Ignite Creation Date:
2024-05-06 @ 3:27 AM
Last Modification Date:
2024-10-26 @ 11:33 AM
Study NCT ID:
NCT02290080
Status:
COMPLETED
Last Update Posted:
2017-12-11
First Post:
2014-11-08
Brief Title:
Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction by Biomarkers
Sponsor:
Karolinska Institutet
Organization:
Karolinska Institutet
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2017-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DETO2X-bio
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
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
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 6Lmin 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
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 6Lmin 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None