VitamIn and oXygen Interventions and Cardiovascular Events

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

Detailed Description
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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.

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

Conditions
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Postoperative Cardiac Complication

Intervention / Treatment
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* Drug: Oxygen
* Drug: Antioxidants


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: All of the listed criteria (1.-4.) must be met. Age 45 years or above Elective or acute surgery in general anaesthesia Scheduled for abdominal, orthopaedic, or vascular surgery with expected surgery duration of one hour or more. Fulfil any 1 of the following 5 criteria: - History of coronary artery disease including angina - History of stroke - Undergoing vascular surgery - History of peripheral arterial disease - 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: Surgery within 30 days prior to operation Arterial oxygen saturation below 90% without oxygen supplementation Inability to give informed consent Drug allergy towards any of the drugs involved in the trial Previous treatment with bleomycin Pregnancy

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Oxygen<br>* 80% versus 30% inspiratory oxygen concentration<br>Drug: Antioxidants<br>* Antioxidants versus placebo<br>* Other names: N-acetylcysteine;|
| Experimental: 2<br> | Drug: Oxygen<br>* 80% versus 30% inspiratory oxygen concentration<br>Drug: Antioxidants<br>* Antioxidants versus placebo<br>* Other names: N-acetylcysteine;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antioxidant, Hyperoxia, Troponin, MINS, Ascorbic acid, N-acetylcysteine