Remote Ischemic Conditioning in ST-elevation Myocardial Infarction as Adjuvant to Primary Angioplasty

NCT ID: NCT02313961

Last Updated: 2019-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 516 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2018-12-31

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.

Conditions

ST Elevation Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RIC patients

Subjects submitted to remote ischaemic conditioning (RIC)

Group Type: EXPERIMENTAL

Remote ischaemic conditioning

Intervention Type: OTHER

Remote ischaemic conditioning is induced by 3 cycles of manual inflation of a blood pressure cuff placed on the left lower limb to 200 mmHg for 5 minutes and then deflation to 0 mmHg for another 5 minutes.

No RIC patients

Subjects not submitted to remote ischaemic conditioning (RIC)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Remote ischaemic conditioning

Remote ischaemic conditioning is induced by 3 cycles of manual inflation of a blood pressure cuff placed on the left lower limb to 200 mmHg for 5 minutes and then deflation to 0 mmHg for another 5 minutes.

Intervention Type: OTHER

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidade do Porto

OTHER

Sponsor Role: collaborator

Hospital de Braga

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

António Gaspar, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital of Braga

Locations

Hospital of Braga

Braga, Minho, Portugal

Countries

Portugal

References

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Reference Type: DERIVED

PMID: 26350480 (View on PubMed)

Other Identifiers

HB-CARD-01

Identifier Type: -

Identifier Source: org_study_id