Clinical trial NCT02313961: Remote Ischemic Conditioning in ST-elevation Myocardial Infarction as Adjuvant to Primary Angioplasty
Official title: Evaluation of Remote Ischemic Conditioning in ST-elevation Myocardial Infarction as Adjuvant to Primary Angioplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ST Elevation Myocardial Infarction
Keywords: ST elevation myocardial infarction
Reperfusion injury
Remote ischaemic conditioning
Lead sponsor: Hospital de Braga
Sponsor class: OTHER
Collaborators: name: Universidade do Porto
First posted: 2014-12-10
Enrollment: 516
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the RIC-STEMI trial is to assess whether remote ischaemic conditioning (RIC) as an adjunctive therapy during primary percutaneous coronary intervention (PCI) in patients presenting with ST-elevation myocardial infarction (STEMI) can improve clinical outcomes as assessed by death from cardiac-cause or hospitalization for heart failure (HF) for a minimum follow-up period of 12 months.

Detailed description: Ischemic heart disease (IHD) is the leading cause of mortality worldwide, accounting for over 7 million deaths per year. ST-elevation myocardial infarction (STEMI) accounts for nearly one third of acute coronary syndromes. Despite improved STEMI patient care achieved mainly by timely primary percutaneous coronary intervention (PCI) mortality remains unacceptably high, ranging between 6 and 14%. High mortality rates may partly be ascribed to ischemia-reperfusion injury (IRI) which is believed to account for up to 40-50% of infarct size. Several pharmacological alternatives have been attempted to prevent IRI in promising animal experiments nevertheless clinical translation has been disappointing. On the opposite side, ischemic conditioning (IC) by short cycles of ischemia-reperfusion applied before, during or after a major ischemic event has clearly been shown to attenuate IRI in various clinical scenarios. Moreover, even repeated bouts of limb ischemia are cardioprotective, so-called remote IC (RIC). In 2010, Bøtker et al. showed improved myocardial salvage index as assessed by single photon emission computed tomography 30 days after PCI in patients randomly assigned to receive concomitant RIC whereas Rentoukas et al. found higher proportions of ST-segment resolution with adjunctive RIC compared with PCI alone, although significant reductions in troponin I peaks only reached statistical significance in a subgroup undergoing both RIC and morphine therapy combined with PCI. More recently, the group of Bøtker evaluated the long-term effect of RIC on the very same population they initially recruited (166 patients underwent PCI with adjunctive RIC and 167 patients simply underwent PCI) and showed improved long-term prognosis for patients that underwent adjunctive RIC as regards the composite endpoint of adverse cardiac and cerebrovascular events: all-cause mortality, MI, readmission for heart failure (HF), and ischaemic stroke/transient ischaemic attack. However, although very promising, their results are inconclusive as regards cardiovascular mortality and HF development, since the study was not powered to show differences in these clinical events. Large scale studies addressing major adverse cardiovascular events are warranted.

RIC-STEMI is a single-centre, randomized, controlled trial to assess whether RIC as an adjunctive therapy during primary PCI in patients presenting with ST-elevation myocardial infarction (STEMI) can improve clinical outcomes as assessed by death from cardiac-cause or hospitalization for heart failure (HF) for a minimum follow-up period of 12 months.

After enrollment, participants are randomized according to a computer-generated randomization schedule, in a ratio of 1:1 to RIC or no intervention, in blocks of four individuals. RIC is begun at least 10 min before the estimated time of first balloon inflation and its maximum duration is 30 min. Ischemia is induced by 3 cycles of inflation of a blood pressure cuff placed on the left lower limb to 200 mmHg and then deflation to 0 mmHg for another 5 minutes. Apart from temporary moderate pain in the treated thigh, RIC has been shown innocuous.

All patients receive standard of care therapy according to institutional guidelines, namely treatment with 250 mg aspirin intravenously, 600 mg clopidogrel orally and 5000 IU unfractioned heparin intravenously before PCI. The choice of balloons, stent types and PCI procedure as well as the use of glycoprotein IIb/IIIa inhibitors are left to the discretion of the attending physician.

Considering that STEMI is a medical emergency, little time is available. Eligible patients are orally informed and asked to participate in the study. Enrollment will be based on witnessed oral consent and only after the acute phase has been dealt with will a full written informed consent be obtained. Patients are notified at enrollment of their freedom to abandon the study at any time without consequences.

Eligibility criteria: Inclusion Criteria:

* STEMI defined as chest pain (or epigastric pain) for more than 30 minutes and either: (i) new ST elevation at the J point in two contiguous leads with the cut-off points of ≥0.2 mV in men or ≥0.15 mV in women in leads V2-V3 or ≥0.1 mV in all other leads, (ii) or new or presumed new left bundle branch block (LBBB)
* Symptom onset not more than 12 h before presentation
* Willingness and capability to provide informed consent

Exclusion Criteria:

* Cardiogenic shock as defined by systemic hypotension (systolic arterial pressure - SAP - below 90 mmHg) and evidence of tissue hypoperfusion
* Post-cardiac arrest status
* Need for mechanical ventilation
* Known peripheral artery disease or evidence of lower limb ischemia
* Recent myocardial infarction (within 30 days)

Primary outcomes:
measure: Combined outcome of death from cardiac cause or hospitalization for HF on follow-up, including device implantation (implantable cardioverter defibrillator, cardiac resynchronization and left ventricular assist device).
timeFrame: Minimum follow up of 12 months
Secondary outcomes:
measure: MI size.
timeFrame: Index hospitalization.
measure: Left ventricular function.
timeFrame: Index hospitalization.
measure: Acute kidney injury.
timeFrame: Index hospitalization.
measure: Major adverse cardiovascular events
timeFrame: Minimum follow up of 12 months
Other outcomes:
Locations:
city: Braga
country: Portugal
facility: Hospital of Braga
state: Minho
Study officials:
affiliation: Hospital of Braga
name: António Gaspar, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, Clarke SC, Shapiro LM, Schofield PM, O'Sullivan M, Dutka DP. Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial. Circulation. 2009 Feb 17;119(6):820-7. doi: 10.1161/CIRCULATIONAHA.108.809723. Epub 2009 Feb 2.
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citation: Rentoukas I, Giannopoulos G, Kaoukis A, Kossyvakis C, Raisakis K, Driva M, Panagopoulou V, Tsarouchas K, Vavetsi S, Pyrgakis V, Deftereos S. Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action. JACC Cardiovasc Interv. 2010 Jan;3(1):49-55. doi: 10.1016/j.jcin.2009.10.015.
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citation: Gaspar A, Pereira MA, Azevedo P, Lourenco A, Marques J, Leite-Moreira A. Remote ischemic conditioning in ST-elevation myocardial infarction as adjuvant to primary angioplasty (RIC-STEMI): study protocol for a randomized controlled trial. Trials. 2015 Sep 8;16:398. doi: 10.1186/s13063-015-0937-1.