VitamIn and oXygen Interventions and Cardiovascular Events (VIXIE)

Hyperoxia and Antioxidants During Major Non-cardiac Surgery and Risk of Cardiovascular Complications, a Blinded 2x2 Factorial Randomised Clinical Trial

This study examines the risks and benefits of antioxidants and normal versus high inspiratory oxygen fraction during anaesthesia.

Study Overview

• Status: Completed
• Conditions: Postoperative Cardiac Complication
• Intervention / Treatment: Drug: Oxygen; Drug: Antioxidants

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: Interventional
• Enrollment (Actual): 600
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Abdominalcentret, Rigshospitalet
  • Copenhagen, Denmark, 2100
    • HovedOrtoCentret, Rigshospitalet
  • Copenhagen, Denmark
    • Bispebjerg and Frederiksberg Hospital, University of Copenhagen
  • Herlev, Denmark
    • Herlev Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Oxygen; 80% versus 30% inspiratory oxygen concentration; Drug: Antioxidants; Antioxidants versus placebo; Other Names: N-acetylcysteine; Ascorbic acid
Experimental: 2	Drug: Oxygen; 80% versus 30% inspiratory oxygen concentration; Drug: Antioxidants; Antioxidants versus placebo; Other Names: N-acetylcysteine; Ascorbic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial injury after non-cardiac surgery (MINS)	Troponin measurement the first 3 postoperative days. Assessed by area under the curve.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Assessed as time to event analysis	During the study period until completion of last visit of last patient
Non-fatal myocardial infarction	Assessed as time to event analysis	During the study period until completion of last visit of last patient
Non-fatal Serious Adverse Event	Assessed as time to event analysis	During the study period until completion of last visit of last patient

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical site infection	Infection in surgical area as defined by the Center for Disease Control	Assessed at postoperative day 30
Pneumonia	Pneumonia as defined by the Center for Disease Control	Assessed at postoperative day 30
Sepsis	Sepsis as defined by the joint task force by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine	Assessed at postoperative day 30
Acute respiratory failure	Acute respiratory failure defined as the need for controlled ventilation or oxygen saturation of 900% or less despite of oxygen therapy	Assessed at postoperative day 30
Acute kidney injury	Acute kidney injury as defined Kidney Disease Improving Global Outcomes guidelines	Assessed at postoperative day 30

Collaborators and Investigators

• Sponsor: University Hospital Bispebjerg and Frederiksberg

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2018
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 24, 2020

Study Registration Dates

• First Submitted: March 21, 2018
• First Submitted That Met QC Criteria: April 10, 2018
• First Posted (Actual): April 11, 2018

Study Record Updates

• Last Update Posted (Actual): April 30, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: N-acetylcysteine; Antioxidant; Ascorbic acid; Troponin; Hyperoxia; MINS
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hyperoxia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Micronutrients; Respiratory System Agents; Vitamins; Free Radical Scavengers; Expectorants; Acetylcysteine; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: VIXIE2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No