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.
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Karolinska Institutet
- Enrollment
- 175
- Locations
- 2
- Primary Endpoint
- Plasma concentration levels over time of biomarkers of oxidative stress, apoptosis, inflammation and platelet aggregation
Study Overview
Brief 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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 30 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Exclusion Criteria
- •unwillingness to participate
- •inability to comprehend given information
- •continuous oxygen delivery at home prior to inclusion
- •cardiac arrest prior to inclusion
Arms & Interventions
Oxygen
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
Intervention: Oxygen (Drug)
Outcomes
Primary Outcomes
Plasma concentration levels over time of biomarkers of oxidative stress, apoptosis, inflammation and platelet aggregation
Time Frame: Within 8hours from baseline
Venous blood samples will be collected at baseline and 5-7 hours after baseline. Plasma concentration levels will be analyzed for Interleukin (IL)-6 \[pg/mL\], CRP \[mg/L\], Isoprostane \[pg/mL\], Soluble TNF receptor 1 \[pg/mL\], Soluble TNF receptor 2 \[pg/mL\], Soluble Fas \[pg/mL\], Soluble Fas ligand (pg/mL\], MMP-2 \[ng/mL\], TIMP-2 \[ng/mL\], Soluble P-selectin \[ng/mL\], Platelet factor (PF)-4 \[ng/mL\], Beta-thromboglobulin \[ng/mL\]. Optional, flow cytometry will be used to analyse neutrophil integrin receptors (CD11b/CD18) and platelet-leukocyte aggregates (CD41a/CD11b/CD45) in whole blood. Whole blood will be fixated and red blood cells lysed before analysis.
Secondary Outcomes
No secondary outcomes reported
Investigators
Leif Svensson
MD, PHD
Karolinska Institutet