High Dose Intravenous Ascorbic Acid in Severe Sepsis

NCT ID: NCT02734147

Last Updated: 2021-02-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-01
• Study Completion Date: 2017-11-23

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.

Conditions

Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

High dose IV 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.

Group Type: ACTIVE_COMPARATOR

Ascorbic Acid

Intervention Type: DRUG

Placebo

The placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours.

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: OTHER

Interventions

Ascorbic Acid

Intervention Type: DRUG

Normal Saline

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Christiana Care Health Services

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ryan Arnold, MD

Role: PRINCIPAL_INVESTIGATOR

Christiana Care Health Services

Jamie Rosini, PharmD

Role: PRINCIPAL_INVESTIGATOR

Christiana Care Health Services

Locations

Chrisitana Care Health System-Christiana Hospital

Newark, Delaware, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

603204

Identifier Type: -

Identifier Source: org_study_id