SepsisPhase 2NCT02734147
High Dose Intravenous Ascorbic Acid in Severe Sepsis
A Phase 2 study testing Ascorbic Acid and Normal Saline in people with Sepsis, run by Christiana Care Health Services at 1 site in United States.
Trial summary
Despite an organized treatment approach outlined in expert-consensus guidelines for sepsis with fluid resuscitation to treat hypovolemia, antibiotics to target the infectious insult, and vasopressors for hypotension, mortality rates for sepsis remain high and the incidence continues to rise, making sepsis the most… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Ascorbic Acid and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2016to 23 Nov 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with:
- A suspected or confirmed infection with an order for intravenous antibiotics or antivirals
- The presence of acute sepsis-induced organ dysfunction
- Definition of organ dysfunction:
- Arterial hypoxemia [PaO2 /FiO2 < 300]
- Hypotension [systolic blood pressure (SBP) < 90 mmHg or SBP decrease > 40 mmHg]
Show all 12Show fewer
- Lactic acidosis [lactate > 2.5 mmol/L]
- Acute kidney injury [creatinine >2.0 or urine output < 0.5 ml/kg/hr for >2 hours despite fluid resuscitation]
- Thrombocytopenia [platelet count < 100,000]
- Acute coagulopathy [international normalized ratio (INR) > 1.5]
- Hepatic failure [bilirubin > 2 mg/dL].
- Predisposition, Infection, Response, and Organ Failure (PIRO) score ≥ 10
Who cannot join
- Age < 18 years
- Pregnancy or breastfeeding
- Requirement for immediate surgery within the treatment protocol timeframe
- Inability to obtain written informed consent from subject or surrogate
- Patient to receive comfort measures only
Trial locations and contacts
1 site in 1 country.
United States1 site
Chrisitana Care Health System-Christiana Hospital
Newark, Delaware, 19718
About this study
Official title: The Efficacy of Intravenous Ascorbic Acid in Patients With Severe Sepsis
Despite an organized treatment approach outlined in expert-consensus guidelines for sepsis with fluid resuscitation to treat hypovolemia, antibiotics to target the infectious insult, and vasopressors for hypotension, mortality rates for sepsis remain high and the incidence continues to rise, making sepsis the most expensive inpatient disease.
- Recent research has described the therapeutic benefits associated with ascorbic acid treatment for sepsis.
- Researchers objectives are to perform a randomized-controlled clinical trial investigating the ability of ascorbic acid(vitamin C) administration to decrease organ dysfunction in severe sepsis. The widespread occurrence of microvascular dysfunction in sepsis leading to tissue hypoxia, mitochondrial dysfunction, and adenosine triphosphate (ATP) depletion, gives rise to organ failure.
- Patients with organ failure and sepsis (severe sepsis) are at a higher risk of death than patients with organ failure alone. Critically ill patients may have an increased requirement for ascorbic acid in sepsis and these patients frequently have levels below normal. Ascorbic acid administration, has been shown to correlate inversely with organ failure (human literature) and directly with survival (animal studies).
4,5 Intravenous ascorbic acid therapy decreases organ failure by providing a protective effect on several microvascular functions including improving capillary blood flow, decreasing microvascular permeability, and improving arteriolar responsiveness to vasoconstrictors. Defining the utility of novel agents to augment researchers care for severe sepsis is an important task as investigators continue the institutional focus on sepsis care.
- Conditions
- Sepsis
- Being tested
- Ascorbic Acid, Normal Saline
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ascorbic AcidDrug
Normal SalineOther
| Study group | Role | What they receive |
|---|---|---|
| High dose IV ascorbic acid | Active comparator | Patients will receive 67 mg/kg IV ascorbic acid in 100 ml normal saline over 30 minutes every 8 hours (200 mg/kg/day) for 72 hours. Receives: Drug: Ascorbic Acid |
| Placebo | Placebo comparator | The placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours. Receives: Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Modified SOFA Score
Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater degree of dysfunction.
Measured: Baseline and 72 hours
Secondary outcomes (6)
Modified SOFA Score
Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater dysfunction.
Measured: at 72 Hours
Ascorbic Acid Concentration at 32 Hours
Ascorbic Acid Concentration Normal Ascorbic Acid Range 0.4-2.0 mg/dL
Measured: 32 Hours
ICU Length of Stay
ICU Length of Stay in Hours
Measured: Length of ICU stay up to 200 hours
Hospital Length of Stay
From admission until discharge from ICU in days
Measured: From ICU admission through ICU discharge, up to 2 weeks
Change in PIRO Score
PIRO consists of 4 assessments, Predisposition (scored 0-9), Infection (scored 0-4), Response (scored 0-6), and Organ Failure (scored 0-14) (PIRO). The total PIRO score is the sum of all subscores and ranges from 0-33 with higher scores indicating worse health.
Measured: Baseline and 72 hours
Percentage of Participants Who Died
Measured: From initial hospital admission through discharge, up to 2 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2016 (estimated)
- Study start1 Apr 2016
- Primary completion8 Oct 2017
- Study completion23 Nov 2017
Why it stopped: The trial prematurely terminated due to the loss of funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SepsisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christiana Care Health Services
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ryan Arnold, MD, Principal investigator, Christiana Care Health ServicesJamie Rosini, PharmD, Principal investigator, Christiana Care Health Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02734147
- Sponsor's protocol ID
- 603204
- Status last verified
- Jan 2021
- First submitted
- 18 Mar 2016
- Last updated
- 16 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of Intravenous Ascorbic Acid in Patients With Severe Sepsis
- ClinicalTrials.gov ID
- NCT02734147
- Acronym / sponsor ID
- 603204
- Conditions
- Sepsis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial prematurely terminated due to the loss of funding.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Christiana Care Health ServicesUniversity, hospital or other
- Study start
- 1 Apr 2016
- Primary completion
- 8 Oct 2017 (actual)
- Study completion
- 23 Nov 2017 (actual)
- First posted
- 12 Apr 2016 (estimated)
- Results
- Posted 16 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite an organized treatment approach outlined in expert-consensus guidelines for sepsis with fluid resuscitation to treat hypovolemia, antibiotics to target the infectious insult, and vasopressors for hypotension, mortality rates for sepsis remain high and the incidence continues to rise, making sepsis the most expensive inpatient disease.
- Recent research has described the therapeutic benefits associated with ascorbic acid treatment for sepsis.
- Researchers objectives are to perform a randomized-controlled clinical trial investigating the ability of ascorbic acid(vitamin C) administration to decrease organ dysfunction in severe sepsis. The widespread occurrence of microvascular dysfunction in sepsis leading to tissue hypoxia, mitochondrial dysfunction, and adenosine triphosphate (ATP) depletion, gives rise to organ failure.
- Patients with organ failure and sepsis (severe sepsis) are at a higher risk of death than patients with organ failure alone. Critically ill patients may have an increased requirement for ascorbic acid in sepsis and these patients frequently have levels below normal. Ascorbic acid administration, has been shown to correlate inversely with organ failure (human literature) and directly with survival (animal studies).
4,5 Intravenous ascorbic acid therapy decreases organ failure by providing a protective effect on several microvascular functions including improving capillary blood flow, decreasing microvascular permeability, and improving arteriolar responsiveness to vasoconstrictors. Defining the utility of novel agents to augment researchers care for severe sepsis is an important task as investigators continue the institutional focus on sepsis care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High dose IV ascorbic acid | Active comparator | Drug: Ascorbic AcidPatients will receive 67 mg/kg IV ascorbic acid in 100 ml normal saline over 30 minutes every 8 hours (200 mg/kg/day) for 72 hours. |
| Placebo | Placebo comparator | Other: Normal SalineThe placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- A suspected or confirmed infection with an order for intravenous antibiotics or antivirals
- The presence of acute sepsis-induced organ dysfunction
- Arterial hypoxemia [PaO2 /FiO2 < 300]
- Hypotension [systolic blood pressure (SBP) < 90 mmHg or SBP decrease > 40 mmHg]
- Lactic acidosis [lactate > 2.5 mmol/L]
Key exclusion criteria (5 listed)
- Age < 18 years
- Pregnancy or breastfeeding
- Requirement for immediate surgery within the treatment protocol timeframe
- Inability to obtain written informed consent from subject or surrogate
- Patient to receive comfort measures only
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 | Drug | High dose IV ascorbic acid |
| Normal Saline | Other | Placebo |
Primary outcome
Change in Modified SOFA Score
Time frame: Baseline and 72 hours
Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater degree of dysfunction.
6 secondary outcomes
Modified SOFA Score
Time frame: at 72 Hours
Ascorbic Acid Concentration at 32 Hours
Time frame: 32 Hours
ICU Length of Stay
Time frame: Length of ICU stay up to 200 hours
Hospital Length of Stay
Time frame: From ICU admission through ICU discharge, up to 2 weeks
Change in PIRO Score
Time frame: Baseline and 72 hours
Percentage of Participants Who Died
Time frame: From initial hospital admission through discharge, up to 2 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ryan Arnold, MD principal investigator
Christiana Care Health Services
Jamie Rosini, PharmD principal investigator
Christiana Care Health Services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ascorbic Acid and Normal Saline in people with Sepsis, run by Christiana Care Health Services at 1 site in United States.
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 12 inclusion and 5 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: stopped early, as of the sponsor's last update on 16 Feb 2021. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Modified SOFA Score (time frame: Baseline and 72 hours). 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 16 Feb 2021.