Effect of Anti-inflammatory and Anti-microbial Co-supplementations in Traumatic ICU Patients at High Risk of Sepsis (DrNoha-ICU)

The occurrence of sepsis in trauma patients is a very serious complication. Identifying trauma patients at high risk of sepsis was not revealed in the latest surviving sepsis campaign in 2016. Several biomarkers have been proposed for early prediction of sepsis in trauma patients as leukocyte anti sedimentation rate (LAR) and the proinflammatory cytokine monocyte chemo attractant protein-1 (MCP-1). Sepsis prophylaxis before occurrence of multi-organ failure still represents a major challenge. Vitamin D and probiotics have antimicrobial, anti-inflammatory and gut microbiota immune modulatory properties.Little is known about the effect of vitamin D and probiotics co-supplementation on the inflammatory response in trauma patients at high risk of sepsis.

Another promising strategy is the use of vitamin C in addition to thiamine. Trauma is associated with increased oxidative stress and vitamin C deficiency. High dose vitamin C is required to restore oxidant-antioxidant balance. Vitamin C and thiamine have shown promising results in treatment of sepsis. Vitamin C possesses anti-inflammatory, endothelial protective and anti-microbial effects. Thiamine is the precursor of thiamine pyrophosphate (TPP), a key enzyme in Krebs cycle.

Study Overview

• Status: Completed
• Conditions: Sepsis; Major Trauma
• Intervention / Treatment: Drug: oral lactobacillus probiotics plus intramuscular cholecalciferol; Drug: intravenous vitamin C plus thiamine

Detailed Description

This study will investigate effect of vitamin D and probiotics versus Vitamin C and thiamine on inflammatory response (represented by change in MCP-1 level), Sequential Organ Failure Assessment (SOFA) Score and Acute Physiology and Chronic Health Evaluation II (APACHE II) in trauma patients at high risk of sepsis. Secondary goal is to assess if the predictive ability of MCP-1 plus LAR to determine high risk of sepsis in major trauma intensive care patients and if there is correlation between LAR and MCP-1.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Mansoura, Egypt
    • Mansoura University-Emergency hospital-ICU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult trauma patients admitted to ICU within 24 hours from trauma onset with injury severity score (ISS) ≥ 16 will be recruited after obtaining informed consent

Exclusion Criteria:

• • Patients admitted to ICU after time exceeding 24 hours from trauma onset.

  • Patients whose age is less than 18 years.
  • Pregnant female.
  • Breast feeding women.
  • Arrest within 24 hours of admission.
  • Immune deficiency or administration of immune suppressant drugs.
  • Serum calcium greater than or equal to 10 mg/dl or phosphate greater than or equal 6 mg/dl.
  • History of primary parathyroid disease.
  • Metabolic bone disease.
  • Sarcoidosis.
  • End stage renal disease.
  • receiving intermittent renal replacement therapy (RRT).
  • Failure of enteral feeding or any contraindication to enteral administration.
  • Obesity , body mass index (BMI > 35 kg/m2)
  • Known contraindication to vitamin C or thiamine (oxalate nephropathy or known glucose-6-phosphate dehydrogenase deficiency)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Low risk group; no specific treatment will be given
NO_INTERVENTION: High risk control; no specific treatment will be given
ACTIVE_COMPARATOR: High risk DP; patients will receive one intramuscular (IM) injection of 400,000 IU of cholecalciferol on day- 1 Also, starting from day 1 and till day 6 (for consequential 6 days), patients will receive lactobacillus probiotics (10 billion colony forming unit) in a dose of 6 sachets per day	Drug: oral lactobacillus probiotics plus intramuscular cholecalciferol; According to leukocyte anti- sedimentation rate (LAR) result on day 1 patients will be classified into high risk for sepsis patients (LAR < 15 %) and low risk for sepsis patients (LAR ≥ 15%) High risk sepsis patients will be randomly allocated into one of the 3 groups (sealed opaque envelops) to vitamin D plus probiotics intervention group (HR-DP) group. to vitamin C plus vitamin B intervention group (HR-CB) group. to control group (HR-C) group that does not receive any supplement
ACTIVE_COMPARATOR: High risk CB; Patients will receive vitamin C plus thiamine starting from day 1 in a dose of 1 gm vitamin C and 200 mg thiamine intravenous 4 times at 12-hour intervals for 48 hours	Drug: intravenous vitamin C plus thiamine; starting from day 1 in a dose of 1 gm vitamin C and 200 mg thiamine intravenous 4 times at 12-hour intervals for 48 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Physiology and Chronic Health Evaluation II (APACHE II) score	minim 0 maximum 71 Increasing score is associated with increasing risk of ICU mortality	0n the Day 0-Day 6 from onset of trauma

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sequential Organ Failure Assessment (SOFA) score	minim 0 maximum 24 The acute increase of 2 or more in SOFA points indicates sepsis	0n the Day 0-Day 6 from onset of trauma
Monocyte chemo attractant protein 1 (MCP-1)	Optimum cut-off value of MCP-1 for prediction of sepsis in severe trauma ICU patients is 240.7 pg/ml The decrease in its level indicates less inflammatory response and better patient out comes	0n the Day 0-Day 6 from onset of trauma

Collaborators and Investigators

• Sponsor: Mansoura University

Publications and helpful links

General Publications

• Kamel NA, Soliman MM, Abo-Zeid MA, Shaaban MI. Effect of Anti-Inflammatory and Antimicrobial Cosupplementations on Sepsis Prevention in Critically Ill Trauma Patients at High Risk for Sepsis. Front Pharmacol. 2021 Nov 29;12:792741. doi: 10.3389/fphar.2021.792741. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 18, 2020
• Primary Completion (ACTUAL): November 30, 2020
• Study Completion (ACTUAL): October 4, 2021

Study Registration Dates

• First Submitted: December 30, 2019
• First Submitted That Met QC Criteria: December 30, 2019
• First Posted (ACTUAL): January 2, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 11, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin B Complex; Cholecalciferol; Thiamine
• Other Study ID Numbers: high risk of sepsis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No