 9735080 BACKGROUND

• 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. doi: 10.1053/jcrc.2001.28192.

  PMID: 11689764 BACKGROUND

• Tejerina E, Frutos-Vivar F, Restrepo MI, Anzueto A, Abroug F, Palizas F, Gonzalez M, D'Empaire G, Apezteguia 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. doi: 10.1016/j.jcrc.2005.08.005.

  PMID: 16616625 BACKGROUND

• 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.

  PMID: 21679878 BACKGROUND

• 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. doi: 10.2174/1389557514666140428112602.

  PMID: 24766384 BACKGROUND

• 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.

  PMID: 24484547 BACKGROUND

• 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. doi: 10.1001/archsurg.135.3.326.

  PMID: 10722036 BACKGROUND

• 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. doi: 10.1016/s0022-4804(02)00083-5.

  PMID: 12643856 BACKGROUND

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

  BACKGROUND

• 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. doi: 10.7326/0003-4819-140-7-200404060-00010.

  PMID: 15068981 BACKGROUND

• 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. doi: 10.1097/00000658-200212000-00014.

  PMID: 12454520 BACKGROUND

• 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.

  PMID: 27162802 BACKGROUND

• Ascorbic Acid Injection.TheTorranceCompany,2015.

  BACKGROUND

• 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. doi: 10.1378/chest.101.6.1644.

  PMID: 1303622 BACKGROUND

• 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.

  PMID: 3928249 BACKGROUND

• Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.

  PMID: 11445675 RESULT

• El Driny WA, Esmat IM, Shaheen SM, Sabri NA. Efficacy of High-Dose Vitamin C Infusion on Outcomes in Sepsis Requiring Mechanical Ventilation: A Double-Blind Randomized Controlled Trial. Anesthesiol Res Pract. 2022 Jul 15;2022:4057215. doi: 10.1155/2022/4057215. eCollection 2022.

  PMID: 35873893 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Sepsis

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Sara M. Shahen, MD

  Ain Shams University

  STUDY CHAIR

• Ibrahim E. Mamdoh, MD

  Ain Shams University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Model Details: Double blinded ,Prospective, Randomized clinical trial

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 23, 2019
• Study Start: July 15, 2019
• Primary Completion: January 15, 2020
• Study Completion: February 15, 2020
• Last Updated: July 21, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)