Vitamin C, Steroids, and Thiamine, and Cerebral Autoregulation and Functional Outcome in Septic Shock

NCT03649633 | Terminated Phase 1 DMC

• 1 other identifier: 163-10-5-2018
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This study has been approved as a nested substudy of a multicenter trial (CORVICTES, Clinicaltrials.gov Identifier: NCT03592693). The current, randomized, placebo-controlled study will compare steroids/vitamin C versus placebo/placebo in septic shock, with respect to cerebral autoregulation, biomarkers, and functional outcome. The following hypotheses will be tested: The steroids/vitamin C/thiamine intervention may result in attenuation of the septic shock-associated impairment in cerebral autoregulation; and 2) The increased frequency of intact cerebral autoregulation in the intervention group may result in more neurologic failure free days and ventilator free days during a 60-day follow-up; improved survival to hospital discharge with good functional outcome; and better patient-reported health-related outcomes at 90-day follow-up.

Conditions

Septic Shock

Keywords

Shock, Septic; Cerebrovascular Circulation; Spectroscopy, Near-Infrared; Patient Reported Outcome Measure

Outcome Measures

Primary Outcomes (2)

• Cerebral autoregulation

  Cerebral autoregulation while increasing MAP from a minimum of 65-75 mmHg to a maximum of 90-100 mmHg by changing the vasopressor infusion rate.

  24-78 hours after randomization

• Cerebral blood flow

  Cerebral blood flow at an MAP of 65-75 mmHg and an MAP of 90-100 mmHg

  24-78 hours after randomization

Secondary Outcomes (5)

• Neurologic failure free days

  Days 1-60 after randomization

• Ventilator-free days

  Days 1-60 after randomization

• Favorable, Inhospital, Neurological Outcome

  Days 1-60 after randomization

• Patient-reported health-related quality of life: SF-36

  90 days after randomization

• Biomarkers

  24-72 hours after randomization

Study Arms (2)

Steroids/Vitamin C group

EXPERIMENTAL

"Combined Vitamin C and Stress-Dose Hydrocortisone": Patients with septic shock treated with 1500 mg Vitamin C every 6 hours for 4 days after randomization, and stress-dose hydrocortisone for 4 days (250 mg on day 1; and 200 mg on days 2, 3, and 4) after randomization.

Drug: Stress-dose Hydrocortisone plus Vitamin C

Control group

PLACEBO COMPARATOR

"Placebo plus placebo:" Patients with septic shock treated with placebo (corresponding to Vitamin C) and placebo (corresponding to hydrocortisone) for 4 days after randomization.

Drug: isotonic sodium chloride solution placebo plus isotonic sodium chloride solution placebo

Interventions

Stress-dose Hydrocortisone plus Vitamin C DRUG

Treatment of septic shock with vitamin C and stress-dose hydrocortisone aimed at the attenuation of the systemic inflammatory response and the improvement of vasopressor responsiveness.

Also known as: Vitamin-Steroid

Steroids/Vitamin C group

isotonic sodium chloride solution placebo plus isotonic sodium chloride solution placebo DRUG

Treatment of septic shock with placebo (corresponding to Vitamin C) and placebo (corresponding to hydrocortisone).

Also known as: Placebo-placebo

Control group

Eligibility Criteria

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

You may qualify if:

• Diagnosis of septic shock within 12 hours of admission to the intensive care unit (ICU).

You may not qualify if:

• Age \< 18 years
• Pregnancy
• Patients with a fatal underlying disease who are unlikely to survive to hospital discharge
• Patients with acquired immunodeficiency and a CD4 count of \< 50 / μL
• Patients with known glucose-6 phosphate dehydrogenase (G-6PD) deficiency.
• Patients with sepsis/septic shock transferred from another hospital
• Patients with features of sepsis/septic shock \> 12 hours
• Patients who require treatment with corticosteroids for an indication other than sepsis
• Patients with any history of an allergic reaction

Sponsors & Collaborators

• University of Athens: lead

Study Sites (1)

Evaggelismos General Hospital

Athens, Attica, 10676, Greece

Location

MeSH Terms

Conditions

Shock, Septic

Interventions

Ascorbic Acid; Placebo Effect

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Effect Modifier, Epidemiologic; Epidemiologic Factors; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Spyros D Mentzelopoulos, MD, PhD

  University of Athens Medical School

  PRINCIPAL INVESTIGATOR

• Anastasia Kotanidou, MD, PhD

  University of Athens Medical School

  PRINCIPAL INVESTIGATOR

• Stylianos Orfanos, MD, PhD

  University of Athens Medical School

  STUDY DIRECTOR

• Spyros G Zakynthinos, MD. PhD

  University of Athens Medical School

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, Care Provider, Investigator, Outcomes Assessor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Intensive Care Medicine

Model Details: Single-center, prospective, randomized, doubleblind, placebo-controlled, parallel-group clinical trial.

Study Record Dates

• First Submitted: August 24, 2018
• First Posted: August 28, 2018
• Study Start: September 6, 2018
• Primary Completion: January 16, 2023
• Study Completion: January 16, 2023
• Last Updated: December 19, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)