Sepsis, SeverePhase 4NCT04039815
Vitamin C, Vitamin B1 and Steroid in Sepsis
A Phase 4 study testing Ascorbic acid-Vitamin B1-Hydrocortisone in people with Sepsis, Severe, run by Far Eastern Memorial Hospital at 1 site in Taiwan.
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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Sepsis, Severe
- What is being tested?
- Ascorbic acid-Vitamin B1-Hydrocortisone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteTaiwan
- Study dates
- 3 Dec 2019to 31 Dec 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- aged equal or over 20
- admitted to MICU due to severe sepsis or septic shock
Who cannot join
- Patients who are pregnant
- known history of Vitamin C , Vitamin B or hydrocortisone (or other equivalent products) allergy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Sepsis, Severe
- Being tested
- Ascorbic acid-Vitamin B1-Hydrocortisone, Placebo
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ascorbic acid-Vitamin B1-HydrocortisoneDrug
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
PlaceboDrug
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
| Study group | Role | What they receive |
|---|---|---|
| ABC group (Ascorbic acid-Vitamin B1-Hydrocortisone) group | Experimental | 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 Receives: Drug: Ascorbic acid-Vitamin B1-Hydrocortisone |
| normal saline group | Placebo comparator | 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint was the hospital survival.
hospital survival
Measured: 30 days
Secondary outcomes (23)
duration of vasopressor therapy
duration of vasopressor therapy
Measured: 72 hours
requirement for renal replacement therapy in patients with acute kidney injury (AKI)
requirement for renal replacement therapy in patients with acute kidney injury (AKI)
Measured: 72 hours
ICU length of stay (LOS)
ICU length of stay (days)
Measured: 4 days
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)
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
PaO2 (depending on FiO2): mmHg
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Temperature ( Celsius degrees)
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Mean arterial pressure : mmHg
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
pH arterial
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Heart rate: bpm
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Respiratory rate: 1/min
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Sodium (serum): mmol/L
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Potassium (serum): mmol/L
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Creatinine: mg/dL
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Hematocrit: %
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
White blood cell count: 10 3/μL
Measured: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
age: years
Measured: 72 hours
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
Measured: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
PaO₂: mm Hg
Measured: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Platelets: ×10³/µL
Measured: 72 hours
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
Measured: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Bilirubin: mg/dL
Measured: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Mean arterial pressure: mmHg
Measured: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Creatinine: mg/dL
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2019
- Study start3 Dec 2019
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sepsis, SevereStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double blind, randomized-controlled trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Far Eastern Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04039815
- Sponsor's protocol ID
- 107133-F
- Status last verified
- Dec 2018
- First submitted
- 11 Dec 2018
- Last updated
- 6 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD are not to be shared with other researchers
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Vitamin C, Thiamine and Hydrocortisone in Septic Shock: a Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT04039815
- Acronym / sponsor ID
- 107133-F
- Conditions
- Sepsis, Severe
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Far Eastern Memorial HospitalUniversity, hospital or other
- Study start
- 3 Dec 2019 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 31 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- double blind, randomized-controlled trial
| Arm | Type | Receives |
|---|---|---|
| ABC group (Ascorbic acid-Vitamin B1-Hydrocortisone) group | Experimental | Drug: Ascorbic acid-Vitamin B1-Hydrocortisonepatients 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 |
| normal saline group | Placebo comparator | Drug: Placebopatients 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 |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- aged equal or over 20
- admitted to MICU due to severe sepsis or septic shock
Key exclusion criteria (2 listed)
- Patients who are pregnant
- known history of Vitamin C , Vitamin B or hydrocortisone (or other equivalent products) allergy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ascorbic acid-Vitamin B1-Hydrocortisoneintravenous 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 | Drug | ABC group (Ascorbic acid-Vitamin B1-Hydrocortisone) group |
| Placebopatients 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 | normal saline group |
Primary outcome
The primary endpoint was the hospital survival.
Time frame: 30 days
hospital survival
23 secondary outcomes
duration of vasopressor therapy
Time frame: 72 hours
requirement for renal replacement therapy in patients with acute kidney injury (AKI)
Time frame: 72 hours
ICU length of stay (LOS)
Time frame: 4 days
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
change of Acute Physiology And Chronic Health Evaluation II (APACH II) score over the first 72 hours
Time frame: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time frame: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time frame: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time frame: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time frame: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time frame: 72 hours
Sequential Organ Failure Assessment score (SOFA score) over the first 72 hours
Time frame: 72 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2019.
- Individual participant dataSharing planned: No. IPD are not to be shared with other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ascorbic acid-Vitamin B1-Hydrocortisone in people with Sepsis, Severe, run by Far Eastern Memorial Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint was the hospital survival. (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2019.