出境医 / 临床实验 / VitamIn and oXygen Interventions and Cardiovascular Events (VIXIE)

VitamIn and oXygen Interventions and Cardiovascular Events (VIXIE)

Study Description
Brief Summary:
This study examines the risks and benefits of antioxidants and normal versus high inspiratory oxygen fraction during anaesthesia.

Condition or disease Intervention/treatment Phase
Postoperative Cardiac Complication Drug: Oxygen Drug: Antioxidants Phase 4

Detailed Description:

Adult patients with risk factors for developing postoperative cardiac complications will be enrolled in the study. The patients will be randomised to receiving antioxidants or placebo perioperatively and 30% or 80% inspiratory oxygen concentration during anaesthesia and 2 hours postoperatively. The primary outcome is MINS (myocardial injury after non-cardiac surgery). The antioxidants are ascorbic acid (vitamin C) 3 grams intravenously preoperatively and N-acetylcysteine 100 milligrams/kilogram body weight intravenous infusion for 4 hours, starting at the same time as anaesthesia.

The study is a long-term follow-up study of the risk of mortality, MI and readmissions performed at 1 year after inclusion of the last patient. Two other follow-up studies are planned: One investigation of ischaemic troponin elevations defined as peak troponin levels above the internationally defined thresholds without extracardiac causes; another investigating the intervention effects in the subgroup of patients undergoing vascular surgery with specific emphasis on episodes of intraoperative hypotension within the following thresholds: MAP below 70 mmHg, 65 mmHg, 60 mmHg and 55 mmHg.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Hyperoxia and Antioxidants During Major Non-cardiac Surgery and Risk of Cardiovascular Complications, a Blinded 2x2 Factorial Randomised Clinical Trial
Actual Study Start Date : April 6, 2018
Actual Primary Completion Date : March 1, 2020
Actual Study Completion Date : March 24, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: 1 Drug: Oxygen
80% versus 30% inspiratory oxygen concentration

Drug: Antioxidants
Antioxidants versus placebo
Other Names:
  • Ascorbic acid
  • N-acetylcysteine

Experimental: 2 Drug: Oxygen
80% versus 30% inspiratory oxygen concentration

Drug: Antioxidants
Antioxidants versus placebo
Other Names:
  • Ascorbic acid
  • N-acetylcysteine

Outcome Measures
Primary Outcome Measures :
  1. Myocardial injury after non-cardiac surgery (MINS) [ Time Frame: 30 days ]
    Troponin measurement the first 3 postoperative days. Assessed by area under the curve.


Secondary Outcome Measures :
  1. Mortality [ Time Frame: During the study period until completion of last visit of last patient ]
    Assessed as time to event analysis

  2. Non-fatal myocardial infarction [ Time Frame: During the study period until completion of last visit of last patient ]
    Assessed as time to event analysis

  3. Non-fatal Serious Adverse Event [ Time Frame: During the study period until completion of last visit of last patient ]
    Assessed as time to event analysis


Other Outcome Measures:
  1. Surgical site infection [ Time Frame: Assessed at postoperative day 30 ]
    Infection in surgical area as defined by the Center for Disease Control

  2. Pneumonia [ Time Frame: Assessed at postoperative day 30 ]
    Pneumonia as defined by the Center for Disease Control

  3. Sepsis [ Time Frame: Assessed at postoperative day 30 ]
    Sepsis as defined by the joint task force by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine

  4. Acute respiratory failure [ Time Frame: Assessed at postoperative day 30 ]
    Acute respiratory failure defined as the need for controlled ventilation or oxygen saturation of 900% or less despite of oxygen therapy

  5. Acute kidney injury [ Time Frame: Assessed at postoperative day 30 ]
    Acute kidney injury as defined Kidney Disease Improving Global Outcomes guidelines


Eligibility Criteria
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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

All of the listed criteria (1.-4.) must be met.

  1. Age 45 years or above
  2. Elective or acute surgery in general anaesthesia
  3. Scheduled for abdominal, orthopaedic, or vascular surgery with expected surgery duration of one hour or more.
  4. Fulfil any 1 of the following 5 criteria:

    1. - History of coronary artery disease including angina
    2. - History of stroke
    3. - Undergoing vascular surgery
    4. - History of peripheral arterial disease
    5. - Any 2 of the following 8 criteria: i. Acute surgery ii. Current or previous daily smoking iii. History of hypertension iv. Diabetes mellitus requiring medical treatment v. History of transient cerebral ischemia vi. Plasma creatinine >175 µM vii. Age 70 years or above viii. History of congestive heart failure

Exclusion criteria:

  1. Surgery within 30 days prior to operation
  2. Arterial oxygen saturation below 90% without oxygen supplementation
  3. Inability to give informed consent
  4. Drug allergy towards any of the drugs involved in the trial
  5. Previous treatment with bleomycin
  6. Pregnancy
Contacts and Locations

Locations
Layout table for location information
Denmark
Abdominalcentret, Rigshospitalet
Copenhagen, Denmark, 2100
HovedOrtoCentret, Rigshospitalet
Copenhagen, Denmark, 2100
Bispebjerg and Frederiksberg Hospital, University of Copenhagen
Copenhagen, Denmark
Herlev Hospital
Herlev, Denmark
Sponsors and Collaborators
University Hospital Bispebjerg and Frederiksberg

Tracking Information
First Submitted Date  ICMJE March 21, 2018
First Posted Date  ICMJE April 11, 2018
Last Update Posted Date April 30, 2021
Actual Study Start Date  ICMJE April 6, 2018
Actual Primary Completion Date March 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2018)
Myocardial injury after non-cardiac surgery (MINS) [ Time Frame: 30 days ]
Troponin measurement the first 3 postoperative days. Assessed by area under the curve.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
  • Mortality [ Time Frame: During the study period until completion of last visit of last patient ]
    Assessed as time to event analysis
  • Non-fatal myocardial infarction [ Time Frame: During the study period until completion of last visit of last patient ]
    Assessed as time to event analysis
  • Non-fatal Serious Adverse Event [ Time Frame: During the study period until completion of last visit of last patient ]
    Assessed as time to event analysis
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: May 15, 2018)
  • Surgical site infection [ Time Frame: Assessed at postoperative day 30 ]
    Infection in surgical area as defined by the Center for Disease Control
  • Pneumonia [ Time Frame: Assessed at postoperative day 30 ]
    Pneumonia as defined by the Center for Disease Control
  • Sepsis [ Time Frame: Assessed at postoperative day 30 ]
    Sepsis as defined by the joint task force by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine
  • Acute respiratory failure [ Time Frame: Assessed at postoperative day 30 ]
    Acute respiratory failure defined as the need for controlled ventilation or oxygen saturation of 900% or less despite of oxygen therapy
  • Acute kidney injury [ Time Frame: Assessed at postoperative day 30 ]
    Acute kidney injury as defined Kidney Disease Improving Global Outcomes guidelines
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE VitamIn and oXygen Interventions and Cardiovascular Events
Official Title  ICMJE Hyperoxia and Antioxidants During Major Non-cardiac Surgery and Risk of Cardiovascular Complications, a Blinded 2x2 Factorial Randomised Clinical Trial
Brief Summary This study examines the risks and benefits of antioxidants and normal versus high inspiratory oxygen fraction during anaesthesia.
Detailed Description

Adult patients with risk factors for developing postoperative cardiac complications will be enrolled in the study. The patients will be randomised to receiving antioxidants or placebo perioperatively and 30% or 80% inspiratory oxygen concentration during anaesthesia and 2 hours postoperatively. The primary outcome is MINS (myocardial injury after non-cardiac surgery). The antioxidants are ascorbic acid (vitamin C) 3 grams intravenously preoperatively and N-acetylcysteine 100 milligrams/kilogram body weight intravenous infusion for 4 hours, starting at the same time as anaesthesia.

The study is a long-term follow-up study of the risk of mortality, MI and readmissions performed at 1 year after inclusion of the last patient. Two other follow-up studies are planned: One investigation of ischaemic troponin elevations defined as peak troponin levels above the internationally defined thresholds without extracardiac causes; another investigating the intervention effects in the subgroup of patients undergoing vascular surgery with specific emphasis on episodes of intraoperative hypotension within the following thresholds: MAP below 70 mmHg, 65 mmHg, 60 mmHg and 55 mmHg.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Postoperative Cardiac Complication
Intervention  ICMJE
  • Drug: Oxygen
    80% versus 30% inspiratory oxygen concentration
  • Drug: Antioxidants
    Antioxidants versus placebo
    Other Names:
    • Ascorbic acid
    • N-acetylcysteine
Study Arms  ICMJE
  • Experimental: 1
    Interventions:
    • Drug: Oxygen
    • Drug: Antioxidants
  • Experimental: 2
    Interventions:
    • Drug: Oxygen
    • Drug: Antioxidants
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 10, 2018)
600
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 24, 2020
Actual Primary Completion Date March 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

All of the listed criteria (1.-4.) must be met.

  1. Age 45 years or above
  2. Elective or acute surgery in general anaesthesia
  3. Scheduled for abdominal, orthopaedic, or vascular surgery with expected surgery duration of one hour or more.
  4. Fulfil any 1 of the following 5 criteria:

    1. - History of coronary artery disease including angina
    2. - History of stroke
    3. - Undergoing vascular surgery
    4. - History of peripheral arterial disease
    5. - Any 2 of the following 8 criteria: i. Acute surgery ii. Current or previous daily smoking iii. History of hypertension iv. Diabetes mellitus requiring medical treatment v. History of transient cerebral ischemia vi. Plasma creatinine >175 µM vii. Age 70 years or above viii. History of congestive heart failure

Exclusion criteria:

  1. Surgery within 30 days prior to operation
  2. Arterial oxygen saturation below 90% without oxygen supplementation
  3. Inability to give informed consent
  4. Drug allergy towards any of the drugs involved in the trial
  5. Previous treatment with bleomycin
  6. Pregnancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03494387
Other Study ID Numbers  ICMJE VIXIE2018
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cecilie Petersen, University Hospital Bispebjerg and Frederiksberg
Study Sponsor  ICMJE University Hospital Bispebjerg and Frederiksberg
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University Hospital Bispebjerg and Frederiksberg
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP