Vitamin C, Hydrocortisone and Thiamine for Septic Shock

NCT03592693 | Terminated Phase 2 DMC

• 1 other identifier: 236-16-10-2017
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

Prior data has shown that both corticosteroids and vitamin C reduce the activation of nuclear factor ƘB (NFƘB), thereby ultimately attenuating the systemic inflammatory response to sepsis/septic shock and augmenting the responsiveness to vasopressors. Therefore, the current investigators hypothesized that the combined use of vitamin C and stress-dose hydrocortisone may improve the outcomes of patients with septic shock. The investigators intend to perform a randomized, multicenter, parallel group, double-blind, placebo-controlled trial of vitamin C plus stress-dose hydrocortisone or placebo plus placebo for a total of four days after randomization of patients fulfilling the current consensus criteria for septic shock. The primary outcome will be hospital mortality, whereas the scondary outcomes will include 60-day, 28-day mortality, time to vasopressor cessation, procalcitonin clearance and change in the Sequential Organ Failure Assessment score over the first 4 days after randomization, neurologic failure-free days, and length of stay in the intensive care unit (ICU) and the hospital. Target enrollment will be 400 patients.

Conditions

Shock, Septic

Keywords

Shock, Septic; Vitamin C; Hydrocortisone

Outcome Measures

Primary Outcomes (1)

• Hospital Mortality

  Death before hospital discharge

  90 days

Secondary Outcomes (9)

• 60-day mortality

  60 days

• 28-day mortality

  28 days

• Procalcitonin (PCT) clearance .

  4 days

• Delta Sequential Organ Failure Assessment (SOFA) score

  4 days

• Neurologic failure-free days (defined as daily follow-up Glasgow Coma Score >9) within the first 28 days of follow-up

  28 days

Study Arms (2)

Vitamin-Steroid

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: Combined Vitamin C and Stress-Dose Hydrocortisone

Control

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: Placebo plus placebo

Interventions

Combined Vitamin C and Stress-Dose Hydrocortisone 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

Vitamin-Steroid

Placebo plus placebo DRUG

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

Also known as: Pacebo

Control

Eligibility Criteria

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

You may qualify if:

• i. Diagnosis of septic shock within 12 hours of admission to the ICU

You may not qualify if:

• i. Age \< 18 years ii. Pregnant iii. Patients with an end-stage underlying disease who are unlikely to survive to hospital discharge iv. Patients with acquired immunodeficiency syndrome and a CD4 count of \< 50 per microliter v. Patients with known glucose-6 phosphate dehydrogenase (G-6PD) deficiency. vi. Patients with septic shock transferred from another hospital vii. Patients with septic shock for more than 12 hours viii. Patients who require off-label treatment with corticosteroids for an indication other than sepsis ix. Lack of written, informed consent

Sponsors & Collaborators

• University of Athens: lead
• General Hospital of Nikaia "Saint Panteleimon": collaborator
• Naval Hospital, Athens: collaborator

Study Sites (2)

Evaggelismos General Hospital

Athens, Attica, 10676, Greece

Location

General Hospital of Nikaia Saint Panteleimon

Piraeus, Attica, 18454, Greece

Location

Related Publications (2)

• Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, Angus DC, Rubenfeld GD, Singer M; Sepsis Definitions Task Force. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):775-87. doi: 10.1001/jama.2016.0289.

  PMID: 26903336 BACKGROUND

• Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017 Jun;151(6):1229-1238. doi: 10.1016/j.chest.2016.11.036. Epub 2016 Dec 6.

  PMID: 27940189 BACKGROUND

MeSH Terms

Conditions

Shock, Septic

Interventions

PACEBO protocol

Condition Hierarchy (Ancestors)

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

Study Officials

• Anastasia Kotanidou, MD, PHD, Professor

  National and Kapodestrian University of Athens, Greece

  PRINCIPAL INVESTIGATOR

• Spyros D Mentzelopoulos, MD, PHD, Associate Professor

  National and Kapodestrian University of Athens, Greece

  PRINCIPAL INVESTIGATOR

• Stylianos Orfanos, MD, PHD, Professor

  National and Kapodestrian University of Athens, Greece

  STUDY DIRECTOR

• Spyros G Zakynthinos, MD, PHD, Professor

  National and Kapodestrian University of Athens, Greece

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, Investigators performing the follow-up, and care providers will be blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Intensive Care Medicine

Model Details: Randomized, multicenter, parallel group, placebo-controlled \[Vitamin c plus hydrocortisone or placebo plus placebo

Study Record Dates

• First Submitted: July 5, 2018
• First Posted: July 19, 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 (2)