Vitamin C, Vitamin B1 and Steroid in Sepsis

Sepsis, Severe Clinical Trial

Official title:

Effects of Vitamin C, Thiamine and Hydrocortisone in Septic Shock: a Randomized, Controlled Trial

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04039815
• Other study ID #: 107133-F
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: December 3, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: December 2018
• Source: Far Eastern Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized controlled trial to test the synergic modulation effect of vitamin C, thiamine and hydrocortisone in patients with severe sepsis or septic shock.

Description:

Management of sepsis bases on three components: infection control, haemodynamic stabilization and modulation of the septic response. Many clinical trials conducted agents to block the inflammatory cascade, such as corticosteroids, anti-endotoxins antibodies, tumor necrosis factor (TNF) antagonists, interleukin-1-receptor antagonists, and so on, but none has proven effective to date. A safe, effective, ready available therapy is desperately required. Thiamine is a key co-factor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase. All the three enzymes are required to complete Krebs Cycle to prevent from lactate production. Previous studies have found thiamine deficiency to be prevalent in septic shock and other critically ill conditions. One pilot study also proved patients with septic shock and baseline thiamine deficiency would have significant lower lactate level at 24 hours after administration of thiamine. HYPRESS (hydrocortisone for Prevention of Septic Shock) study failed to demonstrate an outcome benefit from a hydrocortisone infusion in patients with sepsis. Vitamin C is a potent antioxidant that directly scavenges oxygen free radicals, can restores other cellular antioxidants and plays a role in preserving endothelial function and microcirculatory flow as well. Though previous studies suggested that hydrocortisone and vitamin C alone have little impact on the clinical outcome of patients with sepsis. Vitamin C and hydrocortisone have many overlapping and synergic pathophysiologic effects in sepsis. Both drugs are required for the synthesis of catechlamines and increase vasopressor sensitivity. Both drugs can down-regulating the production of proinflammatory mediators, increase tight junctions between endothelial and epithelial cells, preserve endothelial function and microcirculatory flow. Marik et al published their study in CHEST (June 2017) resulting the benefits of combination of Vitamin B1, Vitamin C and hydrocortisone to severe sepsis and septic shock. However, small sample size and some bias due to imbalanced baseline and study method could confound the results. Herein, we would like to lead a randomized controlled trial to test the synergic modulation effect of vitamin C, thiamine and hydrocortisone in patients with severe sepsis or septic shock.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 80
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• aged equal or over 20

• admitted to MICU due to severe sepsis or septic shock

Exclusion Criteria:

• Patients who are pregnant

• known history of Vitamin C , Vitamin B or hydrocortisone (or other equivalent products) allergy

Related Conditions & MeSH terms

• Sepsis
• Sepsis, Severe

Intervention

Drug:
• Ascorbic acid-Vitamin B1-Hydrocortisone
intravenous Thiamine (200mg in 50 mL of 0.9% normal saline and was administered as a 30-min infusion every 12 hours for 4 days or until ICU discharge), plus Vitamin C (1.5g mixed in a 100-mL solution of normal saline and was administered as an infusion over 30 to 60 min every 6 hours for four days or until ICU discharge) as well as hydrocortisone 50mg every 6 hours (or other equivalent products) for 7 days
• Placebo
patients would receive 50mL 0.9% normal saline, 100 mL 0.9% normal saline with the same infusion rate and hydrocortisone dependent on the discretion of the attending physician

Locations

Country	Name	City	State
Taiwan	Far Eastern Memorial Hospital	Taipei County

Sponsors (1)

Lead Sponsor	Collaborator
Far Eastern Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint was the hospital survival.	hospital survival	30 days
Secondary	duration of vasopressor therapy	duration of vasopressor therapy	72 hours
Secondary	requirement for renal replacement therapy in patients with acute kidney injury (AKI)	requirement for renal replacement therapy in patients with acute kidney injury (AKI)	72 hours
Secondary	ICU length of stay (LOS)	ICU length of stay (days)	4 days
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	APACH II score (total 0~100) is a score to evaluate the mortality rate of ICU patients, higher values represent a worse outcome. It includes: (A) PaO2 (depending on FiO2) Temperature (rectal) Mean arterial pressure pH arterial Heart rate Respiratory rate Sodium (serum) Potassium (serum) Creatinine Hematocrit White blood cell count; (B) age points (score: 0~6); (C) chronic health problems (liver cirrhosis, dialysis, COPD, congestive heart failure, immunocompromised)	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	PaO2 (depending on FiO2): mmHg	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	Temperature ( Celsius degrees)	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	Mean arterial pressure : mmHg	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	pH arterial	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	Heart rate: bpm	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	Respiratory rate: 1/min	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	Sodium (serum): mmol/L	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	Potassium (serum): mmol/L	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	Creatinine: mg/dL	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	Hematocrit: %	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	White blood cell count: 10 3/µL	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	age: years	72 hours
Secondary	change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours	chronic health problems (liver cirrhosis, dialysis, COPD, congestive heart failure, immunocompromised): None: 0 point Non-surgical: 5 points Emergent operation: 5 points	72 hours
Secondary	Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours	PaO2: mm Hg	72 hours
Secondary	Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours	Platelets: ×10³/µL	72 hours
Secondary	Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours	Glasgow Coma Scale: points 15: 0 13-14: +1 10-12: +2 6-9: +3 <6: +4	72 hours
Secondary	Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours	Bilirubin: mg/dL	72 hours
Secondary	Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours	Mean arterial pressure: mmHg	72 hours
Secondary	Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours	Creatinine: mg/dL	72 hours