High Dose Intravenous Ascorbic Acid in Severe Sepsis

Phase 2

Terminated

• Conditions: Sepsis
• Interventions: Other: Normal Saline; Drug: Ascorbic Acid

• Registration Number: NCT02734147
• Lead Sponsor: Christiana Care Health Services

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-18
• Study Start: 2016-04-01
• Study First Submitted QC: 2016-04-11
• Study First Posted: 2016-04-12
• Primary Completion: 2017-10-08
• Study Completion: 2017-11-23
• Results First Submitted: 2020-03-06
• Status Verified: 2021-01
• Results First Submitted QC: 2021-01-28
• Last Update Submitted: 2021-01-28
• Results First Posted: 2021-02-16
• Last Update Posted: 2021-02-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Normal Saline	The placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours.
High dose IV ascorbic acid	Ascorbic Acid	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.

Primary Outcome Measures

Name	Time	Method
Change in Modified SOFA Score	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.

Secondary Outcome Measures

Name	Time	Method
Modified SOFA Score	at 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 dysfunction.
ICU Length of Stay	Length of ICU stay up to 200 hours	ICU Length of Stay in Hours
Hospital Length of Stay	From ICU admission through ICU discharge, up to 2 weeks	From admission until discharge from ICU in days
Change in PIRO Score	Baseline and 72 hours	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.
Percentage of Participants Who Died	From initial hospital admission through discharge, up to 2 weeks.
Ascorbic Acid Concentration at 32 Hours	32 Hours	Ascorbic Acid Concentration Normal Ascorbic Acid Range 0.4-2.0 mg/dL

Trial Locations

Locations (1)

Chrisitana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States