Air Verses Oxygen In myocarDial Infarction Study (AVOID)
The AVOID (Air Verses Oxygen In myocardial infarction) trial is designed to determine if the withholding of routine oxygen therapy in patients with acute heart attack leads to reduced heart damage compared to the current practice of routine inhaled oxygen for all patients.
There is evidence supporting and refuting the current practice of providing oxygen to all patients with acute heart attack. A recent summary of clinical trials suggested that oxygen may increase the degree of heart damage during heart attack. It also highlighted that the few trials into oxygen therapy were performed before the use of modern medications and procedures to treat heart attack and that further studies were urgently needed, using contemporary practices.
A total of 334 patients will participate in this randomized controlled trial. Patients in this study will receive the best current management and care for their condition. Patients will be randomized to routine pre hospital care with oxygen therapy vs pre hospital care without oxygen therapy. Patients will then receive standard hospital care, aside from allocated oxygen or no oxygen therapy. The primary outcome measure of heart damage will be investigated using routine blood tests. With additional information gathered from other aspects of routine heart care including coronary angiogram, electrocardiograms and complications of hospital stay. Patients will be followed up at 6 months to determine any longer term effects of treatment.
Acute Myocardial Infarction
Coronary Artery Disease
Other: Withholding oxygen in uncomplicated patients with STEMI
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomised Controlled Trial of Oxygen Therapy in Acute Myocardial Infarction (AVOID - Air Verses Oxygen In myocarDial Infarction Study)|
- Myocardial infarct size [ Time Frame: At 72 hours post infarct ] [ Designated as safety issue: No ]
The primary end-point for the study will be infarct size at hospital discharge which will be ascertained by the routinely collected cardiac biomarkers during hospital admission such as cardiac troponin I (cTnI) and creatine kinase (CK)Infarct size will be evaluated via blood test on admission and then 6 hourly tests for 48 hours and 12 hourly measurements between 48 hours and 72 hours. Infarct size will be measured by:
- Mean and peak cTnI
- Mean and peak CK
- The area under the curve of CK and cTnI release over the first 72 hours of reperfusion.
- ST segment resolution [ Time Frame: 60 minutes post reperfusion ] [ Designated as safety issue: No ]
- TIMI Flow [ Time Frame: At completion of coronary intervention procedure ] [ Designated as safety issue: No ]TIMI - Thrombolysis in Myocardial infarction score
- Survival to hospital discharge [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
- MACE [ Time Frame: 6 months ] [ Designated as safety issue: No ]Major Adverse Cardiac Events (MACE): Death, MI, re-hospitalization measured at 6 months
- myocardial salvage [ Time Frame: 4 days and 6 months ] [ Designated as safety issue: No ]Magnetic resonance imaging (MRI) measurement of infarct size as percent of area at risk determined with T2-weighted MRI (in small sub set of patients) at day 4 and repeated at 6 months.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
For patients randomised to Oxygen Therapy:
Other: Withholding oxygen in uncomplicated patients with STEMI
No oxygen pre-hospital or in-hospital unless the oxygen saturation falls below 94% in which case oxygen will be administered via nasal cannulae (4L/min) or Hudson mask (8L/min) and titrated to achieve oxygen saturation of 94%
For patients allocated to No Oxygen:
Oxygen administered via Hudson mask at 8/l min
Hide Detailed Description
Coronary artery disease (CAD) is a leading cause of morbidity and mortality in Australia. In particular, many patients with CAD present with ST-elevation myocardial infarction (STEMI) as a result of acute thrombotic coronary artery occlusion. The optimal treatment for patients presenting with STEMI is reperfusion therapy either with primary percutaneous coronary intervention (PCI) or administration of a thrombolytic drug.
Current guidelines recommend additional treatments for patients with STEMI prior to reperfusion therapy, such as oxygen, aspirin and nitrates. Whilst there is supportive evidence from clinical trials for the administration of aspirin and nitrates, there is no data from prospective, randomised, controlled clinical trials to support the use of routine supplemental oxygen.
For many years, the administration of supplemental oxygen has been considered beneficial for the treatment of patients with acute myocardial infarction largely based on experimental data. For example, in a laboratory study, anaesthetised dogs underwent coronary artery occlusion and were then administered either 21% oxygen, 40% oxygen or 100% oxygen. In the 40% oxygen group, there was decreased myocardial injury and infarct size compared with the air or 100% oxygen groups.
In another laboratory study, two groups of dogs underwent 90 minutes of coronary occlusion followed by 72 hours of reperfusion. One group received 100% inspired oxygen from 20 minutes before reperfusion and three hours after reperfusion whereas the air group received room air. The infarct size in the oxygen group was reduced by 38% and left ventricular ejection fraction was improved compared with the dogs receiving room air. This data suggests that high concentrations of inspired oxygen may be of benefit in acute myocardial infarction followed by reperfusion therapy.
In order to increase myocardial oxygen delivery further, recent clinical studies have examined the role of novel techniques for additional oxygen delivery to the ischemic myocardium during reperfusion. In a clinical trial testing the role of hyperbaric oxygen (HBO) in myocardial infarction, 112 patients with STEMI were allocated to either HBO or usual supplemental oxygen (40% by mask or 6L/min by nasal prongs) during thrombolysis. There was no significant difference between the groups in creatinine kinase levels at 24 hours or left ventricle ejection fraction (LVEF) on discharge. Overall, there was no overall benefit with this approach found in this study.
In a clinical trial testing coronary artery reperfusion with hyperoxic blood during reperfusion, 269 patients with acute AMI undergoing PCI were randomly assigned to receive hyperoxemic blood reperfusion or normoxemic blood reperfusion by catheter into the area of reperfused myocardium. At 30 days, there was no significant difference in the infarct size, ST-segment resolution, or regional wall motion score. Although improvement in cardiac function was seen in patients with anterior MI who were reperfused within 6 hours, this finding was a post-hoc analysis.
There is increasing data that suggests that oxygen administration before and during reperfusion in patients with STEMI may be harmful.
A meta-analysis of all studies of hyperoxic myocardial reperfusion found that hyperoxia caused a significant reduction in coronary blood flow, an increase in coronary vascular resistance and a significant reduction in myocardial oxygen consumption. This data appears to suggest that supplemental oxygen may be harmful.
There is other laboratory and clinical evidence to suggest that oxygen administration may be harmful to patients with STEMI. For example, the inhalation of oxygen in high concentration has been investigated in 50 patients with acute myocardial infarction. This resulted in adverse effects including a fall in cardiac output, a rise in blood pressure and an increase systemic vascular resistance.
There have been two prospective, controlled trials of supplemental oxygen compared with no supplemental oxygen in patients with myocardial infarction.
In a double-blind, randomised in-hospital study, two-hundred patients with myocardial infarction were allocated to receive supplemental oxygen or air administered by face mask for the initial 24 hours in hospital. The two groups were comparable at baseline. There was no significant difference in mortality, incidence of arrhythmias or use of analgesics between the groups. There was a higher incidence of sinus tachycardia in the patients given oxygen. This study suggested that there was no benefit from the routine administration of oxygen in uncomplicated myocardial infarction.
In a second study, 50 patients were allocated to either supplemental oxygen or room air. The main outcome measure was the requirement for analgesia with 16 of 22 patients (72.7%) in the oxygen group using opiates for pain relief compared with 18 of 20 patients (90%) in the air group. This study did not report mortality rate.
In a third study conducted in Russia, 137 patients were allocated to either supplemental oxygen (4-6L/Min) or air. Complications including heart failure, pericarditis and rhythm disorders occurred less frequently in the air group (Risk ratio 0.45: 95% CI 0.22 to 0.94). One patient out of 58 died in the oxygen group and none out of 79 participants in the air group.
A meta-analysis analysed the outcomes in the 387 patients included in these three studies. The pooled risk ratio of death for patients allocated to oxygen administration was 2.88 (95% CI 0.88 to 9.39) in an intention-to-treat analysis and 3.03 (95% CI 0.93 to 9.83) in patients with confirmed myocardial infarction. While suggestive of harm, the small number of deaths recorded meant that this finding did not reach statistical significance. Pain was measured by analgesic use and the pooled risk ratio for decreased use of analgesics in the oxygen group was 0.97 (95% CI 0.78 to 1.20).
Given the lack of data of efficacy, European guidelines for the management of acute coronary syndromes do not include a recommendation for supplemental oxygen17. Whilst the recent American Heart Association guidelines for the management of acute coronary syndrome do recommend oxygen, they note that there is no clinical trial evidence to support this recommendation.
In summary, whilst there is some laboratory evidence of benefit for supplemental oxygen during STEMI and reperfusion, the available clinical data suggests that oxygen may be harmful. Since oxygen is currently recommended in the treatment of acute coronary syndromes, prospective clinical trials comparing supplemental oxygen with no supplemental oxygen in this condition are required.
Ambulance Victoria is uniquely placed to undertake this research. The Mobile Intensive Care Ambulances (MICA) of Ambulance Victoria are equipped with 12 lead ECG capability and pulse-oximetry monitors. In Melbourne, MICA attends approximately 400 STEMI patients per year.
We therefore propose to undertake a randomised, controlled trial comparing supplemental oxygen therapy with air in patients without hypoxia who present with STEMI to determine the effect on the size of the myocardial infarct at hospital discharge.
|Contact: Dion Stub, MBBS||613 9076 firstname.lastname@example.org|
|Contact: Stephen Bernard, MBBS MDemail@example.com|
|Melbourne, Victoria, Australia, 3108|
|Principal Investigator: Karen Smith, BSc PhD|
|Melbourne, Victoria, Australia, 3004|
|Principal Investigator: Anthony Dart, BA BM BCh DPhil|
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|Principal Investigator: Omar Farouque, MBBS PhD|
|Box Hill Hospital||Recruiting|
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|Royal Melbourne Hospital||Not yet recruiting|
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|Principal Investigator: Leeanne Grigg, MBBS|
|Monash Medical Centre||Recruiting|
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|Principal Investigator: Ian Meredith, BSc MBBS PhD|
|Northern Hospital||Not yet recruiting|
|Melbourne, Victoria, Australia, 3076|
|Principal Investigator: William Van Gaal, MBBS MSc|
|Western Hospital||Not yet recruiting|
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|Principal Investigator: Yean Lim, MBBS PhD|
|St Vincents Hospital||Not yet recruiting|
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|Principal Investigator: Robert Whitbourn, MBBS BSc MD|
|Principal Investigator:||Stephen Bernard, MBBS MD||Alfred Hospital, Monash University, Ambulance Victoria|
|Principal Investigator:||Karen Smith, BSc PhD||Ambulance Victoria, Monash University|
|Study Director:||Dion Stub, MBBS||Alfred Hospital, Baker IDI Institute, Monash University|
|Study Director:||Ian Meredith, BSc MBBS PhD||Southern Health, Monash University|
|Study Director:||Michael Stephenson, RN BA Grad Dip||Ambulance Victoria|
|Study Director:||Janet Bray, RN PhD||Ambulance Victoria|
|Study Director:||Bill Barger, ADHS||Ambulance Victoria|
|Study Director:||Ian Jarvie||Ambulance Victoria|
|Study Director:||David Kaye, MBBS PhD||Alfred Hospital, Baker IDI Institute, Monash University|
|Study Director:||Peter Cameron, MBBS MD||Alfred Hospital, Monash University|