An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction (DETO₂X-AMI)

• Myocardial damage [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3-5 days ] [ Designated as safety issue: No ]
  Myocardial damage assessed by cardiac resonance imaging (CMR), by electrocardiogram, biomarkers and coronary angiography using the index of microvascular resistance (IMR)
• Mortality and morbidity [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3-5 days, at 30 days and 1-year ] [ Designated as safety issue: No ]
  Evaluate mortality during hospital stay, at 30 days and 1-year.
• Heart failure evaluation [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3-5 days ] [ Designated as safety issue: No ]
  Assessment of the degree of heart failure by echocardiography, biomarkers and number of patients needing medical (iv-drugs such as furosemide, nitroglycerine or inotropes) and/or mechanical (CPAP) assistance.
• Health economics [ Time Frame: Health economics will be assessed from first contact with the ambulance service through to the duration of hospital stay, an expected average of 3-5 days ] [ Designated as safety issue: No ]
  Health economics concerning supplemental oxygen treatment from prehospital contact of the emergency service through to hospital discharge

• Myocardial damage [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3-5 days ] [ Designated as safety issue: No ]
  Myocardial damage assessed by cardiac resonance imaging (CMR), by electrocardiogram, biomarkers and coronary angiography using the index of microvascular resistance (IMR)
• Mortality and morbidity [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3-5 days, at 30 days and 1-year ] [ Designated as safety issue: No ]
  Evaluate mortality during hospital stay, at 30 days and 1-year. Perform a predefined metaanalysis including previous randomised studies (Rawles et al, Ukholkina et al, Ranchord et al).
• Heart failure evaluation [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3-5 days ] [ Designated as safety issue: No ]
  Assessment of the degree of heart failure by echocardiography, biomarkers and number of patients needing medical (iv-drugs such as furosemide, nitroglycerine or inotropes) and/or mechanical (CPAP) assistance.
• Health economics [ Time Frame: Health economics will be assessed from first contact with the ambulance service through to the duration of hospital stay, an expected average of 3-5 days ] [ Designated as safety issue: No ]
  Health economics concerning supplemental oxygen treatment from prehospital contact of the emergency service through to hospital discharge

The use of supplemental oxygen in the setting of suspected acute myocardial infarction (AMI) is manifested in international treatment guidelines and established in prehospital and hospital clinical routine throughout the world.

However, to date there is no conclusive evidence from adequately designed and powered trials supporting this practice. Existing data is conflicting and failing to clarify the role of supplemental oxygen in AMI.

The DETO₂X-AMI trial is designed to shed light on this important issue.

AIM:

The aim of the DETO₂X-AMI trial is to evaluate the role of supplemental oxygen delivery in the setting of acute coronary syndrome myocardial infarction including ST-segment elevation myocardial infarction (STEMI), non ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA).

DESIGN:

DETO₂X-AMI is a multicentre, interventional, controlled, randomized registry based clinical trial (RRCT) recruiting 6600 patients at cardiac care facilities which report into the SWEDEHEART registry throughout the whole of Sweden.

The SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry is a nationwide used platform allowing a broad population of all-comers access to the broad registry network which includes:

• RIKS-HIA (nationwide registry where all ischemia cases treated on cardiac intensive care units are registered),
• SCAAR (Swedish Coronary Angiography and Angioplasty Registry where nationwide all coronary angiography and percutaneous coronary intervention (PCI) procedures are registered))
• SEPHIA (nationwide registry for all post AMI follow-up).

All follow-up will be carried out in SWEDEHEART and other national registries such as the national death origin registry (dödsorsaksregister) or the in-patient care registry (slutenvårdsregister). A similar set-up has been successfully used for the TASTE (Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia)trial.

MATERIAL and METHODS:

Patients with normal oxygen saturation (≥90% on pulse oximeter) presenting to the ambulance service or the emergency department (ED) with classical symptoms suggestive of acute coronary syndrome (ACS) and significant ECG changes or elevated cardiac biomarkers (ED) are evaluated for inclusion. If eligible, oral informed consent is obtained by EMD or ED personnel prior to inclusion. Randomization is carried out on the cardiac intensive care unit using a web-based tool as part of registration directly into the national SWEDEHEART registry.

Patients are randomized to either supplemental oxygen delivered by oxymask® (6 L/min) for 12 hours (min 6 hours) or no supplemental O₂. All patients receive standard care according to international ACS guidelines including acute coronary intervention.

Primary endpoint is 1-year all-cause mortality. Secondary endpoints will furthermore evaluate mortality, complications during hospital stay, heart failure (echocardiography, registry), myocardial damage using cardiac resonance imaging (CMR), electrocardiogram, modern biomarkers and coronary angiography and health economics.

Follow-up is carried out according to clinical post AMI routine which includes a standardized registration in the SWEDEHEART registry. Mortality data is obtained from the national death origin registry which is linked to SWEDEHEART.

CONCLUSION:

There is no conclusive evidence from adequately designed and powered trials supporting the routine administration of supplemental oxygen in the setting of suspected AMI. The DETO₂X-AMI trial is designed to shed light on this important issue and give guidance to future recommendations.

• Acute Coronary Syndrome
• Non-ST Elevation (NSTEMI) Myocardial Infarction
• Acute ST Segment Elevation Myocardial Infarction
• Angina, Unstable

• No Intervention: No oxygen

  For patients randomised to withholding oxygen treatment

  • no oxygen is administered at any time as long as the oxygen saturation is ≥90% on pulse oximeter (repetitive checks are performed)
  • all patients receive standard acute coronary syndrome treatment including reperfusion strategies
  • observation duration 12 hours
• Active Comparator: Oxygen

  For patients randomised to oxygen therapy:

  • 6 L/min of oxygen delivered by oxymask® started immediately after inclusion of the ambulance service or in the emergency department given continuously for 6-12 hours (at least 6 hours)
  • all patients receive standard acute coronary syndrome treatment including reperfusion strategies
  Intervention: Drug: Oxygen

• Rawles JM, Kenmure AC. Controlled trial of oxygen in uncomplicated myocardial infarction. Br Med J. 1976 May 8;1(6018):1121-3.
• Farquhar H, Weatherall M, Wijesinghe M, Perrin K, Ranchord A, Simmonds M, Beasley R. Systematic review of studies of the effect of hyperoxia on coronary blood flow. Am Heart J. 2009 Sep;158(3):371-7. Epub 2009 Jul 15. Review.
• Ranchord AM, Argyle R, Beynon R, Perrin K, Sharma V, Weatherall M, Simmonds M, Heatlie G, Brooks N, Beasley R. High-concentration versus titrated oxygen therapy in ST-elevation myocardial infarction: a pilot randomized controlled trial. Am Heart J. 2012 Feb;163(2):168-75. doi: 10.1016/j.ahj.2011.10.013. Epub 2012 Jan 13.
• Ukholkina GB, Kostianov IIu, Kuchkina NV, Grendo EP, Gofman IaB. [Effect of oxygenotherapy used in combination with reperfusion in patients with acute myocardial infarction]. Kardiologiia. 2005;45(5):59. Russian.
• Moradkhan R, Sinoway LI. Revisiting the role of oxygen therapy in cardiac patients. J Am Coll Cardiol. 2010 Sep 21;56(13):1013-6. doi: 10.1016/j.jacc.2010.04.052.
• Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev. 2010 Jun 16;(6):CD007160. doi: 10.1002/14651858.CD007160.pub2. Review.
• Burls A, Cabello JB, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction: a systematic review and meta-analysis. Emerg Med J. 2011 Feb 23; [Epub ahead of print]
• Fröbert O, Lagerqvist B, Gudnason T, Thuesen L, Svensson R, Olivecrona GK, James SK. Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE trial). A multicenter, prospective, randomized, controlled clinical registry trial based on the Swedish angiography and angioplasty registry (SCAAR) platform. Study design and rationale. Am Heart J. 2010 Dec;160(6):1042-8.
• Kones R. Oxygen therapy for acute myocardial infarction-then and now. A century of uncertainty. Am J Med. 2011 Nov;124(11):1000-5. doi: 10.1016/j.amjmed.2011.04.034. Review.
• Shuvy M, Atar D, Gabriel Steg P, Halvorsen S, Jolly S, Yusuf S, Lotan C. Oxygen therapy in acute coronary syndrome: are the benefits worth the risk? Eur Heart J. 2013 Jun;34(22):1630-5. doi: 10.1093/eurheartj/eht110. Epub 2013 Apr 3.
• Stub D, Smith K, Bernard S, Bray JE, Stephenson M, Cameron P, Meredith I, Kaye DM; AVOID Study. A randomized controlled trial of oxygen therapy in acute myocardial infarction Air Verses Oxygen In myocarDial infarction study (AVOID Study). Am Heart J. 2012 Mar;163(3):339-345.e1.

Inclusion Criteria:

• symptoms (chest pain, dyspnea) indicating acute myocardial ischemia within the last 6 hours
• ECG changes (ST-segment elevation ≥ 2 mm V1-V4, or ≥ 1 mm in other leads, ST-segment depression >1 mm in any lead, negative T-wave in leads V2-V6, pathological Q-wave in at least 2 adjacent leads), left bundle branch block

and/or elevated levels of cardiac troponin levels in the ED

indicating acute myocardial ischemia

• oxygen saturation ≥90% (pulse oximeter)
• age ≥30

Exclusion Criteria:

• unwillingness to participate
• inability to comprehend given information
• continuous oxygen delivery at home prior to inclusion
• cardiac arrest prior to inclusion

• Swedish Heart Lung Foundation
• Swedish Foundation for Strategic Research