High Dose Intravenous Ascorbic Acid in Severe Sepsis

NCT02734147 | Terminated Phase 2 Results DMC

• 1 other identifier: 603204
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Conditions

Sepsis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Modified SOFA Score

  at 72 Hours

• Ascorbic Acid Concentration at 32 Hours

  32 Hours

• ICU Length of Stay

  Length of ICU stay up to 200 hours

• Hospital Length of Stay

  From ICU admission through ICU discharge, up to 2 weeks

• Change in PIRO Score

  Baseline and 72 hours

Study Arms (2)

High dose IV ascorbic acid

ACTIVE COMPARATOR

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.

Drug: Ascorbic Acid

Placebo

PLACEBO COMPARATOR

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

Other: Normal Saline

Interventions

Ascorbic Acid DRUG

High dose IV ascorbic acid

Normal Saline OTHER

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with:
• A suspected or confirmed infection with an order for intravenous antibiotics or antivirals
• The presence of acute sepsis-induced organ dysfunction
• Definition of organ dysfunction:
• Arterial hypoxemia \[PaO2 /FiO2 \< 300\]
• Hypotension \[systolic blood pressure (SBP) \< 90 mmHg or SBP decrease \> 40 mmHg\]
• Lactic acidosis \[lactate \> 2.5 mmol/L\]
• Acute kidney injury \[creatinine \>2.0 or urine output \< 0.5 ml/kg/hr for \>2 hours despite fluid resuscitation\]
• Thrombocytopenia \[platelet count \< 100,000\]
• Acute coagulopathy \[international normalized ratio (INR) \> 1.5\]
• Hepatic failure \[bilirubin \> 2 mg/dL\].
• Predisposition, Infection, Response, and Organ Failure (PIRO) score ≥ 10

You may not qualify if:

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

Sponsors & Collaborators

• Christiana Care Health Services: lead

Study Sites (1)

Chrisitana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

MeSH Terms

Conditions

Sepsis

Interventions

Ascorbic Acid; Saline Solution

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Jamie Rosini, Pharm D
• Organization: Christiana Care Health Services

jrosini@christianacare.org

302-733-6364

Study Officials

• Ryan Arnold, MD

  Christiana Care Health Services

  PRINCIPAL INVESTIGATOR

• Jamie Rosini, PharmD

  Christiana Care Health Services

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: April 12, 2016
• Study Start: April 1, 2016
• Primary Completion: October 8, 2017
• Study Completion: November 23, 2017
• Last Updated: February 16, 2021
• Results First Posted: February 16, 2021

Record last verified: 2021-01

Locations

US (1)