Clinical trial NCT01787110: An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction
Official title: DETermination of the Role of OXygen in Suspected Acute Myocardial Infarction (DETO2X-AMI) Based on the SWEDEHEART Registry
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Coronary Syndrome
Non-ST Elevation (NSTEMI) Myocardial Infarction
Acute ST Segment Elevation Myocardial Infarction
Angina, Unstable
Keywords: Acute coronary syndrome
Acute myocardial infarction
Non ST-segment Myocardial Infarction
ST-segment Myocardial Infarction
STEMI
NSTEMI
Oxygen
Unstable angina
Randomised trial
CMR
Mortality
RCRT
RRCT
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Swedish Heart Lung Foundation
name: Swedish Foundation for Strategic Research
name: The Swedish Research Council
First posted: 2013-02-08
Enrollment: 6629
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 1-year all-cause mortality
timeFrame: 1 year
Secondary outcomes:
measure: MACE 1
timeFrame: 1 year
measure: MACE 2
timeFrame: 1 year
measure: STEMI-PCI-MACE
timeFrame: 1 year
measure: Rehospitalization with heart failure
timeFrame: 1 year
measure: Rehospitalization with AMI
timeFrame: 1 year
measure: Rehospitalization with shock (Killip ≥3)
timeFrame: 1 year
measure: Cardiovascular death
timeFrame: 1 year
measure: Health economics
timeFrame: 1 year
Other outcomes:
Locations:
city: Enköping
country: Sweden
facility: Enköping Hospital
city: Gothenburg
country: Sweden
facility: Gothenburg University Hospital, Sahlgrenska
city: Gothenburg
country: Sweden
facility: Gothenburg University Hospital, Östra
city: Gävle
country: Sweden
facility: Gävle Hospital
city: Halmstad
country: Sweden
facility: Hallands Hospital Halmstad
city: Jönköping
country: Sweden
facility: Ryhov Hospital Jönköping
city: Kalmar
country: Sweden
facility: Kalmar Regional Hospital
city: Karlstad
country: Sweden
facility: Karlstad Hospital
city: Kiruna
country: Sweden
facility: Kiruna Hospital
city: Kristianstad
country: Sweden
facility: Kristianstad Hospital
city: Köping
country: Sweden
facility: Köping Hospital
city: Lidköping
country: Sweden
facility: Skaraborgs Hospital Lidköping
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital Lund
city: Malmö
country: Sweden
facility: Skåne University Hospital Malmö
city: Mölndal
country: Sweden
facility: Sahlgrenska Universitetssjukhus Mölndal
city: Norrköping
country: Sweden
facility: Vrinnevi Hospital Norrköping
city: Norrtälje
country: Sweden
facility: Norrtälje Hospital
city: Nyköping
country: Sweden
facility: Nyköping Hospital
city: Skövde
country: Sweden
facility: Skaraborgs Hospital Skövde
city: Stockholm
country: Sweden
facility: St: Göran Hospital
city: Stockholm
country: Sweden
facility: Södersjukhuset
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Solna
city: Stockholm
country: Sweden
facility: Danderyds Sjukhus
city: Sundsvall
country: Sweden
facility: Härnosand Hospital Sundsvall
city: Trelleborg
country: Sweden
facility: Trelleborg Hospital
city: Umeå
country: Sweden
facility: Norrlands University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Varberg
country: Sweden
facility: Hallands Hospital Varberg
city: Växjö
country: Sweden
facility: Växjö Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
city: Örnsköldsvik
country: Sweden
facility: Örnsköldsvik Hospital
city: Östersund
country: Sweden
facility: Östersund Hospital
Study officials:
affiliation: Karolinska Institutet
name: Leif Svensson, MD, PHD
role: STUDY_DIRECTOR
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