High Dose Intravenous Ascorbic Acid in Severe Sepsis

Sepsis Clinical Trial

Official title:

The Efficacy of Intravenous Ascorbic Acid in Patients With Severe Sepsis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02734147
• Other study ID #: 603204
• Status: Terminated
• Phase: Phase 2
• Start date: April 1, 2016
• Est. completion date: November 23, 2017

Study information

• Verified date: January 2021
• Source: Christiana Care Health Services
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: November 23, 2017
• Est. primary completion date: October 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Drug:
• Ascorbic Acid

Other:
• Normal Saline

Locations

Country	Name	City	State
United States	Chrisitana Care Health System-Christiana Hospital	Newark	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Christiana Care Health Services

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline and 72 hours
Secondary	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.	at 72 Hours
Secondary	Ascorbic Acid Concentration at 32 Hours	Ascorbic Acid Concentration Normal Ascorbic Acid Range 0.4-2.0 mg/dL	32 Hours
Secondary	ICU Length of Stay	ICU Length of Stay in Hours	Length of ICU stay up to 200 hours
Secondary	Hospital Length of Stay	From admission until discharge from ICU in days	From ICU admission through ICU discharge, up to 2 weeks
Secondary	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.	Baseline and 72 hours
Secondary	Percentage of Participants Who Died		From initial hospital admission through discharge, up to 2 weeks.