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

Phase 3
Completed
Conditions
Acute Coronary Syndrome
Non-ST Elevation (NSTEMI) Myocardial Infarction
Acute ST Segment Elevation Myocardial Infarction
Angina, Unstable
Interventions
Registration Number
NCT01787110
Lead Sponsor
Karolinska Institutet
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
6629
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
OxygenOxygenFor 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
Primary Outcome Measures
NameTimeMethod
1-year all-cause mortality1 year

1-year all-cause mortality on an intention to treat basis (ITT)

Secondary Outcome Measures
NameTimeMethod
Cardiovascular death1 year

Cardiovascular death at 1-year

Rehospitalization with AMI1 year

Rehospitalization with AMI at 1-year

MACE 11 year

All-cause mortality or rehospitalization with heart failure at 1-year

MACE 21 year

All-cause mortality or rehospitalization with heart failure or readmission with myocardial infarction at 1-year

STEMI-PCI-MACE1 year

All-cause death or rehospitalization with MI or cardiogenic shock or stent thrombosis at one year

Health economics1 year

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

Rehospitalization with heart failure1 year

Rehospitalization with heart failure at 1-year

Rehospitalization with shock (Killip ≥3)1 year

Rehospitalization with shock (Killip ≥3) at 1-year

Trial Locations

Locations (34)

Södersjukhuset

🇸🇪

Stockholm, Sweden

Örnsköldsvik Hospital

🇸🇪

Örnsköldsvik, Sweden

Kristianstad Hospital

🇸🇪

Kristianstad, Sweden

St: Göran Hospital

🇸🇪

Stockholm, Sweden

Karolinska University Hospital Huddinge

🇸🇪

Stockholm, Sweden

Trelleborg Hospital

🇸🇪

Trelleborg, Sweden

Växjö Hospital

🇸🇪

Växjö, Sweden

Örebro University Hospital

🇸🇪

Örebro, Sweden

Enköping Hospital

🇸🇪

Enköping, Sweden

Gothenburg University Hospital, Östra

🇸🇪

Gothenburg, Sweden

Gävle Hospital

🇸🇪

Gävle, Sweden

Linköping University Hospital

🇸🇪

Linköping, Sweden

Gothenburg University Hospital, Sahlgrenska

🇸🇪

Gothenburg, Sweden

Hallands Hospital Halmstad

🇸🇪

Halmstad, Sweden

Kalmar Regional Hospital

🇸🇪

Kalmar, Sweden

Kiruna Hospital

🇸🇪

Kiruna, Sweden

Ryhov Hospital Jönköping

🇸🇪

Jönköping, Sweden

Karlstad Hospital

🇸🇪

Karlstad, Sweden

Skåne University Hospital Lund

🇸🇪

Lund, Sweden

Skåne University Hospital Malmö

🇸🇪

Malmö, Sweden

Köping Hospital

🇸🇪

Köping, Sweden

Skaraborgs Hospital Lidköping

🇸🇪

Lidköping, Sweden

Sahlgrenska Universitetssjukhus Mölndal

🇸🇪

Mölndal, Sweden

Vrinnevi Hospital Norrköping

🇸🇪

Norrköping, Sweden

Norrtälje Hospital

🇸🇪

Norrtälje, Sweden

Nyköping Hospital

🇸🇪

Nyköping, Sweden

Skaraborgs Hospital Skövde

🇸🇪

Skövde, Sweden

Karolinska University Hospital Solna

🇸🇪

Stockholm, Sweden

Danderyds Sjukhus

🇸🇪

Stockholm, Sweden

Härnosand Hospital Sundsvall

🇸🇪

Sundsvall, Sweden

Uppsala University Hospital

🇸🇪

Uppsala, Sweden

Hallands Hospital Varberg

🇸🇪

Varberg, Sweden

Norrlands University Hospital

🇸🇪

Umeå, Sweden

Östersund Hospital

🇸🇪

Östersund, Sweden

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