Myocardial InfarctionPhase 1NCT02286544
Effects of Oxygen Treatment on Mechanisms Involved in Ischemia-reperfusion Injury: A Pilot Study in Healthy Volunteers
A Phase 1 study testing Salmonella typhi vaccine (Typhim Vi®), Oxygen (Oxymask®) and Atorvastatin in people with Myocardial Infarction and Inflammation, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
Oxygen treatment is widely used in acutely ill patients. In particular, oxygen treatment is routinely used in acute coronary syndrome (ACS) patients with suspected acute myocardial infarction and variably recommended in ACS-guidelines, despite very limited data supporting a beneficial effect. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Myocardial Infarction, Inflammation, Acute Coronary Syndrome (ACS)
- What is being tested?
- Salmonella typhi vaccine (Typhim Vi®), Oxygen (Oxymask®) and Atorvastatin
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteSweden
- Study dates
- Oct 2014to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-40 years
- Male gender
Who cannot join
- Female gender
- Not willing to participate
- Not able to communicate or to understand study instructions
- Participation in another on-going trial
- Any chronic disease
- Any acute disease within 30 days of study inclusion
- Any regular or temporary medication within 15 days of study inclusion
- Current smokers
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Oxygen Treatment on Mechanisms Involved in Ischemia-reperfusion Injury: A Single Center, Randomized, Controlled Pilot Study in Healthy Volunteers
Oxygen treatment is widely used in acutely ill patients. In particular, oxygen treatment is routinely used in acute coronary syndrome (ACS) patients with suspected acute myocardial infarction and variably recommended in ACS-guidelines, despite very limited data supporting a beneficial effect.
Immediate re-opening of the acutely occluded infarct-related bloodvessel via primary percutaneous coronary intervention (PCI) is the treatment of choice to limit ischemic injury in the setting of ST-elevation ACS (STE-ACS). However, the sudden re-initiation of blood flow achieved with primary PCI can give rise to further 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, transcriptional reprogramming, no reflow phenomenon and innate and adaptive immune activation all contribute to tissue damage, thereby determining the infarct size. The effect of oxygen treatment on these pathological processes, on the extent of IR-injury and the final infarct size in STE-ACS patients has not previously been studied.
Read more
ACS is characterized by a systemic inflammation with typical elevations of soluble inflammatory markers as well as changes in white blood cells. The inflammatory reaction might be considered helpful in restoring myocardial tissue structure and function, but on the other hand it might worsen IR-injury by activating various pathological processes. In human experimental studies, Salmonella typhi vaccine has been used to create a standardized model of systemic inflammation and when administered to healthy volunteers the vaccination has not been associated with any adverse events.
In an ongoing register randomized multicentre clinical trial, the DETO2X (Determination of role of oxygen in suspected acute myocardial infarction) study, the effect of oxygen on morbidity and mortality in ACS patients is being investigated. In a substudy of the DETO2X-trial, the investigators have planned to evaluate the effect of oxygen treatment on IR-injury in STE-ACS as assessed by biomarkers reflecting various aspects of the pathological processes involved.
The presented study is an experimental pilot study performed in healthy volunteers with a Salmonella typhi vaccine-induced inflammation with the purpose of studying effects of oxygen treatment on biological systems involved in the pathogenesis of IR- injury.
Read the detailed description
HYPOTHESIS The main hypothesis is that oxygen treatment can increase oxidative stress, systemic inflammation, markers of apoptosis, matrix metalloproteinases (MMPs) and their tissue inhibitor (TIMPs) in individuals subjected to endotoxin-induced inflammation. The investigators also hypothesize that pretreatment with statins can prevent this oxygen effect.
AIMS
- To evaluate whether oxygen treatment can increase oxidative stress in healthy volunteers subjected to vaccine-induced inflammation.
- To assess the effect of oxygen treatment on plasma levels of soluble markers of apoptosis, MMPs and TIMPs in healthy volunteers with vaccine-induced inflammation.
- To study the effect of oxygen treatment on systemic inflammatory activity and leukocyte subset distribution in healthy volunteers with vaccine-induced inflammation.
- To evaluate the effect of oxygen treatment on platelet aggregation in healthy volunteers with vaccine-induced inflammation.
- To determine whether a potential oxygen effect on these cellular- and biomarkers can be prevented by pretreatment with Atorvastatin.
- To serve as a pilot study and basis for power calculations for a future planned study: "Effects of oxygen treatment on biomarkers of reperfusion damage and infarct size in ST-elevation myocardial infarction patients undergoing primary PCI".
DESIGN The present study is an experimental randomized pilot study in healthy volunteers.
STUDY POPULATION The investigators intend to include 36 healthy male volunteers. Females will not be included, due to the potential risk of hazardous effects of Salmonella typhi vaccine and Atorvastatin to a fetus in case of pregnancy.
STUDY DESIGN
At the time of inclusion all study participants will be randomised into one of three intervention groups:
Group 1) Salmonella typhi vaccine Group 2) Salmonella typhi vaccine + oxygen treatment Group 3) Salmonella typhi vaccine + oxygen treatment + Atorvastatin At 8.00 am on study day a peripheral venous catheter will be inserted. This catheter will be used to collect blood sample during the study day. In addition, peripheral oxygen saturation will be measured by pulse oximetry. After baseline venous blood samples have been collected, all study participants will receive 0.5 mL of the Salmonella typhi vaccine as an intramuscular injection (Typhim Vi®, Sanofi Pasteur MSD, injection solution 25 microgram/0.5 mL).
Half an hour after vaccination is administered, oxygen treatment will be initiated (in group 2 and 3) at 6 L/min via Oxymask® and continued for 6 hours. During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry. In group 3, a single dose of Atorvastatin 80 mg will be given immediately prior to start of oxygen. Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.
An experienced registered nurse and a resident or specialist in Cardiology and Internal Medicine will be present during the entire study day taking care of all study interventions, collecting blood samples and register data into the case report form (CRF) including potential adverse events.
EFFICACY OUTCOMES
- To determine the effect of oxygen treatment on biomarkers of oxidative stress, apoptosis, matrix metalloproteinases, markers of inflammation and platelet aggregation in healthy volunteers with Salmonella typhi vaccine-induced inflammation.
- To compare levels of these cellular- and biomarkers over time during an 8-hour study day.
SUMMARY The presented study is an experimental randomized pilot study performed in healthy volunteers with a Salmonella typhi vaccine-induced inflammation with the purpose of studying to date unknown effects of oxygen treatment on biological systems involved in the pathogenesis of IR- injury. As part of the DETO2X trial series, this study aims to contribute essential knowledge to clarifying the role of oxygen in treatment of acute myocardial infarction.
- Being tested
- Salmonella typhi vaccine (Typhim Vi®), Oxygen (Oxymask®), Atorvastatin
- Keywords
- Myocardial Infarction, Oxygen, Inflammation, Acute coronary syndrome (ACS), ST-segment elevation myocardial infarction (STEMI), Reperfusion injury (IR-injury), Biomarkers, Normoxemia, Salmonella typhi, Vaccine-induced inflammation, Soluble markers of apoptosis, Leukocyte subset distribution, Matrix metalloproteinase (MMP), Biological Markers
- Medical subject headings
- Myocardial Infarction, Inflammation, Acute Coronary Syndrome, Reperfusion Injury, ST Elevation Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Salmonella typhi vaccine (Typhim Vi®)Biological
A peripheral venous catheter will be inserted. This catheter will be used to collect blood sample during the study day. In addition, peripheral oxygen saturation will be measured by pulse oximetry. After baseline venous blood samples have been collected, all study participants will receive 0.5 mL of the Salmonella typhi vaccine as an intramuscular injection (Typhim Vi®, Sanofi Pasteur MSD, injection solution 25 microgram/0.5 mL) Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.
Oxygen (Oxymask®)Drug
As in arm 1. Half an hour after vaccination is administered, oxygen treatment will be initiated at 6 L/min via Oxymask® and continued for 6 hours. During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry.
Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.
AtorvastatinDrug
Also called Lipitor
As in arm 1. Half an hour after vaccination is administered, oxygen treatment will be initiated at 6 L/min via Oxymask® and continued for 6 hours. During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry. A single dose of Atorvastatin 80 mg will be given immediately prior to start of oxygen. Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.
| Study group | Role | What they receive |
|---|---|---|
| Salmonella typhi vaccine | Active comparator | 0.5 mL Salmonella typhi vaccine Receives: Biological: Salmonella typhi vaccine (Typhim Vi®) |
| Salmonella typhi vaccine + oxygen | Experimental | 0.5 mL Salmonella typhi vaccine + 6l/min oxygen Receives: Biological: Salmonella typhi vaccine (Typhim Vi®); Drug: Oxygen (Oxymask®) |
| S. typhi vaccine + oxygen + Atorvastatin | Experimental | 0.5 mL Salmonella typhi vaccine + 6l/min oxygen + 80mg Atorvastatin Receives: Biological: Salmonella typhi vaccine (Typhim Vi®); Drug: Oxygen (Oxymask®); Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentration levels over time of biomarkers of oxidative stress, apoptosis, inflammation and platelet aggregation
Venous blood samples will be collected at 3, 6 and 8 hours after baseline and plasmaconcentration 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].
Measured: Within 8hours from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Linkoeping
- Responsible party
- Principal investigator, Leif Svensson, Karolinska Institutet
- Investigators
- Lennart Nilsson, MD, PHD, Principal investigator, Department of Medical and Health Sciences, Linköping University, and Department of Cardiology, University Hospital, 58185 Linköping, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02286544
- Sponsor's protocol ID
- DNR-2014/252-31
- Other IDs
- 2014-002282-30, 2014
- Status last verified
- Dec 2017
- First submitted
- 27 Oct 2014
- Last updated
- 11 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 24576515Cabello 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.
PubMed 23963794Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121-35. doi: 10.1056/NEJMra071667. No abstract available.
PubMed 17855673Ekstrom 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.
PubMed 19017180Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011 Nov 7;17(11):1391-401. doi: 10.1038/nm.2507.
PubMed 22064429Shuvy 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.
PubMed 23554440Piper 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.
PubMed 12607706
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Oxygen Treatment on Mechanisms Involved in Ischemia-reperfusion Injury: A Single Center, Randomized, Controlled Pilot Study in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02286544
- Acronym / sponsor ID
- DNR-2014/252-31
- Keywords
- Myocardial Infarction, Oxygen, Inflammation, Acute coronary syndrome (ACS), ST-segment elevation myocardial infarction (STEMI), Reperfusion injury (IR-injury), Biomarkers, Normoxemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- University Hospital, Linkoeping
- Study start
- Oct 2014 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 10 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Oxygen treatment is widely used in acutely ill patients. In particular, oxygen treatment is routinely used in acute coronary syndrome (ACS) patients with suspected acute myocardial infarction and variably recommended in ACS-guidelines, despite very limited data supporting a beneficial effect.
Immediate re-opening of the acutely occluded infarct-related bloodvessel via primary percutaneous coronary intervention (PCI) is the treatment of choice to limit ischemic injury in the setting of ST-elevation ACS (STE-ACS). However, the sudden re-initiation of blood flow achieved with primary PCI can give rise to further 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, transcriptional reprogramming, no reflow phenomenon and innate and adaptive immune activation all contribute to tissue damage, thereby determining the infarct size. The effect of oxygen treatment on these pathological processes, on the extent of IR-injury and the final infarct size in STE-ACS patients has not previously been studied.
ACS is characterized by a systemic inflammation with typical elevations of soluble inflammatory markers as well as changes in white blood cells. The inflammatory reaction might be considered helpful in restoring myocardial tissue structure and function, but on the other hand it might worsen IR-injury by activating various pathological processes. In human experimental studies, Salmonella typhi vaccine has been used to create a standardized model of systemic inflammation and when administered to healthy volunteers the vaccination has not been associated with any adverse events.
In an ongoing register randomized multicentre clinical trial, the DETO2X (Determination of role of oxygen in suspected acute myocardial infarction) study, the effect of oxygen on morbidity and mortality in ACS patients is being investigated. In a substudy of the DETO2X-trial, the investigators have planned to evaluate the effect of oxygen treatment on IR-injury in STE-ACS as assessed by biomarkers reflecting various aspects of the pathological processes involved.
The presented study is an experimental pilot study performed in healthy volunteers with a Salmonella typhi vaccine-induced inflammation with the purpose of studying effects of oxygen treatment on biological systems involved in the pathogenesis of IR- injury.
Detailed description
HYPOTHESIS The main hypothesis is that oxygen treatment can increase oxidative stress, systemic inflammation, markers of apoptosis, matrix metalloproteinases (MMPs) and their tissue inhibitor (TIMPs) in individuals subjected to endotoxin-induced inflammation. The investigators also hypothesize that pretreatment with statins can prevent this oxygen effect.
AIMS
- To evaluate whether oxygen treatment can increase oxidative stress in healthy volunteers subjected to vaccine-induced inflammation.
- To assess the effect of oxygen treatment on plasma levels of soluble markers of apoptosis, MMPs and TIMPs in healthy volunteers with vaccine-induced inflammation.
- To study the effect of oxygen treatment on systemic inflammatory activity and leukocyte subset distribution in healthy volunteers with vaccine-induced inflammation.
- To evaluate the effect of oxygen treatment on platelet aggregation in healthy volunteers with vaccine-induced inflammation.
- To determine whether a potential oxygen effect on these cellular- and biomarkers can be prevented by pretreatment with Atorvastatin.
- To serve as a pilot study and basis for power calculations for a future planned study: "Effects of oxygen treatment on biomarkers of reperfusion damage and infarct size in ST-elevation myocardial infarction patients undergoing primary PCI".
DESIGN The present study is an experimental randomized pilot study in healthy volunteers.
STUDY POPULATION The investigators intend to include 36 healthy male volunteers. Females will not be included, due to the potential risk of hazardous effects of Salmonella typhi vaccine and Atorvastatin to a fetus in case of pregnancy.
STUDY DESIGN
At the time of inclusion all study participants will be randomised into one of three intervention groups:
Group 1) Salmonella typhi vaccine Group 2) Salmonella typhi vaccine + oxygen treatment Group 3) Salmonella typhi vaccine + oxygen treatment + Atorvastatin At 8.00 am on study day a peripheral venous catheter will be inserted. This catheter will be used to collect blood sample during the study day. In addition, peripheral oxygen saturation will be measured by pulse oximetry. After baseline venous blood samples have been collected, all study participants will receive 0.5 mL of the Salmonella typhi vaccine as an intramuscular injection (Typhim Vi®, Sanofi Pasteur MSD, injection solution 25 microgram/0.5 mL).
Half an hour after vaccination is administered, oxygen treatment will be initiated (in group 2 and 3) at 6 L/min via Oxymask® and continued for 6 hours. During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry. In group 3, a single dose of Atorvastatin 80 mg will be given immediately prior to start of oxygen. Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.
An experienced registered nurse and a resident or specialist in Cardiology and Internal Medicine will be present during the entire study day taking care of all study interventions, collecting blood samples and register data into the case report form (CRF) including potential adverse events.
EFFICACY OUTCOMES
- To determine the effect of oxygen treatment on biomarkers of oxidative stress, apoptosis, matrix metalloproteinases, markers of inflammation and platelet aggregation in healthy volunteers with Salmonella typhi vaccine-induced inflammation.
- To compare levels of these cellular- and biomarkers over time during an 8-hour study day.
SUMMARY The presented study is an experimental randomized pilot study performed in healthy volunteers with a Salmonella typhi vaccine-induced inflammation with the purpose of studying to date unknown effects of oxygen treatment on biological systems involved in the pathogenesis of IR- injury. As part of the DETO2X trial series, this study aims to contribute essential knowledge to clarifying the role of oxygen in treatment of acute myocardial infarction.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Salmonella typhi vaccine | Active comparator | Biological: Salmonella typhi vaccine (Typhim Vi®)0.5 mL Salmonella typhi vaccine |
| Salmonella typhi vaccine + oxygen | Experimental | Biological: Salmonella typhi vaccine (Typhim Vi®), Drug: Oxygen (Oxymask®)0.5 mL Salmonella typhi vaccine + 6l/min oxygen |
| S. typhi vaccine + oxygen + Atorvastatin | Experimental | Biological: Salmonella typhi vaccine (Typhim Vi®), Drug: Oxygen (Oxymask®), Drug: Atorvastatin0.5 mL Salmonella typhi vaccine + 6l/min oxygen + 80mg Atorvastatin |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Age 18-40 years
- Male gender
Key exclusion criteria (8 listed)
- Female gender
- Not willing to participate
- Not able to communicate or to understand study instructions
- Participation in another on-going trial
- Any chronic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Salmonella typhi vaccine (Typhim Vi®)A peripheral venous catheter will be inserted. This catheter will be used to collect blood sample during the study day. In addition, peripheral oxygen saturation will be measured by pulse oximetry. After baseline venous blood samples have been collected, all study participants will receive 0.5 mL of the Salmonella typhi vaccine as an intramuscular injection (Typhim Vi®, Sanofi Pasteur MSD, injection solution 25 microgram/0.5 mL) Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended. | Biological | S. typhi vaccine + oxygen + Atorvastatin, Salmonella typhi vaccine, Salmonella typhi vaccine + oxygen |
| Oxygen (Oxymask®)As in arm 1. Half an hour after vaccination is administered, oxygen treatment will be initiated at 6 L/min via Oxymask® and continued for 6 hours. During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry. Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended. | Drug | S. typhi vaccine + oxygen + Atorvastatin, Salmonella typhi vaccine + oxygen |
| AtorvastatinAlso: LipitorAs in arm 1. Half an hour after vaccination is administered, oxygen treatment will be initiated at 6 L/min via Oxymask® and continued for 6 hours. During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry. A single dose of Atorvastatin 80 mg will be given immediately prior to start of oxygen. Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended. | Drug | S. typhi vaccine + oxygen + Atorvastatin |
Primary outcome
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 3, 6 and 8 hours after baseline and plasmaconcentration 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].
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2017.
- Background: PubMed 24576515Hofmann 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.
- Background: PubMed 23963794Cabello 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.
- Background: PubMed 17855673Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121-35. doi: 10.1056/NEJMra071667. No abstract available.
- Background: PubMed 19017180Ekstrom 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.
- Background: PubMed 22064429Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011 Nov 7;17(11):1391-401. doi: 10.1038/nm.2507.
- Background: PubMed 23554440Shuvy 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.
- Background: PubMed 12607706Piper 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.
Related trials for Myocardial Infarction
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
Active, not recruitingObservational study
A Longitudinal Cohort Study to Evaluate Cardiovascular Risk Factors and Disease in Haiti
Hypertension, Diabetes
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
Enrolling by invitation
The DANE-HEART Trial - Computed Tomography Coronary Angiography for Primary Prevention
Coronary Atherosclerosis and Other Heart Disease, Cardiovascular Diseases
Not yet recruitingObservational study
Elicit Drugs in Myocardial Infarction
Young Patients With Acute Myocardial Infarction
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lennart Nilsson, MD, PHD principal investigator
Department of Medical and Health Sciences, Linköping University, and Department of Cardiology, University Hospital, 58185 Linköping, Sweden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Salmonella typhi vaccine (Typhim Vi®), Oxygen (Oxymask®) and Atorvastatin in people with Myocardial Infarction and Inflammation, run by Karolinska Institutet at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma concentration levels over time of biomarkers of oxidative stress, apoptosis, inflammation and platelet aggregation (time frame: Within 8hours from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02286544, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2017.