Clinical trial NCT02734147: High Dose Intravenous Ascorbic Acid in Severe Sepsis
Official title: The Efficacy of Intravenous Ascorbic Acid in Patients With Severe Sepsis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sepsis
Lead sponsor: Christiana Care Health Services
Sponsor class: OTHER
First posted: 2016-04-12
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 expensive inpatient disease.

1. Recent research has described the therapeutic benefits associated with ascorbic acid treatment for sepsis.
2. 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.
3. 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.


Eligibility criteria: Inclusion Criteria:

Patients with:

1. A suspected or confirmed infection with an order for intravenous antibiotics or antivirals
2. The presence of acute sepsis-induced organ dysfunction

Definition of organ dysfunction:

1. Arterial hypoxemia \[PaO2 /FiO2 \< 300\]
2. Hypotension \[systolic blood pressure (SBP) \< 90 mmHg or SBP decrease \> 40 mmHg\]
3. Lactic acidosis \[lactate \> 2.5 mmol/L\]
4. Acute kidney injury \[creatinine \>2.0 or urine output \< 0.5 ml/kg/hr for \>2 hours despite fluid resuscitation\]
5. Thrombocytopenia \[platelet count \< 100,000\]
6. Acute coagulopathy \[international normalized ratio (INR) \> 1.5\]
7. Hepatic failure \[bilirubin \> 2 mg/dL\].
8. Predisposition, Infection, Response, and Organ Failure (PIRO) score ≥ 10

Exclusion Criteria:

1. Age \< 18 years
2. Pregnancy or breastfeeding
3. Requirement for immediate surgery within the treatment protocol timeframe
4. Inability to obtain written informed consent from subject or surrogate
5. Patient to receive comfort measures only

Primary outcomes:
measure: Change in Modified SOFA Score
timeFrame: Baseline and 72 hours
Secondary outcomes:
measure: Modified SOFA Score
timeFrame: at 72 Hours
measure: Ascorbic Acid Concentration at 32 Hours
timeFrame: 32 Hours
measure: ICU Length of Stay
timeFrame: Length of ICU stay up to 200 hours
measure: Hospital Length of Stay
timeFrame: From ICU admission through ICU discharge, up to 2 weeks
measure: Change in PIRO Score
timeFrame: Baseline and 72 hours
measure: Percentage of Participants Who Died
timeFrame: From initial hospital admission through discharge, up to 2 weeks.
Other outcomes:
Locations:
city: Newark
country: United States
facility: Chrisitana Care Health System-Christiana Hospital
state: Delaware
Study officials:
affiliation: Christiana Care Health Services
name: Ryan Arnold, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Christiana Care Health Services
name: Jamie Rosini, PharmD
role: PRINCIPAL_INVESTIGATOR
References: