Vitamin C, Vitamin B1 and Steroid in Sepsis

December 4, 2019 updated by: Far Eastern Memorial Hospital

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei County, Taiwan, 100
        • Far Eastern Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: ABC group (Ascorbic acid-Vitamin B1-Hydrocortisone) group
patients in study group, so called" ABC" (Ascorbic acid-Vitamin B1-Hydrocortisone) group, would receive 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), 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
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_COMPARATOR: normal saline group
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
Drug: 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The primary endpoint was the hospital survival.
Time Frame: 30 days
hospital survival
30 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
duration of vasopressor therapy
Time Frame: 72 hours
duration of vasopressor therapy
72 hours
requirement for renal replacement therapy in patients with acute kidney injury (AKI)
Time Frame: 72 hours
requirement for renal replacement therapy in patients with acute kidney injury (AKI)
72 hours
ICU length of stay (LOS)
Time Frame: 4 days
ICU length of stay (days)
4 days
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 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
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
PaO2 (depending on FiO2): mmHg
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
Temperature ( Celsius degrees)
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
Mean arterial pressure : mmHg
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
pH arterial
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
Heart rate: bpm
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
Respiratory rate: 1/min
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
Sodium (serum): mmol/L
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
Potassium (serum): mmol/L
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
Creatinine: mg/dL
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
Hematocrit: %
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
White blood cell count: 10 3/μL
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 72 hours
age: years
72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time Frame: 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
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time Frame: 72 hours
PaO₂: mm Hg
72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time Frame: 72 hours
Platelets: ×10³/µL
72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time Frame: 72 hours
Glasgow Coma Scale: points 15: 0 13-14: +1 10-12: +2 6-9: +3 <6: +4
72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time Frame: 72 hours
Bilirubin: mg/dL
72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time Frame: 72 hours
Mean arterial pressure: mmHg
72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time Frame: 72 hours
Creatinine: mg/dL
72 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Far Eastern Memorial Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 3, 2019

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2020

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 11, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 29, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 31, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 6, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 107133-F

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD are not to be shared with other researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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