Myocardial InfarctionPhase 1/2SINTAMINCT02753478
Safety and Feasibility of Intracoronary Hypothermia in Acute Myocardial Infarction
A Phase 1/2 study testing intracoronary infusion with saline on 22 and 4°C in people with Myocardial Infarction, run by Catharina Ziekenhuis Eindhoven at 1 site in Netherlands.
Trial summary
Hypothermia may reduce infarct size in patients with acute myocardial infarction if provided before reperfusion. Human studies using systemic cooling methods failed to show a reduction in infarction size. The use of selective intracoronary hypothermia may overcome the problems of systemic cooling. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Infarction
- What is being tested?
- intracoronary infusion with saline on 22 and 4°C
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- Jun 2016to Nov 2016
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will be eligible for this study when they are admitted for acute ST elevation myocardial infarction with a total ST-segment deviation of more than 5 mm and presenting within 6 hours after onset of complaints.
- Patients should have a TIMI 0, 1 or 2 flow in the infarction related artery.
Who cannot join
- Cardiogenic shock or pre-shock
- Poor clinical condition with concomitant inconvenience like repeated vomiting, severe chest pain or elsewise according to the judgment of the treating interventionalist.
- Patients with previous myocardial infarction in the culprit area of with previous bypass surgery
- Tortuous coronary arteries
- Complex or long-lasting primary PCI expected
- Inability to understand and give informed consent either in first instance on the table or in second instance on the coronary care unit.
Show all 10Show fewer
- Other known myocardial diseases, such as moderate or severe left ventricular hypertrophy or cardiomyopathy
- Pregnancy
- First degree AV-block, Mobitz I and Mobitz II block, trifascicular block, or total AV block, Left- and Right Bundle Branch Block
- Patients in whom no access to the coronary circulation can be obtained by the femoral artery or in whom femoral access was problematic Severe concomitant disease or conditions with a life expectancy of less than one year
Trial locations and contacts
1 site in 1 country.
About this study
Hypothermia may reduce infarct size in patients with acute myocardial infarction if provided before reperfusion. Human studies using systemic cooling methods failed to show a reduction in infarction size. The use of selective intracoronary hypothermia may overcome the problems of systemic cooling.
The hypothesis of this study is that in patients with acute myocardial infarction, the induction of intracoronary hypothermia is safe and feasible.
Read the detailed description
In acute myocardial infarction, infarct size is directly related to short and long-term mortality and development of chronic heart failure.Therefore, limiting infarct size is of great worth. Therapies to reduce ischemic injury, by primarily primary percutaneous coronary intervention seem to be exhausted. Consequently, there still remains a need for efforts to develop therapies that target reperfusion injury to obtain additional reduction of infarct size.
Therapeutic hypothermia (32 - 35°C) attenuates reperfusion injury and therefore reduces infarct size in a variety of animal models of acute myocardial infarction (AMI), if provided before reperfusion. In human studies this reduction has not been confirmed so far, probably due to the fact that systemic cooling is slow in reducing temperature and therefore target temperature was not reached in time in a substantial number of patients or not reached at all. Furthermore, systemic cooling has side effects such as severe shivering, volume overload and an enhanced adrenergic state. However, subgroups of patients in all randomized clinical trials with anterior myocardial infarction who reached target temperature before reperfusion did show a reduction in infarct size.
To make therapeutic hypothermia into a valuable treatment for AMI, the method of inducing hypothermia has therefore to be modified. This method should be clinical feasible and quick enough to provide myocardial hypothermia before reperfusion, without prolonging symptom-to-balloon times and without the adverse effects of systemic cooling.
In this study the investigators will evaluate the safety and feasibility of intracoronary hypothermia in 10 patients with acute myocardial infarction.
In study patients, routine primary percutaneous intervention will be commenced. Before reperfusion, saline on room temperature will be infused though the occlusion in the infarct related artery using an over the wire balloon catheter during 10 minutes. The balloon will be inflated to prevent reperfusion in that phase. After 10 minutes the balloon will be deflated allowing reperfusion and infusion with saline on 4°C will be continued for 10 minutes. After this, a coronary stent will be placed. Primary end points are safety and feasibility of this method.
- Conditions
- Myocardial Infarction
- Being tested
- intracoronary infusion with saline on 22 and 4°C
- Keywords
- hypothermia
- Medical subject headings
- Myocardial Infarction, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intracoronary infusion with saline on 22 and 4°COther
Routine primary percutaneous intervention will be commenced. Patient will be asked to participate in the study.
Before reperfusion, saline on room temperature will be infused though the occlusion in the infarct related artery using an over the wire balloon catheter during 10 minutes. The balloon will be inflated to prevent reperfusion in that phase. After 10 minutes the balloon will be deflated allowing reperfusion and infusion with saline on 4°C will be continued for 10 minutes. After this, a coronary stent will be placed.
| Study group | Role | What they receive |
|---|---|---|
| intracoronary hypothermia group | Experimental | Patients who will receive intracoronary hypothermia before and during percutaneous coronary intervention Receives: Other: intracoronary infusion with saline on 22 and 4°C |
What is being measured
The primary outcome is the main question the study is designed to answer.
arrhythmia or AV-block (1st, 2nd or 3rd degree)
- Is there a higher incidence of rhythm- or conductance disturbances compared with the routine PCI procedure for myocardial infarction or is any other unforeseen side effect observed.
Measured: 0 - 20 minutes
Prolonging of door-to-balloon tome measured in minutes
- Is the protocol easy to perform
- Is a quick temperature drop achieved (< 5min.) As mentioned earlier, one of the hypotheses for the failure to prove benefit of induced hypothermia in earlier trials, was the relatively long time to achieve the target temperature or the failure to achieve the target temperature at all. Therefore, in this study a quick temperature drop should be recorded in the temperature wire placed distal to the coronary occlusion. A quick temperature drop is defined as a significant drop in distal coronary temperature (<5 °C) within 5 minutes after start of the infusion.
- After reaching the targeted temperature, is it possible to obtain a stable coronary temperature during 20 minutes.
- How long is he Door-to-balloon time delayed
Measured: 30 - 60 minutes
Secondary outcomes (1)
Time to target temperature in seconds
Time to target temperature
Measured: 0 - 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2016 (estimated)
- Study startJun 2016
- Primary completionNov 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catharina Ziekenhuis Eindhoven
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luuk Otterspoor, Catharina Ziekenhuis Eindhoven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02753478
- Sponsor's protocol ID
- SINTAMI
- Acronym
- SINTAMI
- Status last verified
- Nov 2016
- First submitted
- 4 Apr 2016
- Last updated
- 22 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: by publishing the results in a peer reviewed journal
Publications
Tissier R, Ghaleh B, Cohen MV, Downey JM, Berdeaux A. Myocardial protection with mild hypothermia. Cardiovasc Res. 2012 May 1;94(2):217-25. doi: 10.1093/cvr/cvr315. Epub 2011 Nov 29.
PubMed 22131353Otterspoor LC, Van't Veer M, van Nunen LX, Wijnbergen I, Tonino PA, Pijls NH. Safety and feasibility of local myocardial hypothermia. Catheter Cardiovasc Interv. 2016 Apr;87(5):877-83. doi: 10.1002/ccd.26139. Epub 2015 Aug 13.
PubMed 26269225
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Feasibility of Intracoronary Hypothermia in Acute Myocardial Infarction
- ClinicalTrials.gov ID
- NCT02753478
- Acronym / sponsor ID
- SINTAMI / SINTAMI
- Conditions
- Myocardial Infarction
- Keywords
- hypothermia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Catharina Ziekenhuis EindhovenUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 28 Apr 2016 (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.
Hypothermia may reduce infarct size in patients with acute myocardial infarction if provided before reperfusion. Human studies using systemic cooling methods failed to show a reduction in infarction size. The use of selective intracoronary hypothermia may overcome the problems of systemic cooling.
The hypothesis of this study is that in patients with acute myocardial infarction, the induction of intracoronary hypothermia is safe and feasible.
Detailed description
In acute myocardial infarction, infarct size is directly related to short and long-term mortality and development of chronic heart failure.Therefore, limiting infarct size is of great worth. Therapies to reduce ischemic injury, by primarily primary percutaneous coronary intervention seem to be exhausted. Consequently, there still remains a need for efforts to develop therapies that target reperfusion injury to obtain additional reduction of infarct size.
Therapeutic hypothermia (32 - 35°C) attenuates reperfusion injury and therefore reduces infarct size in a variety of animal models of acute myocardial infarction (AMI), if provided before reperfusion. In human studies this reduction has not been confirmed so far, probably due to the fact that systemic cooling is slow in reducing temperature and therefore target temperature was not reached in time in a substantial number of patients or not reached at all. Furthermore, systemic cooling has side effects such as severe shivering, volume overload and an enhanced adrenergic state. However, subgroups of patients in all randomized clinical trials with anterior myocardial infarction who reached target temperature before reperfusion did show a reduction in infarct size.
To make therapeutic hypothermia into a valuable treatment for AMI, the method of inducing hypothermia has therefore to be modified. This method should be clinical feasible and quick enough to provide myocardial hypothermia before reperfusion, without prolonging symptom-to-balloon times and without the adverse effects of systemic cooling.
In this study the investigators will evaluate the safety and feasibility of intracoronary hypothermia in 10 patients with acute myocardial infarction.
In study patients, routine primary percutaneous intervention will be commenced. Before reperfusion, saline on room temperature will be infused though the occlusion in the infarct related artery using an over the wire balloon catheter during 10 minutes. The balloon will be inflated to prevent reperfusion in that phase. After 10 minutes the balloon will be deflated allowing reperfusion and infusion with saline on 4°C will be continued for 10 minutes. After this, a coronary stent will be placed. Primary end points are safety and feasibility of this method.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| intracoronary hypothermia group | Experimental | Other: intracoronary infusion with saline on 22 and 4°CPatients who will receive intracoronary hypothermia before and during percutaneous coronary intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients will be eligible for this study when they are admitted for acute ST elevation myocardial infarction with a total ST-segment deviation of more than 5 mm and presenting within 6 hours after onset of complaints.
- Patients should have a TIMI 0, 1 or 2 flow in the infarction related artery.
Key exclusion criteria (10 listed)
- Cardiogenic shock or pre-shock
- Poor clinical condition with concomitant inconvenience like repeated vomiting, severe chest pain or elsewise according to the judgment of the treating interventionalist.
- Patients with previous myocardial infarction in the culprit area of with previous bypass surgery
- Tortuous coronary arteries
- Complex or long-lasting primary PCI expected
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 |
|---|---|---|
| intracoronary infusion with saline on 22 and 4°CRoutine primary percutaneous intervention will be commenced. Patient will be asked to participate in the study. Before reperfusion, saline on room temperature will be infused though the occlusion in the infarct related artery using an over the wire balloon catheter during 10 minutes. The balloon will be inflated to prevent reperfusion in that phase. After 10 minutes the balloon will be deflated allowing reperfusion and infusion with saline on 4°C will be continued for 10 minutes. After this, a coronary stent will be placed. | Other | intracoronary hypothermia group |
Primary outcome
arrhythmia or AV-block (1st, 2nd or 3rd degree)
Time frame: 0 - 20 minutes
- Is there a higher incidence of rhythm- or conductance disturbances compared with the routine PCI procedure for myocardial infarction or is any other unforeseen side effect observed.
Prolonging of door-to-balloon tome measured in minutes
Time frame: 30 - 60 minutes
* Is the protocol easy to perform * Is a quick temperature drop achieved (< 5min.) As mentioned earlier, one of the hypotheses for the failure to prove benefit of induced hypothermia in earlier trials, was the relatively long time to achieve the target temperature or the failure to achieve the target temperature at all. Therefore, in this study a quick temperature drop should be recorded in the temperature wire placed distal to the coronary occlusion. A quick temperature drop is defined as a significant drop in distal coronary temperature (<5 °C) within 5 minutes after start of the infusion. * After reaching the targeted temperature, is it possible to obtain a stable coronary temperature during 20 minutes. * How long is he Door-to-balloon time delayed
1 secondary outcome
Time to target temperature in seconds
Time frame: 0 - 20
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 22 Nov 2016.
- Background: PubMed 22131353Tissier R, Ghaleh B, Cohen MV, Downey JM, Berdeaux A. Myocardial protection with mild hypothermia. Cardiovasc Res. 2012 May 1;94(2):217-25. doi: 10.1093/cvr/cvr315. Epub 2011 Nov 29.
- Background: PubMed 26269225Otterspoor LC, Van't Veer M, van Nunen LX, Wijnbergen I, Tonino PA, Pijls NH. Safety and feasibility of local myocardial hypothermia. Catheter Cardiovasc Interv. 2016 Apr;87(5):877-83. doi: 10.1002/ccd.26139. Epub 2015 Aug 13.
- Individual participant dataSharing planned: Yes. by publishing the results in a peer reviewed journal
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing intracoronary infusion with saline on 22 and 4°C in people with Myocardial Infarction, run by Catharina Ziekenhuis Eindhoven at 1 site in Netherlands.
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 10 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 22 Nov 2016. 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 Netherlands. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
arrhythmia or AV-block (1st, 2nd or 3rd degree) (time frame: 0 - 20 minutes). The study lists 2 primary outcomes in all. 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 NCT02753478, which also lists 2 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 22 Nov 2016.