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Vitamin C, Steroids, and Thiamine, and Cerebral Autoregulation and Functional Outcome in Septic Shock (CORVICTES-ΥΜ)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03649633
Recruitment Status : Recruiting
First Posted : August 28, 2018
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Spyros D. Mentzelopoulos, University of Athens

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.

Condition or disease Intervention/treatment Phase
Septic Shock Drug: Stress-dose Hydrocortisone plus Vitamin C Drug: isotonic sodium chloride solution placebo plus isotonic sodium chloride solution placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Single-center, prospective, randomized, doubleblind, placebo-controlled, parallel-group clinical trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: Effect of Combined Vitamin C, Stress-dose Steroids, and Thiamine on Cerebral Autoregulation and Functional Outcomes of Patients With Septic Shock
Actual Study Start Date : September 6, 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock Vitamin C

Arm Intervention/treatment
Experimental: Steroids/Vitamin C group
"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
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.
Other Name: Vitamin-Steroid

Placebo Comparator: Control group
"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
Treatment of septic shock with placebo (corresponding to Vitamin C) and placebo (corresponding to hydrocortisone).
Other Name: Placebo-placebo




Primary Outcome Measures :
  1. Cerebral autoregulation [ Time Frame: 24-78 hours after randomization ]
    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.

  2. Cerebral blood flow [ Time Frame: 24-78 hours after randomization ]
    Cerebral blood flow at an MAP of 65-75 mmHg and an MAP of 90-100 mmHg


Secondary Outcome Measures :
  1. Neurologic failure free days [ Time Frame: Days 1-60 after randomization ]
    Neurologic failure free days from day 1 to day 60 postrandomization; patients with a Glasgow Coma Scale Score of more than 9 will be considered as neurologic failure-free.

  2. Ventilator-free days [ Time Frame: Days 1-60 after randomization ]
    Ventilator-free days from day 1 to day 60 postrandomization; on any given follow-up day, patients will be considered as ventilator-free only in the absence of any need for ventilatory support within the preceding 24 hours.

  3. Favorable, Inhospital, Neurological Outcome [ Time Frame: Days 1-60 after randomization ]
    Survival to hospital discharge with a Cerebral Performance Category Score (CPC) of 1 or 2. The CPC score has 5 categories: 1 = good cerebral performance: the patient is conscious, alert, and able to work and lead a normal life; 2 = moderate cerebral disability: the patient is conscious and capable of independent activities of daily life; disorders such as hemiplegia, seizures, ataxia, cognitive changes, and/or noncerebral organ dysfunction causing moderate disability may be present; 3 = severe cerebral disability: patient is conscious and ambulatory but dependent on others, because of severe memory disturbance or dementia, or patient is paralyzed and can communicate only with his/her eyes, as in the locked-in syndrome; severe disability from noncerebral organ dysfunction may coexist; 4 = coma or vegetative state: patient is unconscious and unable of any verbal and/or psychological interaction with the environment; and 5 = death: certified brain death.

  4. Patient-reported health-related quality of life: SF-36 [ Time Frame: 90 days after randomization ]

    Patient-reported health-related quality of life by using the Short Form-36 Quality of Life questionnaire; available from: https://repository.niddk.nih.gov/static/studies/halt-pkd/Forms/F038%20Quality%20of%20Life.pdf; https://www.optum.com/campaign/ls/outcomes-survey-request.html.

    The Short Form 36 Quality of Life Questionnaire is a validated, 36-item, generic health status measure with scales of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health, and reported health transition. The questionnaire is scored according to a norm-based scoring method. For example, assuming that an average normal person has a score of 50 in each scale, an individual respondent scoring below 45 is considered to have a "below-average" health status.


  5. Biomarkers [ Time Frame: 24-72 hours after randomization ]
    Plasma levels of tumor necrosis factor alpha (TNFa), interleukin (IL)-1 beta (1β), IL-6, IL-8, IL-10, Neuron Specific Enolase, and protein S100B at 24, 48, and 72 hours after randomization.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03649633


Contacts
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Contact: Spyros D Mentzelopoulos, MD, PhD +306975304909 sdmentzelopoulos@yahoo.com
Contact: Spyros G Zakynthinos, MD, PhD +306977673885 szakynthinos@yahoo.com

Locations
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Greece
Evaggelismos General Hospital Recruiting
Athens, Attica, Greece, 10676
Contact: Spyros D Mentzelopoulos, MD, PhD    +306975304909    sdmentzelopoulos@yahoo.com   
Principal Investigator: Spyros D Mentzelopoulos, MD, PhD         
Principal Investigator: Anastasia Kotanidou, MD, PhD         
Sub-Investigator: Sotirios Malachias, MD, PhD         
Sponsors and Collaborators
University of Athens
Investigators
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Principal Investigator: Spyros D Mentzelopoulos, MD, PhD University of Athens Medical School
Principal Investigator: Anastasia Kotanidou, MD, PhD University of Athens Medical School
Study Director: Stylianos Orfanos, MD, PhD University of Athens Medical School
Study Chair: Spyros G Zakynthinos, MD. PhD University of Athens Medical School

Publications:

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Responsible Party: Spyros D. Mentzelopoulos, Associate Professor of Intensive Care Medicine, University of Athens
ClinicalTrials.gov Identifier: NCT03649633    
Other Study ID Numbers: 163-10-5-2018
First Posted: August 28, 2018    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No specific plan

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Spyros D. Mentzelopoulos, University of Athens:
Shock, Septic
Cerebrovascular Circulation
Spectroscopy, Near-Infrared
Patient Reported Outcome Measure
Additional relevant MeSH terms:
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Shock, Septic
Shock
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Vitamins
Ascorbic Acid
Thiamine
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anti-Inflammatory Agents
Vitamin B Complex