Clinical trial NCT04039815: Vitamin C, Vitamin B1 and Steroid in Sepsis
Official title: Effects of Vitamin C, Thiamine and Hydrocortisone in Septic Shock: a Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Sepsis, Severe
Lead sponsor: Far Eastern Memorial Hospital
Sponsor class: OTHER
First posted: 2019-07-31
Enrollment: 80
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blind, randomized-controlled trial
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: The primary endpoint was the hospital survival.
timeFrame: 30 days
Secondary outcomes:
measure: duration of vasopressor therapy
timeFrame: 72 hours
measure: requirement for renal replacement therapy in patients with acute kidney injury (AKI)
timeFrame: 72 hours
measure: ICU length of stay (LOS)
timeFrame: 4 days
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
timeFrame: 72 hours
measure: Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
timeFrame: 72 hours
measure: Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
timeFrame: 72 hours
measure: Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
timeFrame: 72 hours
measure: Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
timeFrame: 72 hours
measure: Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
timeFrame: 72 hours
measure: Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
timeFrame: 72 hours
Other outcomes:
Locations:
city: Taipei County
country: Taiwan
facility: Far Eastern Memorial Hospital
Study officials:
References: