VIXIE: VitamIn and oXygen Interventions and Cardiovascular Events

Sponsor

University Hospital Bispebjerg and Frederiksberg (Other)

Overall Status

Completed

CT.gov ID

NCT03494387

Collaborator

(none)

600

Enrollment

Locations

Arms

23.6

Actual Duration (Months)

150

Patients Per Site

6.4

Patients Per Site Per Month

Study Details

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

Study Type:

Interventional

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 :

Apr 6, 2018

Actual Primary Completion Date :

Mar 1, 2020

Actual Study Completion Date :

Mar 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

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

Myocardial injury after non-cardiac surgery (MINS) [30 days]
Troponin measurement the first 3 postoperative days. Assessed by area under the curve.

Secondary Outcome Measures

Mortality [During the study period until completion of last visit of last patient]
Assessed as time to event analysis
Non-fatal myocardial infarction [During the study period until completion of last visit of last patient]
Assessed as time to event analysis
Non-fatal Serious Adverse Event [During the study period until completion of last visit of last patient]
Assessed as time to event analysis

Other Outcome Measures

Surgical site infection [Assessed at postoperative day 30]
Infection in surgical area as defined by the Center for Disease Control
Pneumonia [Assessed at postoperative day 30]
Pneumonia as defined by the Center for Disease Control
Sepsis [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 [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 [Assessed at postoperative day 30]
Acute kidney injury as defined Kidney Disease Improving Global Outcomes guidelines

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Abdominalcentret, Rigshospitalet	Copenhagen	Denmark	2100
2	HovedOrtoCentret, Rigshospitalet	Copenhagen	Denmark	2100
3	Bispebjerg and Frederiksberg Hospital, University of Copenhagen	Copenhagen	Denmark
4	Herlev Hospital	Herlev	Denmark