Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Vitamin C in Post-cardiac Arrest (VITaCCA)

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: NCT03509662
Recruitment Status : Recruiting
First Posted : April 26, 2018
Last Update Posted : October 18, 2019
Sponsor:
Collaborators:
Gelderse Vallei Hospital
Sint Franciscus Gasthuis
Tergooiziekenhuizen
Amphia Hospital
Erasmus Medical Center
Noordwest Ziekenhuisgroep
Maasstad Hospital
OLVG
Information provided by (Responsible Party):
Angelique Spoelstra-de Man, VU University Medical Center

Brief Summary:

Only half of the patients suffering from cardiac arrest arrive at the hospital alive. Of these survivors, more than 50% will still die or remain severely disabled. During cardiac arrest ischemia causes damage to the vital organs, especially the brain. When with return of spontaneous circulation oxygen is re-offered to the ischemic organs, massive amounts of reactive oxygen species (ROS) are produced. These ROS can further increase the damage to the myocardium and brain (reperfusion injury). Vitamin C is the primary circulating antioxidant. It scavenges free radicals and reduces the production of ROS. In a recent study we demonstrated that vitamin C plasma levels are deficient in ~60% of the patients after cardiac arrest, probably due to massive consumption. Vitamin C deficiency reduces the protection against oxidative stress. Intravenous supplementation is needed to restore deficiency and the antioxidative effect of vitamin C is much more potent if it is administered in a supraphysiological dose (≥ 3 g per day). Its strong antioxidative effect may reduce damage to the circulation and to brain, heart and other organs. Beneficial effects of high dose i.v. vitamin C after cardiac arrest have been demonstrated in preclinical studies, but not in patients.

The investigators hypothesize that vitamin C can reduce organ damage, especially cerebral injury, if administered for a short period as a high i.v. dose during the very early phase of reperfusion after cardiac arrest.

Objectives:

  • To determine whether an early high dose i.v. vitamin C can improve organ function, especially neurological outcome, in patients after cardiac arrest
  • To explore the optimal dosing regimen for high dose i.v. vitamin C
  • To investigate in vitro the difference in effect of plasma obtained from post cardiac arrest patients treated with placebo, 3 gr/day or 10 gr/day vitamin C on endothelial cell viability and underlying oxidative pathways.

Condition or disease Intervention/treatment Phase
Cardiac Arrest Drug: Vitamin C Drug: Thiamine Drug: Placebos Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

In this multicentre, placebo controlled double-blind randomized clinical trial patients will be recruited from the Intensive Care Units of 8 hospitals.

270 comatose patients suffering an out-of-hospital cardiac arrest with ventricular fibrillation/tachycardia as first registered cardiac rhythm and EMV-score ≤8 will be included.

As soon as possible patients will be randomly allocated to one of 3 treatment groups of 90 patients each and vitamin C or placebo will be started for 96 hours. Group 1 will be treated with placebo, group 2 with 2 times a day a bolus of 1.5 gr vitamin C and group 3 with 2 times a day a bolus of 5 gr vitamin C.

All patients will receive thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Early High-dose Vitamin C in Post-cardiac Arrest Syndrome
Actual Study Start Date : October 7, 2019
Estimated Primary Completion Date : June 1, 2022
Estimated Study Completion Date : June 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo group
Group 1 will be treated with placebos for 4 days. All patients will receive Thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate
Drug: Thiamine
All patients will receive thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate.

Drug: Placebos
One group receives a placebo.

Active Comparator: Vitamin C - 3 gr/day
Group 2 will be treated with 1.5 gr Vitamin C b.i.d. (3 gr/day) for 4 days. All patients will receive Thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate
Drug: Vitamin C
Vitamine C will be administered intravenously as ascorbic acid (ascorbinezuur CF 100 mg/ml, Centrafarm BV, Etten Leur, Netherlands).
Other Name: Ascorbic acid

Drug: Thiamine
All patients will receive thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate.

Active Comparator: Vitamin C - 10 gr/day
Group 3 will be treated with 5 gr Vitamin C b.i.d. (10 gr/day) for 4 days. All patients will receive Thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate
Drug: Vitamin C
Vitamine C will be administered intravenously as ascorbic acid (ascorbinezuur CF 100 mg/ml, Centrafarm BV, Etten Leur, Netherlands).
Other Name: Ascorbic acid

Drug: Thiamine
All patients will receive thiamine 200 mg q 12 hourly for 4 days to limit the conversion of vitamin C to oxalate.




Primary Outcome Measures :
  1. The delta (Δ) Sequential Organ Failure Assessment (SOFA) score [ Time Frame: 96 hours ]
    ΔSOFA score is defined as the difference between SOFA admission and SOFA at 96 hours (46). Death at 96-hours will be counted as the maximum SOFA score (24 points).


Secondary Outcome Measures :
  1. Maximal Glasgow Coma Score [ Time Frame: At 96-h and after weaning of sedation ]

    Neurological outcome. The Glasgow Coma Scale (GCS) is the most common scoring system used to describe the level of consciousness. The GCS measures the following functions:

    Eye opening (E): 4 = spontaneous, 3 = to sound, 2 = to pressure, 1 = none.

    Verbal response (V): 5 = orientated, 4 = confused, 3 = words, but not coherent, 2 = sounds, but no words, 1 = none.

    Motor response (M): 6 = obeys command, 5 = localizing, 4 = normal flexion, 3 = abnormal flexion, 2 = extension, 1 = none.


  2. Cerebral Performance Categories [ Time Frame: At 30 and 180 days ]
    Neurological outcome after cardiac arrest. CPC 1: Good cerebral performance (normal life) CPC 2: Moderate cerebral disability (disability but independent) CPC 3: Severe cerebral disability (conscious but disabled and dependent) CPC 4: Coma or vegetative state (unconscious) CPC 5: Brain death

  3. Modified Rankin Scale [ Time Frame: At 30 and 180 days ]

    Neurological outcome. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms to death.

    0 - No symptoms.

    1. - No significant disability. Able to carry out all usual activities, despite some symptoms.
    2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
    3. - Moderate disability. Requires some help, but able to walk unassisted.
    4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
    5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
    6. - Dead.

  4. extended Glasgow Outcome Scale [ Time Frame: At 30 and 180 days ]

    Neurological outcome. The Glasgow Outcome Scale (GOS) is a global scale for functional outcome that rates patient status into one of five categories: Dead, Vegetative State, Severe Disability, Moderate Disability or Good Recovery. The Extended GOS (GOSE) provides more detailed categorization into eight categories by subdividing the categories of severe disability, moderate disability and good recovery into a lower and upper category: the scale runs from 1-8.

    1. Death
    2. Vegetative state
    3. Lower severe disability
    4. Upper severe disability
    5. Lower moderate disability
    6. Upper moderate disability
    7. Lower good recovery
    8. Upper good recovery.

  5. HUI-3 questionnaire [ Time Frame: At 30 and 180 days ]
    Neurological outcome

  6. Neuron-specific enolase [ Time Frame: At day 1, 2 and 3 ]
    Neurological outcome

  7. Intensive Care (IC)-stay [ Time Frame: The total length of IC-stay will be determined from the date of ICU admission until the patient is discharged from the Intensive Care Unit or the date of death from any cause, assessed up to 1 year after the first day of admission. ]
    Clinical parameter

  8. Hospital-stay [ Time Frame: The total length of hospital-stay will be determined from the date of ICU admission until the patient is discharged from the hospital or the date of death from any cause assessed up to 1 year after the first day of admission. ]
    Clinical parameter

  9. Mortality [ Time Frame: 30-day ]
    Clinical parameter

  10. Mortality [ Time Frame: 180-day ]
    Clinical parameter

  11. Duration of vasopressor support [ Time Frame: When the patient is discharged from the Intensive Care or when the patient past away, the total duration of vasopressor support will be determined, assessed up to 1 year after the first day of admission. ]
    Clinical parameter

  12. Troponin and CK-MB [ Time Frame: Maximum day 1 ]
    Myocardial injury

  13. Lung injury score [ Time Frame: Daily for 1 week ]
    Organ injury

  14. Ventilation time [ Time Frame: Total ventilation time during ICU stay will be determined when the patient is discharged from the ICU or when the patient past away from any cause, assessed up to 1 year after the first day of admission. ]
  15. Renal function [ Time Frame: eGFR will be measured daily till discharge from the ICU, assessed up to 1 year after the first day of admission. ]
    estimated Glomerular Filtration Rate (eGFR)

  16. Renal function [ Time Frame: Serum creatinine will be measured daily till discharge from the ICU, assessed up to 1 year after the first day of admission. ]
    serum creatinine

  17. Need of renal replacement therapy [ Time Frame: Need of renal replacement therapy during hospital admission will be determined at hospital discharge, assessed up to 1 year after the first day of admission. ]
    Yes or no

  18. Medical Research Council score [ Time Frame: Day 3, 5 and 7 ]
    IC-acquired weakness

  19. CAM-ICU score [ Time Frame: Daily for 1 week ]
    Delirium

  20. ICDSC score [ Time Frame: Daily for 1 week ]
    Delirium

  21. C-reactive protein [ Time Frame: Daily for 1 week ]
    Inflammation

  22. F2-isoprostanes [ Time Frame: Daily from day 1 to 7 ]
    Oxidative stress parameters

  23. Oxidation-reduction potential [ Time Frame: Day 1, 3 and 5 ]
    Oxidative stress parameters

  24. Antioxidant capacity [ Time Frame: Day 1, 3 and 5 ]
    Oxidative stress parameters

  25. Vitamin C plasma concentrations [ Time Frame: Daily from day 1 to 5 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • An out-of-hospital cardiac arrest with return of spontaneous circulation
  • Ventricular fibrillation or ventricular tachycardia as first registered cardiac rhythm
  • Glasgow Coma Scale (GCS)-score ≤8.

Exclusion Criteria:

  • Patients with pre-existent terminal renal insufficiency
  • Known glucose 6-phosphate dehydrogenase deficiency (risk of hemolysis)
  • History of urolithiasis, oxalate nephropathy or hemochromatosis
  • Treatment limitations.

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): NCT03509662


Contacts
Layout table for location contacts
Contact: Sander Rozemeijer, MSc +31204443924 s.rozemeijer@vumc.nl
Contact: Secretory Intensive Care +31204443697

Locations
Layout table for location information
Netherlands
VU Medical Center Recruiting
Amsterdam, Noord-Holland, Netherlands, 1081 HV
Sponsors and Collaborators
VU University Medical Center
Gelderse Vallei Hospital
Sint Franciscus Gasthuis
Tergooiziekenhuizen
Amphia Hospital
Erasmus Medical Center
Noordwest Ziekenhuisgroep
Maasstad Hospital
OLVG
Investigators
Layout table for investigator information
Study Director: Angelique ME Spoelstra-de Man, Dr. VU University Medical Center

Publications:
Beesems JA, Stieglis R, Koster RW. Reanimatie buiten het ziekenhuis in Noord-Holland en twente: resultaten ARREST-onderzoek 2006-2011. 2012.
Grooth HJ, Spoelstra-de Man AME, Oudemans-van Straaten HM. Early plasma Vitamin C concentration, organ dysfunction and ICU mortality. Intensive Care Medicine 2014; 40 (10 (Suppl 1)): S199.

Layout table for additonal information
Responsible Party: Angelique Spoelstra-de Man, M.D., Ph.D., VU University Medical Center
ClinicalTrials.gov Identifier: NCT03509662    
Other Study ID Numbers: NL63681.029.17
First Posted: April 26, 2018    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Angelique Spoelstra-de Man, VU University Medical Center:
Vitamin C
Cardiac Arrest
Post-cardiac arrest syndrome
Oxidative stress
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Arrest
Heart Diseases
Cardiovascular Diseases
Vitamins
Ascorbic Acid
Thiamine
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Vitamin B Complex