SepsisPhase 1/2NCT01434121
Ascorbic Acid (Vitamin C) Infusion in Human Sepsis
A Phase 1/2 study testing Ascorbic Acid in people with Sepsis and Septic Shock, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
The major goal of this project is to determine whether intravenously infused ascorbic acid is safe for use as a viable therapeutic strategy in adult humans with sepsis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Septic Shock, Hypotension
- What is being tested?
- Ascorbic Acid
- 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
- May 2010to Sep 2012
- Phase
- Phase 1/2
- 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
- systemic inflammatory response: fever (38°C or greater) or hypothermia (36°C or lower), tachypnea (20 breaths/min) or need for mechanical ventilation for an acute process, tachycardia (rate 90/min or more), white blood cell count ≥ 12,000 cells/mm3 or ≤ 4,000 cells/mm3 or more than 10% band forms.
- Presumed or Known Site of Infection: Purulent sputum, chest radiograph with new infiltrate, spillage of bowel contents, radiographic or physical examination evidence of an infected collection, white blood cells in a normally sterile body fluid, positive blood culture, evidence of infected mechanical hardware by physical, radiographic, or ultrasonographic evidence.
- Evidence of Dysfunction of One or More End Organs: cardiovascular dysfunction: mean arterial pressure 60 mm Hg or less, the need for vasopressors to maintain this pressure in the presence of adequate intravascular volume (central venous pressure 12 mmHg); respiratory failure: (arterial PO2-to-FiO2 ratio of less than 250 or less than 200 in the presence of pneumonia; renal dysfunction: Urine output ≤ 0.5 ml/kg/hr for 2 hours in the presence of adequate intravascular volume or doubling of the serum creatinine; hematologic dysfunction: thrombocytopenia ≤ 80,000 platelets/mm3 or 50% decrease from baseline during the acute illness; Unexplained metabolic acidosis: arterial pH ≤ 7.3 and a plasma lactate level higher than 2.5. Hepatic Dysfunction: Acute Serum transaminase elevation greater than five times normal.
- Informed Consent: Ability to obtain informed consent within 48 hours.
Who cannot join
- Demographic Characteristics: Children (age < 18 years), pregnant women, prisoners, and other wards of the state are excluded from participation in this study.
- Informed Consent: Inability to obtain informed consent within 48 hours.
- Cognitive Impairment: In the absence of family or next of kin, if the investigators feel the patient is cognitively impaired, and unable to provide informed consent, the patient will not be accessed to the study.
- Non-English Speaking Patients: Patients who are non english speaking will not be accessed to this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
The major goal of this project is to determine whether intravenously infused ascorbic acid is safe for use as a viable therapeutic strategy in adult humans with sepsis.
Read the detailed description
Evolving data from experimental animals strongly suggests that ascorbic acid potently interrupts multiple biological processes which lead to organ injury following onset of sepsis. Data presented below suggests that ascorbic acid potently attenuates lung injury produced by septic insults. Sepsis and septic shock secondary to bacterial and fungal blood stream infections are a leading cause of death in critically ill patients. At present, 28 day mortality in septic patients averages 40% in the best of ICUs. In sepsis, disseminated intravascular coagulation produces widespread systemic microvascular thrombosis that leads to multiple organ injury (i.e., lung, liver, kidney, intestinal, cardiovascular). Despite aggressive intravascular volume resuscitation and vasopressor support, appropriate antibiotic administration, and expert critical care management, mortality remains high. Only a single agent has been approved to disrupt progressive sepsis-associated microvascular thrombosis (activated protein C, [Drodrecogin Alpha, brand name: Xigris, Lilly]). No other non-antibiotic pharmaceutical agent is currently approved for use in sepsis. Activated protein C (APC) continuous infusion protocol spans a 96 hour period. APC infusion produces significant anticoagulation, and therefore the major risk from its use is hemorrhage. Thus, recent surgery, especially neurosurgical procedures, is a major contraindication to APC use. Finally, cost stands as an important issue for APC use. A 96 hour APC infusion in a 70 kg patient at VCUHS costs the patient over $33,000 (source VCUHS Pharmacy Services). Use of APC in sepsis remains controversial and has failed to achieve widespread acceptance. The goal of the current study is to determine the safety of ascorbic acid infusion in septic humans.
- Conditions
- Sepsis, Septic Shock, Hypotension, Acute Lung Injury
- Being tested
- Ascorbic Acid, Placebo
- Medical subject headings
- Sepsis, Shock, Septic, Hypotension, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ascorbic AcidDrug
Also called Vitamin C
The infusion of either a high dose of ascorbic acid, low dose ascorbic acid, or placebo
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| High Dose Ascorbic Acid | Active comparator | Subject receives a high dose of infused Vitamin C Receives: Drug: Ascorbic Acid |
| Low Dose Ascorbic Acid | Active comparator | Subject receives a low dose of infused Vitamin C Receives: Drug: Ascorbic Acid |
| Placebo | Placebo comparator | Subject receives an infusion of saline Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Who Experienced Ascorbic Acid Infusion Related Arterial Hypotension, Vomiting, or Tachycardia in Septic Patients
There were no instances of arterial hypotension, vomiting, or tachycardia within the study population related to the study drug
Measured: during time of infusion- 96 hours from time of enrollment
Secondary outcomes (6)
Intensive Care Unit Length of Stay
Measured: subject will be followed until discharged from the ICU, has deceased, or study duration has reached 28 days from time of enrollment, whichever is first
Duration of Mechanical Ventilation
Measured: subject will be followed until mechanical ventilation has been discontinued, the subject has deceased, or study duration has reached 28 days from time of enrollment, whichever is first
Ventilator-free Days
Measured: subject will be followed until discharged from the hospital, has deceased, or study duration has reached 28 days from time of enrollment, whichever is first
Length of Time on Vasopressor Medication
Measured: during time of infusion - 96 hours from time of enrollment
Multiple Organ Dysfunction Score
Measured: during time of infusion - 96 hours from time of enrollment
Plasma Cytokine/Chemokine Levels
Measured: during time of infusions - 96 hours from time of enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2011 (estimated)
- Study startMay 2010
- Primary completionSep 2012
- Study completionSep 2012
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alpha Fowler, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01434121
- Sponsor's protocol ID
- HM12903
- Status last verified
- Jan 2018
- First submitted
- 9 Aug 2011
- Last updated
- 1 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Fowler AA 3rd, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, Farthing CA, Larus TL, Martin E, Brophy DF, Gupta S; Medical Respiratory Intensive Care Unit Nursing; Fisher BJ, Natarajan R. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014 Jan 31;12:32. doi: 10.1186/1479-5876-12-32.
PubMed 24484547
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ascorbic Acid (Vitamin C) Infusion in Human Sepsis
- ClinicalTrials.gov ID
- NCT01434121
- Acronym / sponsor ID
- HM12903
- Conditions
- Sepsis, Septic Shock, Hypotension, Acute Lung Injury
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 14 Sep 2011 (estimated)
- Results
- Posted 1 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The major goal of this project is to determine whether intravenously infused ascorbic acid is safe for use as a viable therapeutic strategy in adult humans with sepsis.
Detailed description
Evolving data from experimental animals strongly suggests that ascorbic acid potently interrupts multiple biological processes which lead to organ injury following onset of sepsis. Data presented below suggests that ascorbic acid potently attenuates lung injury produced by septic insults. Sepsis and septic shock secondary to bacterial and fungal blood stream infections are a leading cause of death in critically ill patients. At present, 28 day mortality in septic patients averages 40% in the best of ICUs. In sepsis, disseminated intravascular coagulation produces widespread systemic microvascular thrombosis that leads to multiple organ injury (i.e., lung, liver, kidney, intestinal, cardiovascular). Despite aggressive intravascular volume resuscitation and vasopressor support, appropriate antibiotic administration, and expert critical care management, mortality remains high. Only a single agent has been approved to disrupt progressive sepsis-associated microvascular thrombosis (activated protein C, [Drodrecogin Alpha, brand name: Xigris, Lilly]). No other non-antibiotic pharmaceutical agent is currently approved for use in sepsis. Activated protein C (APC) continuous infusion protocol spans a 96 hour period. APC infusion produces significant anticoagulation, and therefore the major risk from its use is hemorrhage. Thus, recent surgery, especially neurosurgical procedures, is a major contraindication to APC use. Finally, cost stands as an important issue for APC use. A 96 hour APC infusion in a 70 kg patient at VCUHS costs the patient over $33,000 (source VCUHS Pharmacy Services). Use of APC in sepsis remains controversial and has failed to achieve widespread acceptance. The goal of the current study is to determine the safety of ascorbic acid infusion in septic humans.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| High Dose Ascorbic Acid | Active comparator | Drug: Ascorbic AcidSubject receives a high dose of infused Vitamin C |
| Low Dose Ascorbic Acid | Active comparator | Drug: Ascorbic AcidSubject receives a low dose of infused Vitamin C |
| Placebo | Placebo comparator | Drug: PlaceboSubject receives an infusion of saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- systemic inflammatory response: fever (38°C or greater) or hypothermia (36°C or lower), tachypnea (20 breaths/min) or need for mechanical ventilation for an acute process, tachycardia (rate 90/min or more), white blood cell count ≥ 12,000 cells/mm3 or ≤ 4,000 cells/mm3 or more than 10% band forms.
- Presumed or Known Site of Infection: Purulent sputum, chest radiograph with new infiltrate, spillage of bowel contents, radiographic or physical examination evidence of an infected collection, white blood cells in a normally sterile body fluid, positive blood culture, evidence of infected mechanical hardware by physical, radiographic, or ultrasonographic evidence.
- Evidence of Dysfunction of One or More End Organs: cardiovascular dysfunction: mean arterial pressure 60 mm Hg or less, the need for vasopressors to maintain this pressure in the presence of adequate intravascular volume (central venous pressure 12 mmHg); respiratory failure: (arterial PO2-to-FiO2 ratio of less than 250 or less than 200 in the presence of pneumonia; renal dysfunction: Urine output ≤ 0.5 ml/kg/hr for 2 hours in the presence of adequate intravascular volume or doubling of the serum creatinine; hematologic dysfunction: thrombocytopenia ≤ 80,000 platelets/mm3 or 50% decrease from baseline during the acute illness; Unexplained metabolic acidosis: arterial pH ≤ 7.3 and a plasma lactate level higher than 2.5. Hepatic Dysfunction: Acute Serum transaminase elevation greater than five times normal.
- Informed Consent: Ability to obtain informed consent within 48 hours.
Key exclusion criteria (4 listed)
- Demographic Characteristics: Children (age < 18 years), pregnant women, prisoners, and other wards of the state are excluded from participation in this study.
- Informed Consent: Inability to obtain informed consent within 48 hours.
- Cognitive Impairment: In the absence of family or next of kin, if the investigators feel the patient is cognitively impaired, and unable to provide informed consent, the patient will not be accessed to the study.
- Non-English Speaking Patients: Patients who are non english speaking will not be accessed to this study.
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 AcidAlso: Vitamin CThe infusion of either a high dose of ascorbic acid, low dose ascorbic acid, or placebo | Drug | High Dose Ascorbic Acid, Low Dose Ascorbic Acid |
| Placebo | Drug | Placebo |
Primary outcome
Number of Patients Who Experienced Ascorbic Acid Infusion Related Arterial Hypotension, Vomiting, or Tachycardia in Septic Patients
Time frame: during time of infusion- 96 hours from time of enrollment
There were no instances of arterial hypotension, vomiting, or tachycardia within the study population related to the study drug
6 secondary outcomes
Intensive Care Unit Length of Stay
Time frame: subject will be followed until discharged from the ICU, has deceased, or study duration has reached 28 days from time of enrollment, whichever is first
Duration of Mechanical Ventilation
Time frame: subject will be followed until mechanical ventilation has been discontinued, the subject has deceased, or study duration has reached 28 days from time of enrollment, whichever is first
Ventilator-free Days
Time frame: subject will be followed until discharged from the hospital, has deceased, or study duration has reached 28 days from time of enrollment, whichever is first
Length of Time on Vasopressor Medication
Time frame: during time of infusion - 96 hours from time of enrollment
Multiple Organ Dysfunction Score
Time frame: during time of infusion - 96 hours from time of enrollment
Plasma Cytokine/Chemokine Levels
Time frame: during time of infusions - 96 hours from time of enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24484547Fowler AA 3rd, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, Farthing CA, Larus TL, Martin E, Brophy DF, Gupta S; Medical Respiratory Intensive Care Unit Nursing; Fisher BJ, Natarajan R. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014 Jan 31;12:32. doi: 10.1186/1479-5876-12-32.
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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.
Alpha Fowler, MD principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ascorbic Acid in people with Sepsis and Septic Shock, run by Virginia Commonwealth University 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 4 inclusion and 4 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: finished, as of the sponsor's last update on 1 Feb 2018. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 1 Jul 2014). 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?
Number of Patients Who Experienced Ascorbic Acid Infusion Related Arterial Hypotension, Vomiting, or Tachycardia in Septic Patients (time frame: during time of infusion- 96 hours from time of enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01434121, which also lists 1 linked publication.
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 1 Feb 2018.