ST-elevation Acute Myocardial InfarctionNCT02732080
Gradual Versus Abrupt Reperfusion in Primary PCI (GUARD)
A study testing deferred coronary stenting and immediate stenting in people with ST-elevation Acute Myocardial Infarction, run by Istanbul University at 2 sites in Turkey (Türkiye).
Trial summary
After reopening of the infarct related artery by primary percutaneous coronary interventions (PPCI), microvascular damage at the related myocardial territory is not terminated immediately. This ongoing nature of microvascular damage leading to myocardial malperfusion is related to final infarct size. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- ST-elevation Acute Myocardial Infarction
- What is being tested?
- deferred coronary stenting and immediate stenting
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesTurkey (Türkiye)
- Study dates
- Apr 2016to 30 Dec 2018
- Phase
- Interventional
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients presenting with ST-elevation acute myocardial infarction (STEMI) within 12 hours of their symptom onset in whom TIMI-3 flow was established in infarct related artery (IRA) after balloon angioplasty or thrombectomy.
Who cannot join
- Recanalized (TIMI I-III flow) IRA at coronary angiography.
- Patients in whom TIMI-3 flow was not able to be established after wire crossing, balloon angioplasty or thrombectomy.
- STEMI due to bypass-graft occlusion
- Severe heart failure or cardiogenic shock
Trial locations and contacts
2 sites in 1 country.
Turkey (Türkiye)2 sites
Istanbul University, Istanbul Faculty of Medicine, Department of Cardiology
Istanbul, 34290
Istanbul University School of Medicine
Istanbul
About this study
Official title: Effect of Gradual Reperfusion on Myocardial Edema and Coronary Microvascular Integrity in Patients Undergoing Primary Percutaneous Coronary Intervention
After reopening of the infarct related artery by primary percutaneous coronary interventions (PPCI), microvascular damage at the related myocardial territory is not terminated immediately. This ongoing nature of microvascular damage leading to myocardial malperfusion is related to final infarct size. However, time course of the microvascular impairment /obstruction after PPCI in patients presented with ST-elevating acute myocardial infarction (STEMI) is not known. Routine primary percutaneous coronary interventions (PPCI) for ST-elevation acute myocardial infarction (STEMI) includes balloon angioplasty (or thrombectomy) followed immediately by stent implantation. However, stent implantation performed in this thrombotic setting may lead to a further microvascular damage by causing more distal embolisation and by inducing distal microvascular spasm by stretching the coronary vessel wall. Furthermore, sudden exposure of distal microcirculation to a high distal intracoronary pressure achieved by immediate stent implantation may exaggerate myocardial oedema which contributes microvascular damage substantially by external compression. However, results of studies investigating the efficacy of delayed stenting (24-48 hours later) in patients in whom TIMI -3 flow was achieved after balloon angioplasty were inconsistent.
In this study, STEMI patients undergoing PPCI, in whom epicardial reperfusion was achieved (TIMI-3 flow) by wire crossing or by balloon angioplasty or aspiration thrombectomy, will be randomised to immediate and delayed stenting groups. Delayed stenting will be performed at the time when coronary auto regulation was recovered which is going to be determined based on the continuous intracoronary hemodynamic monitoring after reperfusion.
Read the detailed description
It was shown in ischemia/reperfusion models that after reopening of the occluded epicardial coronary artery, following initial hyperemic flow, myocardial blood flow in the area at risk rapidly and progressively declines and get stabilised approximately within 30 minutes.This finding implies that, in spite of the initial ischemic insult, coronary auto-regulation in the reperfused myocardial territory recovers. Nevertheless, this recovery requires some time after reperfusion was achieved. During total occlusion of an epicardial coronary artery, pre-arteriolar sphincters can be expected to be paralysed in widely open position in response to severely increased distal myocardial demand. Ischemic myocyte damage also contributes to malfunctioned pre-arteriolar sphincters. Therefore, full restoration of perfusion pressure distal to the infarct related artery by immediate stenting (direct or after angioplasty) may then fail to induce an immediate adaptive autoregulatory response (compensatory vasoconstriction) in the related microvascular territory, resulting in an inappropriately increased pressure in the damaged microcirculation. During total epicardial occlusion, ischemia/hypoxia induced damage and increased permeability at the capillary level lead to loss of structural integrity in the related microvascular territory. After immediate stenting, this severely damaged microcirculation is exposed to a suddenly increased uncontrolled intracoronary pressure which may consequently substantially contribute to intramyocardial haemorrhage and oedema.
Therefore, it was hypothesised that gradual reperfusion with delayed stenting performed when coronary auto regulatory function was recovered may lessen the myocardial oedema and/or haemorrhage by preventing/limiting uncontrolled increase in pressure in the distal microcirculation.
The recovery of coronary autoregulatory function in reperfused STEMI patients can be assessed by continuous monitoring of coronary (microvascular) blood flow and resistance values after restoration of epicardial blood flow by balloon angioplasty in individual basis.
In this study, following establishment of TIMI-3 flow by balloon angioplasty, patients will be randomized to immediate or delayed stenting groups. Continuous intracoronary hemodynamic monitorization will be performed in re-opened infarct related artery using a coronary guide wire equipped with pressure and flow sensors for a total of 1hour in both groups.
In delayed stent group, stent implantation will be performed in individual basis when coronary hemodynamic data indicates that coronary autoregulation was recovered (when initial hyperaemic flow response was subsided and baseline microvascular resistance was increased). Recovery of autoregulatory function will be determined by identification of stabilisation of baseline coronary flow velocity and baseline microvascular resistance in infarct related artery after balloon angioplasty. Stabilization will be decided by comparing basal coronary flow velocity and microvascular resistance values measured in non-infarct related coronary artery immediately before PPCI with the values that was being measured in re-opened infarct related artery. When baseline flow velocity and resistance values being recorded in IRA got close to the values measured in non-IRA, IRA will be stented. Intracoronary pressure and flow data will continuously be monitored until the end of 1 hour follow-up period.
In immediate stenting group, stent implantation will be performed immediately following angioplasty. Intracoronary pressure and flow data will continuously be monitored using dual sensor coronary guide wire until the end of 1 hour follow up period.
- Conditions
- ST-elevation Acute Myocardial Infarction
- Being tested
- deferred coronary stenting, immediate stenting
- Keywords
- primary percutaneous coronary intervention, microvascular obstruction, myocardial edema, microvascular resistance, acute myocardial infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
deferred coronary stentingDevice
Final coronary stenting will be performed when coronary auto regulation was recovered (approximately 30 minutes after establishment of TIMI III flow şn the infarct related artery)
immediate stentingDevice
Stent implantation will be performed immediately after balloon angioplasty (or thrombectomy or wire crossing) as it is performed in daily routine.
| Study group | Role | What they receive |
|---|---|---|
| Deferred coronary stenting | Experimental | In this arm, after establishing TIMI -3 flow in infarct related artery with balloon angioplasty, patients will undergo stent implantation when coronary autoregulatory function was recovered (initial hyperemic flow was subsided and baseline resistance was increased). Recovery of the auto regulatory function will be determined by measuring microvascular flow and resistance. After stenting microvascular flow / resistance will continue to be monitored using pressure/flow sensor tipped guide wire until the completion of 1 hour follow up period. Receives: Device: deferred coronary stenting |
| Immediate stenting | Active comparator | In this arm, patients will undergo stenting immediately after balloon angioplasty. After stent implantation, microvascular flow / resistance values will be continuously monitored using pressure/flow sensor tipped guide wire until the end of 1 hour follow up period. Receives: Device: immediate stenting |
What is being measured
The primary outcome is the main question the study is designed to answer.
Coronary zero flow pressure (Pzf)
Measured: At the end of the 1 hour intracoronary hemodynamic monitorization
Secondary outcomes (1)
Hyperemic microvascular resistance (HMR)
Measured: At the end of the completion of 1 hour intracoronary hemodynamic monitorization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2016 (estimated)
- Study startApr 2016
- Primary completion30 Dec 2018
- Study completion30 Dec 2018
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 ST-elevation Acute Myocardial InfarctionStudies of the same condition, open and under way.
- More trials run by Istanbul UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istanbul University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Murat Sezer, Istanbul University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02732080
- Sponsor's protocol ID
- 373
- Status last verified
- Feb 2023
- First submitted
- 30 Mar 2016
- Last updated
- 1 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Sezer M, Tas A, Demirtakan ZG, Broyd CJ, Ozcan A, Hasdemir H, Kocaaga M, Sezer I, Sonsoz MR, Atici A, Ozcan I, Umman B, Bugra Z, Davies JE, Escaned J, van Royen N, Umman S. Coronary microcirculation in nonculprit vessel territory in reperfused acute myocardial infarction. Microvasc Res. 2023 May;147:104495. doi: 10.1016/j.mvr.2023.104495. Epub 2023 Feb 3.
PubMed 36739961Sezer M, Escaned J, Broyd CJ, Umman B, Bugra Z, Ozcan I, Sonsoz MR, Ozcan A, Atici A, Aslanger E, Sezer ZI, Davies JE, van Royen N, Umman S. Gradual Versus Abrupt Reperfusion During Primary Percutaneous Coronary Interventions in ST-Segment-Elevation Myocardial Infarction (GUARD). J Am Heart Assoc. 2022 May 17;11(10):e024172. doi: 10.1161/JAHA.121.024172. Epub 2022 May 16.
PubMed 35574948
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Gradual Reperfusion on Myocardial Edema and Coronary Microvascular Integrity in Patients Undergoing Primary Percutaneous Coronary Intervention
- ClinicalTrials.gov ID
- NCT02732080
- Acronym / sponsor ID
- 373
- Conditions
- ST-elevation Acute Myocardial Infarction
- Keywords
- primary percutaneous coronary intervention, microvascular obstruction, myocardial edema, microvascular resistance, acute myocardial infarction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Istanbul UniversityUniversity, hospital or other
- Study start
- Apr 2016
- Primary completion
- 30 Dec 2018 (actual)
- Study completion
- 30 Dec 2018 (actual)
- First posted
- 8 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.
After reopening of the infarct related artery by primary percutaneous coronary interventions (PPCI), microvascular damage at the related myocardial territory is not terminated immediately. This ongoing nature of microvascular damage leading to myocardial malperfusion is related to final infarct size. However, time course of the microvascular impairment /obstruction after PPCI in patients presented with ST-elevating acute myocardial infarction (STEMI) is not known. Routine primary percutaneous coronary interventions (PPCI) for ST-elevation acute myocardial infarction (STEMI) includes balloon angioplasty (or thrombectomy) followed immediately by stent implantation. However, stent implantation performed in this thrombotic setting may lead to a further microvascular damage by causing more distal embolisation and by inducing distal microvascular spasm by stretching the coronary vessel wall. Furthermore, sudden exposure of distal microcirculation to a high distal intracoronary pressure achieved by immediate stent implantation may exaggerate myocardial oedema which contributes microvascular damage substantially by external compression. However, results of studies investigating the efficacy of delayed stenting (24-48 hours later) in patients in whom TIMI -3 flow was achieved after balloon angioplasty were inconsistent.
In this study, STEMI patients undergoing PPCI, in whom epicardial reperfusion was achieved (TIMI-3 flow) by wire crossing or by balloon angioplasty or aspiration thrombectomy, will be randomised to immediate and delayed stenting groups. Delayed stenting will be performed at the time when coronary auto regulation was recovered which is going to be determined based on the continuous intracoronary hemodynamic monitoring after reperfusion.
Detailed description
It was shown in ischemia/reperfusion models that after reopening of the occluded epicardial coronary artery, following initial hyperemic flow, myocardial blood flow in the area at risk rapidly and progressively declines and get stabilised approximately within 30 minutes.This finding implies that, in spite of the initial ischemic insult, coronary auto-regulation in the reperfused myocardial territory recovers. Nevertheless, this recovery requires some time after reperfusion was achieved. During total occlusion of an epicardial coronary artery, pre-arteriolar sphincters can be expected to be paralysed in widely open position in response to severely increased distal myocardial demand. Ischemic myocyte damage also contributes to malfunctioned pre-arteriolar sphincters. Therefore, full restoration of perfusion pressure distal to the infarct related artery by immediate stenting (direct or after angioplasty) may then fail to induce an immediate adaptive autoregulatory response (compensatory vasoconstriction) in the related microvascular territory, resulting in an inappropriately increased pressure in the damaged microcirculation. During total epicardial occlusion, ischemia/hypoxia induced damage and increased permeability at the capillary level lead to loss of structural integrity in the related microvascular territory. After immediate stenting, this severely damaged microcirculation is exposed to a suddenly increased uncontrolled intracoronary pressure which may consequently substantially contribute to intramyocardial haemorrhage and oedema.
Therefore, it was hypothesised that gradual reperfusion with delayed stenting performed when coronary auto regulatory function was recovered may lessen the myocardial oedema and/or haemorrhage by preventing/limiting uncontrolled increase in pressure in the distal microcirculation.
The recovery of coronary autoregulatory function in reperfused STEMI patients can be assessed by continuous monitoring of coronary (microvascular) blood flow and resistance values after restoration of epicardial blood flow by balloon angioplasty in individual basis.
In this study, following establishment of TIMI-3 flow by balloon angioplasty, patients will be randomized to immediate or delayed stenting groups. Continuous intracoronary hemodynamic monitorization will be performed in re-opened infarct related artery using a coronary guide wire equipped with pressure and flow sensors for a total of 1hour in both groups.
In delayed stent group, stent implantation will be performed in individual basis when coronary hemodynamic data indicates that coronary autoregulation was recovered (when initial hyperaemic flow response was subsided and baseline microvascular resistance was increased). Recovery of autoregulatory function will be determined by identification of stabilisation of baseline coronary flow velocity and baseline microvascular resistance in infarct related artery after balloon angioplasty. Stabilization will be decided by comparing basal coronary flow velocity and microvascular resistance values measured in non-infarct related coronary artery immediately before PPCI with the values that was being measured in re-opened infarct related artery. When baseline flow velocity and resistance values being recorded in IRA got close to the values measured in non-IRA, IRA will be stented. Intracoronary pressure and flow data will continuously be monitored until the end of 1 hour follow-up period.
In immediate stenting group, stent implantation will be performed immediately following angioplasty. Intracoronary pressure and flow data will continuously be monitored using dual sensor coronary guide wire until the end of 1 hour follow up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Deferred coronary stenting | Experimental | Device: deferred coronary stentingIn this arm, after establishing TIMI -3 flow in infarct related artery with balloon angioplasty, patients will undergo stent implantation when coronary autoregulatory function was recovered (initial hyperemic flow was subsided and baseline resistance was increased). Recovery of the auto regulatory function will be determined by measuring microvascular flow and resistance. After stenting microvascular flow / resistance will continue to be monitored using pressure/flow sensor tipped guide wire until the completion of 1 hour follow up period. |
| Immediate stenting | Active comparator | Device: immediate stentingIn this arm, patients will undergo stenting immediately after balloon angioplasty. After stent implantation, microvascular flow / resistance values will be continuously monitored using pressure/flow sensor tipped guide wire until the end of 1 hour follow up period. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients presenting with ST-elevation acute myocardial infarction (STEMI) within 12 hours of their symptom onset in whom TIMI-3 flow was established in infarct related artery (IRA) after balloon angioplasty or thrombectomy.
Key exclusion criteria (4 listed)
- Recanalized (TIMI I-III flow) IRA at coronary angiography.
- Patients in whom TIMI-3 flow was not able to be established after wire crossing, balloon angioplasty or thrombectomy.
- STEMI due to bypass-graft occlusion
- Severe heart failure or cardiogenic shock
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 |
|---|---|---|
| deferred coronary stentingFinal coronary stenting will be performed when coronary auto regulation was recovered (approximately 30 minutes after establishment of TIMI III flow şn the infarct related artery) | Device | Deferred coronary stenting |
| immediate stentingStent implantation will be performed immediately after balloon angioplasty (or thrombectomy or wire crossing) as it is performed in daily routine. | Device | Immediate stenting |
Primary outcome
Coronary zero flow pressure (Pzf)
Time frame: At the end of the 1 hour intracoronary hemodynamic monitorization
1 secondary outcome
Hyperemic microvascular resistance (HMR)
Time frame: At the end of the completion of 1 hour intracoronary hemodynamic monitorization
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 1 Mar 2023.
- Derived from this study: PubMed 36739961Sezer M, Tas A, Demirtakan ZG, Broyd CJ, Ozcan A, Hasdemir H, Kocaaga M, Sezer I, Sonsoz MR, Atici A, Ozcan I, Umman B, Bugra Z, Davies JE, Escaned J, van Royen N, Umman S. Coronary microcirculation in nonculprit vessel territory in reperfused acute myocardial infarction. Microvasc Res. 2023 May;147:104495. doi: 10.1016/j.mvr.2023.104495. Epub 2023 Feb 3.
- Derived from this study: PubMed 35574948Sezer M, Escaned J, Broyd CJ, Umman B, Bugra Z, Ozcan I, Sonsoz MR, Ozcan A, Atici A, Aslanger E, Sezer ZI, Davies JE, van Royen N, Umman S. Gradual Versus Abrupt Reperfusion During Primary Percutaneous Coronary Interventions in ST-Segment-Elevation Myocardial Infarction (GUARD). J Am Heart Assoc. 2022 May 17;11(10):e024172. doi: 10.1161/JAHA.121.024172. Epub 2022 May 16.
- Individual participant dataSharing planned: Undecided
Related trials for ST-elevation Acute Myocardial Infarction
RecruitingPhase 4
Early Single Antiplatelet Therapy After IVUS-Guided PCI in Acute Coronary Syndrome
Acute Coronary Syndromes, STEMI
Active, not recruiting
Physiology-guided vs Angiography-guided Non-culprit Lesion Complete Revascularization for Acute MI & Multivessel Disease
Acute Myocardial Infarction, Coronary Artery Disease
Not yet recruitingObservational study
AI-ECG Detection of Occlusion Myocardial Infarction at Emergency Department Triage (TRIACS)
Acute Coronary Syndromes, Chest Pain
RecruitingObservational study
Analysis of Life-threatening ARrhythMias After Acute Coronary Syndrome
Acute Coronary Syndromes (ACS), Ventricular Tachycardia (VT)
Not yet recruitingObservational study
On vs Off-hour PPCI in STEMI Patients
Acute STEMI, PPCI
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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing deferred coronary stenting and immediate stenting in people with ST-elevation Acute Myocardial Infarction, run by Istanbul University at 2 sites in Turkey (Türkiye).
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 1 inclusion and 4 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 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Turkey (Türkiye). 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.
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?
Coronary zero flow pressure (Pzf) (time frame: At the end of the 1 hour intracoronary hemodynamic monitorization). 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 NCT02732080, 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 1 Mar 2023; AzTrials last refreshed its copy on 6 Nov 2026.