Clinical trial NCT03494387: VitamIn and oXygen Interventions and Cardiovascular Events
Official title: Hyperoxia and Antioxidants During Major Non-cardiac Surgery and Risk of Cardiovascular Complications, a Blinded 2x2 Factorial Randomised Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postoperative Cardiac Complication
Keywords: Antioxidant
Hyperoxia
Troponin
MINS
Ascorbic acid
N-acetylcysteine
Lead sponsor: University Hospital Bispebjerg and Frederiksberg
Sponsor class: OTHER
First posted: 2018-04-11
Enrollment: 600
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: Myocardial injury after non-cardiac surgery (MINS)
timeFrame: 30 days
Secondary outcomes:
measure: Mortality
timeFrame: During the study period until completion of last visit of last patient
measure: Non-fatal myocardial infarction
timeFrame: During the study period until completion of last visit of last patient
measure: Non-fatal Serious Adverse Event
timeFrame: During the study period until completion of last visit of last patient
Other outcomes:
measure: Surgical site infection
timeFrame: Assessed at postoperative day 30
measure: Pneumonia
timeFrame: Assessed at postoperative day 30
measure: Sepsis
timeFrame: Assessed at postoperative day 30
measure: Acute respiratory failure
timeFrame: Assessed at postoperative day 30
measure: Acute kidney injury
timeFrame: Assessed at postoperative day 30
Locations:
city: Copenhagen
country: Denmark
facility: Abdominalcentret, Rigshospitalet
city: Copenhagen
country: Denmark
facility: HovedOrtoCentret, Rigshospitalet
city: Copenhagen
country: Denmark
facility: Bispebjerg and Frederiksberg Hospital, University of Copenhagen
city: Herlev
country: Denmark
facility: Herlev Hospital
Study officials:
References: