Effect of Antioxidant Vitamins on Coagulopathy and Nosocomial Pneumonia After Severe Trauma

NCT01897792 | Terminated Phase 2 Results DMC

• 1 other identifier: F101108001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effect of antioxidant vitamins (vitamins C and E) on the development of coagulation derangements and nosocomial pneumonia after severe trauma in patients.

Conditions

Coagulopathy; Nosocomial Pneumonia

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Coagulation Abnormalities

  Coagulation parameters are evaluated using standard functional tests (prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen and platelet count)and point of care functional analysis using thromboelastogram (TEG-ROTEM). A blood sample is collected upon arrival in the emergency department at 0 hours only and analyzed for markers of activation of coagulation, inflammation, and levels of vitamin C/E.

  From enrollment up to 3 days

• Number of Subjects With Ventilator-associated Pneumonia.

  Number of subjects diagnosed with pneumonia and requiring ventilator support.

  From enrollment to 3 days

• Number of Subjects With Organ Injury

  Any injury to internal organs (thoracic, abdominal or cranial cavity)

  From enrollment to 3 days

• Number of Total Blood Product Transfusions

  the number of blood product transfusions for all subjects in each group over the course of 3 days.

  From enrollment to 3 days

Secondary Outcomes (6)

• Number of Protocol Violations Per Arm.

  from enrollment up to 60 days post enrollment

• Number of Subjects Surviving to Day 28

  from enrollment up to 28 days post enrollment

• Number of Subjects With 60-day Survival

  from enrollment up to 60 days post enrollment

• Mean Number of Ventilator-free Days for Subjects

  from enrollment up to 60 days post enrollment

• Mean Number of Days in ICU.

  from enrollment up to 60 days post enrollment

Study Arms (2)

Vitamins C and E

EXPERIMENTAL

Vitamin C (1,000 mg i.v.) and Vitamin E (1,000 IU p.o. via the naso-gastric tube) administered every 8 hours starting within one hour after admission to the Emergency department for up to 5 days or until discharge from the ICU, whichever comes first.

Dietary Supplement: Vitamin C; Dietary Supplement: Vitamin E

0.9% saline and sugar pill

PLACEBO COMPARATOR

100 ml of 0.9% saline (for i.v. Vitamin C) and a p.o. placebo (sugar pill for the p.o. Vitamin E) administered every 8 hours starting within one hour after admission to the Emergency department for up to 5 days or until discharge from the ICU, whichever comes first.

Dietary Supplement: Saline (for Vitamin C); Drug: Placebo (for Vitamin E)

Interventions

Vitamin C DIETARY_SUPPLEMENT

Also known as: ascorbic acid

Vitamins C and E

Vitamin E DIETARY_SUPPLEMENT

Also known as: alpha-tocopherol

Vitamins C and E

Saline (for Vitamin C) DIETARY_SUPPLEMENT

0.9% saline administered to mimic Vitamin C

0.9% saline and sugar pill

Placebo (for Vitamin E) DRUG

Sugar pill administered to mimic Vitamin E

0.9% saline and sugar pill

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult trauma patients admitted to the emergency department at the University of Alabama at Birmingham (UAB) Hospital
• Blunt or penetrating injury
• UAB highest trauma activation

You may not qualify if:

• Age \< 19 years of age
• Patients with known bleeding diathesis or who are concurrently taking anticoagulant medication
• Patients with known liver disease
• Minor patients
• Pregnant patients (known or suspected pregnancy)
• Patients who are incarcerated
• Patients who lack a surrogate

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

The University of Alabama at Birmingham Hospital

Birmingham, Alabama, 35294, United States

Location

Related Publications (11)

• Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet JF. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway? Ann Surg. 2007 May;245(5):812-8. doi: 10.1097/01.sla.0000256862.79374.31.

  PMID: 17457176 BACKGROUND

• Brohi K, Cohen MJ, Ganter MT, Schultz MJ, Levi M, Mackersie RC, Pittet JF. Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. J Trauma. 2008 May;64(5):1211-7; discussion 1217. doi: 10.1097/TA.0b013e318169cd3c.

  PMID: 18469643 BACKGROUND

• Chesebro BB, Rahn P, Carles M, Esmon CT, Xu J, Brohi K, Frith D, Pittet JF, Cohen MJ. Increase in activated protein C mediates acute traumatic coagulopathy in mice. Shock. 2009 Dec;32(6):659-65. doi: 10.1097/SHK.0b013e3181a5a632.

  PMID: 19333141 BACKGROUND

• Cohen MJ, Bir N, Rahn P, Dotson R, Brohi K, Chesebro BB, Mackersie R, Carles M, Wiener-Kronish J, Pittet JF. Protein C depletion early after trauma increases the risk of ventilator-associated pneumonia. J Trauma. 2009 Dec;67(6):1176-81. doi: 10.1097/TA.0b013e3181c1c1bc.

  PMID: 20009664 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

• Collier BR, Giladi A, Dossett LA, Dyer L, Fleming SB, Cotton BA. Impact of high-dose antioxidants on outcomes in acutely injured patients. JPEN J Parenter Enteral Nutr. 2008 Jul-Aug;32(4):384-8. doi: 10.1177/0148607108319808.

  PMID: 18596309 BACKGROUND

• Secor D, Li F, Ellis CG, Sharpe MD, Gross PL, Wilson JX, Tyml K. Impaired microvascular perfusion in sepsis requires activated coagulation and P-selectin-mediated platelet adhesion in capillaries. Intensive Care Med. 2010 Nov;36(11):1928-34. doi: 10.1007/s00134-010-1969-3. Epub 2010 Aug 6.

  PMID: 20689935 BACKGROUND

• Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003 Jun;54(6):1127-30. doi: 10.1097/01.TA.0000069184.82147.06.

  PMID: 12813333 BACKGROUND

• MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma. 2003 Jul;55(1):39-44. doi: 10.1097/01.TA.0000075338.21177.EF.

  PMID: 12855879 BACKGROUND

• Esmon CT. The protein C pathway. Chest. 2003 Sep;124(3 Suppl):26S-32S. doi: 10.1378/chest.124.3_suppl.26s.

  PMID: 12970121 BACKGROUND

• Giladi AM, Dossett LA, Fleming SB, Abumrad NN, Cotton BA. High-dose antioxidant administration is associated with a reduction in post-injury complications in critically ill trauma patients. Injury. 2011 Jan;42(1):78-82. doi: 10.1016/j.injury.2010.01.104. Epub 2010 Feb 10.

  PMID: 20149369 BACKGROUND

MeSH Terms

Conditions

Hemostatic Disorders; Healthcare-Associated Pneumonia

Interventions

Ascorbic Acid; Vitamin E; alpha-Tocopherol; Sodium Chloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tocopherols; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Study terminated--inability to recruit patient that met inclusion criteria.

Results Point of Contact

• Title: Jean-Francois Pittet, MD
• Organization: UAB Department of Anesthesiology

jpittet@uabmc.edu

205-996-4755

Study Officials

• Jean-Francois Pittet, M.D.

  The University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Jeffrey Kerby, M.D., Ph.D.

  The University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 9, 2013
• First Posted: July 12, 2013
• Study Start: May 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: March 29, 2017
• Results First Posted: March 29, 2017

Record last verified: 2017-02

Locations

US (1)