An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction

Acute Coronary Syndrome Clinical Trial

— DETO2X-AMI  

Official title:

DETermination of the Role of OXygen in Suspected Acute Myocardial Infarction (DETO2X-AMI) Based on the SWEDEHEART Registry

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01787110
• Other study ID #: DETO2X-AMI 2012/287-12
• Status: Completed
• Phase: Phase 3
• First received: February 1, 2013
• Last updated: December 8, 2017
• Start date: April 2013
• Est. completion date: December 30, 2016

Study information

• Verified date: March 2017
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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 in patients below 75 years of age).

All follow-up will be carried out in SWEDEHEART and other national registries such as the national cause of death register (dödsorsaksregister) or the national patient register (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.

EFFICACY OUTCOMES:

Primary efficacy outcome

All-cause mortality at one year in all patients with suspected AMI (ITT).

Secondary efficacy outcomes

In the ITT population and AMI cohort:

• MACE 1: composite of all-cause mortality or rehospitalization with heart failure*

• MACE 2: composite of all-cause mortality or rehospitalization with heart failure or readmission with myocardial infarction

• rehospitalization with heart failure

• rehospitalization with AMI

• rehospitalization with shock (Kilip ≥3)*

• cardiovascular death *

• health economy

In the STEMI cohort: MACE as a composite of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis* plus as above.

*These outcomes were specified after the trial had started, but before any treatment comparisons were available.

Primary and secondary outcomes will be assessed at 30 days and one year of follow up. Supplementary per-protocol analysis will be performed.

Subgroup analyses consist of predefined subgroups including gender, age, AMI/Non-AMI, Type-I AMI ( STEMI/NSTEMI), smokers, Hb, oxygen saturation levels, patients with chronic obstructive pulmonary disease, chronic kidney disease and diabetes mellitus.

Two main sub studies will be performed:

DETO2X-Biomarkers, a multicenter sub study to the DETO2X-AMI trial assessing if oxygen treatment enhances oxidative stress, systemic inflammation, and markers of apoptosis and MMPs in ACS patients, thereby potentially increasing myocardial damage and cell death, and potentially the prognosis (see separate trial protocol or clinicaltrials.gov NCT02290080 for details).

DETO2X-OXYPAIN 2, a multicenter sub study to the DETO2X-AMI trial at centers with catheter laboratories evaluating a possible analgesic effect of oxygen in using visual-analog scale (VAS).

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 cause of death register 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6629
• Est. completion date: December 30, 2016
• Est. primary completion date: December 30, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Oxygen
see arm description

Locations

Country	Name	City	State
Sweden	Enköping Hospital	Enköping
Sweden	Gävle Hospital	Gävle
Sweden	Gothenburg University Hospital, Östra	Gothenburg
Sweden	Gothenburg University Hospital, Sahlgrenska	Gothenburg
Sweden	Hallands Hospital Halmstad	Halmstad
Sweden	Ryhov Hospital Jönköping	Jönköping
Sweden	Kalmar Regional Hospital	Kalmar
Sweden	Karlstad Hospital	Karlstad
Sweden	Kiruna Hospital	Kiruna
Sweden	Köping Hospital	Köping
Sweden	Kristianstad Hospital	Kristianstad
Sweden	Skaraborgs Hospital Lidköping	Lidköping
Sweden	Linköping University Hospital	Linköping
Sweden	Skåne University Hospital Lund	Lund
Sweden	Skåne University Hospital Malmö	Malmö
Sweden	Sahlgrenska Universitetssjukhus Mölndal	Mölndal
Sweden	Vrinnevi Hospital Norrköping	Norrköping
Sweden	Norrtälje Hospital	Norrtälje
Sweden	Nyköping Hospital	Nyköping
Sweden	Örebro University Hospital	Örebro
Sweden	Örnsköldsvik Hospital	Örnsköldsvik
Sweden	Östersund Hospital	Östersund
Sweden	Skaraborgs Hospital Skövde	Skövde
Sweden	Danderyds Sjukhus	Stockholm
Sweden	Karolinska University Hospital Huddinge	Stockholm
Sweden	Karolinska University Hospital Solna	Stockholm
Sweden	Södersjukhuset	Stockholm
Sweden	St: Göran Hospital	Stockholm
Sweden	Härnosand Hospital Sundsvall	Sundsvall
Sweden	Trelleborg Hospital	Trelleborg
Sweden	Norrlands University Hospital	Umeå
Sweden	Uppsala University Hospital	Uppsala
Sweden	Hallands Hospital Varberg	Varberg
Sweden	Växjö Hospital	Växjö

Sponsors (4)

Lead Sponsor	Collaborator
Karolinska Institutet	Swedish Foundation for Strategic Research, Swedish Heart Lung Foundation, The Swedish Research Council

Country where clinical trial is conducted

Sweden, 

References & Publications (20)

Bulluck H, Hausenloy DJ. Letter by Bulluck and Hausenloy Regarding Article, "Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction". Circulation. 2016 Jan 19;133(3):e28. doi: 10.1161/CIRCULATIONAHA.115.017968. — View Citation

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 Nov;28(11):917-23. doi: 10.1136/emj.2010.103564. Epub 2011 Feb 23. Review. — View Citation

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. Update in: Cochrane Database Syst Rev. 2013;8:CD007160. — View Citation

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. doi: 10.1016/j.ahj.2009.05.037. Epub 2009 Jul 15. Review. — View Citation

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. doi: 10.1016/j.ahj.2010.08.040. — View Citation

Fröbert O, Lagerqvist B, Olivecrona GK, Omerovic E, Gudnason T, Maeng M, Aasa M, Angerås O, Calais F, Danielewicz M, Erlinge D, Hellsten L, Jensen U, Johansson AC, Kåregren A, Nilsson J, Robertson L, Sandhall L, Sjögren I, Ostlund O, Harnek J, James SK; TASTE Trial. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med. 2013 Oct 24;369(17):1587-97. doi: 10.1056/NEJMoa1308789. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Aug 21;371(8):786. — View Citation

Hofmann R, James SK, Svensson L, Witt N, Frick M, Lindahl B, Östlund O, Ekelund U, Erlinge D, Herlitz J, Jernberg T. DETermination of the role of OXygen in suspected Acute Myocardial Infarction trial. Am Heart J. 2014 Mar;167(3):322-8. doi: 10.1016/j.ahj.2013.09.022. Epub 2013 Dec 19. — View Citation

James S, Rao SV, Granger CB. Registry-based randomized clinical trials--a new clinical trial paradigm. Nat Rev Cardiol. 2015 May;12(5):312-6. doi: 10.1038/nrcardio.2015.33. Epub 2015 Mar 17. Review. — View Citation

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. — View Citation

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. — View Citation

Nedeljkovic ZS, Jacobs AK. Oxygen for ST-Segment-Elevation Myocardial Infarction: Still Up in the Air. Circulation. 2015 Jun 16;131(24):2101-3. doi: 10.1161/CIRCULATIONAHA.115.017072. Epub 2015 May 22. — View Citation

Nehme Z, Stub D, Bernard S, Stephenson M, Bray JE, Cameron P, Meredith IT, Barger B, Ellims AH, Taylor AJ, Kaye DM, Smith K; AVOID Investigators. Effect of supplemental oxygen exposure on myocardial injury in ST-elevation myocardial infarction. Heart. 2016 Mar;102(6):444-51. doi: 10.1136/heartjnl-2015-308636. Epub 2016 Jan 6. — View Citation

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. — View Citation

Rawles JM, Kenmure AC. Controlled trial of oxygen in uncomplicated myocardial infarction. Br Med J. 1976 May 8;1(6018):1121-3. — View Citation

Sepehrvand N, Ezekowitz JA. Oxygen Therapy in Patients With Acute Heart Failure: Friend or Foe? JACC Heart Fail. 2016 Oct;4(10):783-790. doi: 10.1016/j.jchf.2016.03.026. Epub 2016 Jun 8. Review. — View Citation

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. Review. — View Citation

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. doi: 10.1016/j.ahj.2011.11.011. — View Citation

Stub D, Smith K, Bernard S, Nehme Z, Stephenson M, Bray JE, Cameron P, Barger B, Ellims AH, Taylor AJ, Meredith IT, Kaye DM. Response to Letter Regarding Article, "Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction". Circulation. 2016 Jan 19;133(3):e29. doi: 10.1161/CIRCULATIONAHA.115.019038. — View Citation

Stub D, Smith K, Bernard S, Nehme Z, Stephenson M, Bray JE, Cameron P, Barger B, Ellims AH, Taylor AJ, Meredith IT, Kaye DM; AVOID Investigators. Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation. 2015 Jun 16;131(24):2143-50. doi: 10.1161/CIRCULATIONAHA.114.014494. Epub 2015 May 22. — View Citation

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. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year all-cause mortality	1-year all-cause mortality on an intention to treat basis (ITT)	1 year
Secondary	MACE 1	All-cause mortality or rehospitalization with heart failure at 1-year	1 year
Secondary	MACE 2	All-cause mortality or rehospitalization with heart failure or readmission with myocardial infarction at 1-year	1 year
Secondary	STEMI-PCI-MACE	All-cause death or rehospitalization with MI or cardiogenic shock or stent thrombosis at one year	1 year
Secondary	Rehospitalization with heart failure	Rehospitalization with heart failure at 1-year	1 year
Secondary	Rehospitalization with AMI	Rehospitalization with AMI at 1-year	1 year
Secondary	Rehospitalization with shock (Killip =3)	Rehospitalization with shock (Killip =3) at 1-year	1 year
Secondary	Cardiovascular death	Cardiovascular death at 1-year	1 year
Secondary	Health economics	Health economics concerning supplemental oxygen treatment from prehospital contact of the emergency service, hospital stay until follow-up 1 year in patients with AMI below 75 years of age	1 year

External Links

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