Overview

This trial is active, not recruiting.

Conditions acute myocardial infarction (ami), acute coronary syndrome (acs), st elevation (stemi) myocardial infarction, ischemic reperfusion injury, non-st elevation (nstemi) myocardial infarction, angina, unstable
Treatment oxygen
Phase phase 3
Sponsor Karolinska Institutet
Collaborator University Hospital, Linkoeping
Start date October 2014
End date December 2015
Trial size 175 participants
Trial identifier NCT02290080, DETO2X-biomarkers 2012/287-12

Summary

Oxygen treatment is widely used in acutely ill patients, both pre-hospital and in hospital. The indication for oxygen is sometimes unquestionable, such as in many hypoxic patients, but in other situations its use is more of a practise and much less based on scientific evidence. In particular, oxygen treatment is routinely used in patients with a suspected heart attack and variably recommended in guidelines, despite very limited data supporting a beneficial effect. Indeed, a few studies even indicate that oxygen treatment might be harmful.

Immediate re-opening of the acutely blocked artery to the heart muscle is the treatment of choice to limit permanent injury. However, the sudden re-initiation of blood flow achieved with primary percutaneous coronary intervention (PCI), the reopening and stenting of the blocked vessel, can give rise to further endothelial and myocardial damage, so-called reperfusion injury. Ischemia and reperfusion associated myocardial injury (IR-injury) involves a wide range of pathological processes. Vascular leakage, activation of cell death programs, thrombocytes and white blood cells leading to extended inflammation and formation of clots are examples of those effects.

The role of oxygen treatment on these pathological processes, on the extent of IR-injury and the final infarct size in patients with acute myocardial infarctions (AMI) has not previously been studied.

In an ongoing national multicentre, randomized, registry based clinical trial, the DETO2X-AMI trial (NCT01787110), the effect of oxygen on morbidity and mortality in ACS patients is being investigated.

The present DETO2X-biomarkers study is a substudy of the DETO2X-AMI trial, evaluating the effect of oxygen treatment on biological systems involved in the pathogenesis of reversible and irreversible myocardial damage and cell death in ACS.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking single blind (outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
For patients randomized 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
oxygen
see arm description
(No Intervention)
For patients randomized 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

Primary Outcomes

Measure
Plasma concentration levels over time of biomarkers of oxidative stress, apoptosis, inflammation and platelet aggregation
time frame: Within 8hours from baseline

Eligibility Criteria

Male or female participants at least 30 years old.

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 emergency department 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

Additional Information

Official title Determination of the Role of Oxygen on Mechanisms Involved in Ischemia-reperfusion Injury in Suspected Acute Myocardial Infarction by Biomarkers. A Sub Study to the DETO2X-AMI Trial.
Principal investigator Lennart Lennart, MD, PHD
Description The DETermination of the role of OXygen i suspected Acute Myocardial Infarction (DETO2X-AMI) trial (NCT01787110), an ongoing multicentre, randomized, registry based clinical trial, is investigating the effect of oxygen on morbidity and mortality in ACS patients. The present DETO2X-biomarkers study is a substudy of the DETO2X-AMI trial, evaluating the effect of oxygen treatment on biological systems involved in the pathogenesis of reversible and irreversible myocardial damage and cell death in ACS. AIMS To evaluate the effect of oxygen treatment on markers of oxidative stress in ACS patients. To assess the effect of oxygen treatment on soluble markers of apoptosis, MMPs and TIMPs in ACS patients. To study the effect of oxygen treatment on systemic inflammatory activity and leukocyte activation. To evaluate the effect of oxygen treatment on platelet activation in ACS patients. HYPOTHESIS The main hypothesis is that 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 worsening the prognosis. STUDY DESIGN and POPULATION The present study is a biomarker substudy of the DETO2X-AMI trial. The design and population of the DETO2X-AMI trial has previously been described in detail (NCT01787110). All patients included in the DETO2X-AMI trial at Södersjukhuset Stockholm and University Hospital Linköping during the study period specified below are also eligible to be included in the DETO2X-biomarkers study. We intend to include 150 patients with suspected AMI. STUDY PLAN All study participants in the DETO2X-biomarkers study have been allocated to receive oxygen (6L/min) or no oxygen treatment as part of the DETO2X-AMI trial. To a variable degree, the participants have already started this treatment when entering the biomarker substudy. Baseline blood samples will be collected as soon as possible after inclusion in the DETO2X-AMI trial, preferably prior to initiation of oxygen treatment. Study subjects will then continue to receive their allocated DETO2X-AMI study treatment. A second set of blood samples will be collected 5-7 hours after randomisation in the DETO2X-AMI trial, and always prior to discontinuation of oxygen treatment. ANALYSIS of blood samples As a marker of oxidative stress, plasma-isoprostane will be measured using gas chromatography combined with a massspectrometric detector. Soluble markers of apoptosis, MMP-2 and TIMP-2 will be analyzed by Luminex. Plasma inflammatory markers (C-reactive protein (CRP) and interleukin (IL)-6), myeloperoxidase, and markers of platelet activation will be analysed by ELISA. Flow cytometry will be used to analyse neutrophil integrin receptors and platelet-leukocyte aggregates in whole blood. Whole blood will be fixated and red blood cells lysed before analysis. EFFICACY OUTCOME To determine the effect of oxygen treatment on biomarkers of oxidative stress, apoptosis, matrix metalloproteinases, markers of inflammation, and leukocyte and platelet activation in patients admitted to hospital due to suspected AMI. SUMMARY The DETO2X-AMI trial will address the effects of oxygen on morbidity and mortality in ACS patients. The present DETO2X-biomarkers substudy is evaluating effects of oxygen treatment on biological systems involved in the pathogenesis of reversible and irreversible myocardial damage and cell death in ACS and may add essential new knowledge to the mechanistics of ischaemic myocardial injury.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Karolinska Institutet.