Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction by Biomarkers

NCT02290080 | Completed Phase 3

• 1 other identifier: DETO2X-biomarkers 2012/287-12
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 2

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.

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

Keywords

acute myocardial infarction (AMI); acute coronary syndrome (ACS); ST-segment elevation myocardial infarction (STEMI); Non ST-segment elevation myocardial infarction (NSTEMI); Ischemic Reperfusion injury (IR-injury); Biomarkers; Oxygen; Apoptosis; Fluorescence-activated cell sorting (FACS); Flow cytometry; Matrix metalloproteinase (MMP)

Outcome Measures

Primary Outcomes (1)

• Plasma concentration levels over time of biomarkers of oxidative stress, apoptosis, inflammation and platelet aggregation

  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.

  Within 8hours from baseline

Study Arms (2)

Oxygen

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

Drug: Oxygen

No oxygen

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

Interventions

Oxygen DRUG

see arm description

Oxygen

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• unwillingness to participate
• inability to comprehend given information

Sponsors & Collaborators

• Karolinska Institutet: lead
• University Hospital, Linkoeping: collaborator

Study Sites (2)

Linköping University Hospital

Linköping, 58191, Sweden

Location

Södersjukhuset

Stockholm, 11883, Sweden

Location

Related Publications (9)

• Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev. 2013 Aug 21;(8):CD007160. doi: 10.1002/14651858.CD007160.pub3.

  PMID: 23963794 BACKGROUND

• Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121-35. doi: 10.1056/NEJMra071667. No abstract available.

  PMID: 17855673 BACKGROUND

• Ekstrom M, Eriksson P, Tornvall P. Vaccination, a human model of inflammation, activates systemic inflammation but does not trigger proinflammatory gene expression in adipose tissue. J Intern Med. 2008 Dec;264(6):613-7. doi: 10.1111/j.1365-2796.2008.01998.x. No abstract available.

  PMID: 19017180 BACKGROUND

• Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011 Nov 7;17(11):1391-401. doi: 10.1038/nm.2507.

  PMID: 22064429 BACKGROUND

• 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.

  PMID: 23554440 BACKGROUND

• Piper HM, Meuter K, Schafer C. Cellular mechanisms of ischemia-reperfusion injury. Ann Thorac Surg. 2003 Feb;75(2):S644-8. doi: 10.1016/s0003-4975(02)04686-6.

  PMID: 12607706 BACKGROUND

• Hofmann R, James SK, Svensson L, Witt N, Frick M, Lindahl B, Ostlund 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.

  PMID: 24576515 RESULT

• Andell P, James S, Ostlund O, Yndigegn T, Sparv D, Pernow J, Jernberg T, Lindahl B, Herlitz J, Erlinge D, Hofmann R. Oxygen therapy in suspected acute myocardial infarction and concurrent normoxemic chronic obstructive pulmonary disease: a prespecified subgroup analysis from the DETO2X-AMI trial. Eur Heart J Acute Cardiovasc Care. 2020 Dec;9(8):984-992. doi: 10.1177/2048872619848978. Epub 2019 May 13.

  PMID: 31081342 DERIVED

• Hofmann R, Tornvall P, Witt N, Alfredsson J, Svensson L, Jonasson L, Nilsson L. Supplemental oxygen therapy does not affect the systemic inflammatory response to acute myocardial infarction. J Intern Med. 2018 Apr;283(4):334-345. doi: 10.1111/joim.12716. Epub 2017 Dec 11.

  PMID: 29226465 DERIVED

Related Links

• Homepage of the DETO2X trial

MeSH Terms

Conditions

Acute Coronary Syndrome; ST Elevation Myocardial Infarction; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Angina, Unstable

Interventions

Oxygen

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases

Study Officials

• Lennart Lennart, MD, PHD

  Department of Medical and Health Sciences, Linköping University, and Department of Cardiology, University Hospital, 58185 Linköping, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PHD

Study Record Dates

• First Submitted: November 8, 2014
• First Posted: November 13, 2014
• Study Start: October 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 11, 2017

Record last verified: 2017-12

Locations

SE (2)