Remote Postconditioning in Patients With Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention (PCI) (RemPostCon)

Pilot Study to Test Feasibility, Safety, Molecular Mediators and Preliminary Efficacy of Remote Myocardial Postconditioning Provided With Extrinsic Cuff Compression of Lower Limb During Primary PCI

Background: Experimental studies suggest that remote limb ischaemic postconditioning (RemPostCon) can reduce infarct size in pigs. Initial clinical applications support the beneficial role of RemPostCon in preserving endothelial function during upper limb ischemia in healthy volunteers and in patients with stable coronary artery disease.

Aim of the study: To evaluate the feasibility, safety and efficacy of RemPostCon in the setting of STEMI and primary PCI (pPCI) and to investigate potential circulating mediators of its effects.

Patients and methods: Patients who undergo pPCI for anterior STEMI within 6 hours since the onset of symptoms are randomly assigned to receive either RemPostCon + pPCI or pPCI alone in a single-blind fashion. All patients receive therapy according to the current international guidelines. Three cycles of ischemia-reperfusion are provided to the lower limb inflating a cuff to 200 mmHg. Each cycle consists of 5' of ischaemia, followed by 5' of reperfusion. RemPostCon is started at the time of angioplasty in the infarct related artery. Primary endpoint is the area under the curve (AUC) of creatinine kinase - MB (CK - MB). Cardiac magnetic resonance (CMR) is performed early before discharge and 4 months after the event, if there are no contraindications.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury
• Intervention / Treatment: Procedure: Remote Postconditioning

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Italy
  • Genoa, Italy, 16100
    • ASL3 Genovese, Villa Scassi Hospitale
  • Pavia, Italy, 27100
    • IRCCS Policlinico San Matteo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >= 18 yrs AND Age =< 80 yrs
• STEMI definition
• Pain to door time < 6 hrs
• Killip class 1 - 2 - 3
• Initial TIMI flow 0 - 1 in the anterior descending artery
• Signed informed consent

Exclusion Criteria:

• Pregnancy
• Cardiogenic shock
• Initial TIMI flow 2 - 3 in the anterior descending artery
• History of prior MI in the past 6 months
• History of prior CABG
• History of peripheral vascular disease III - IV grade
• History of abdominal Aortic Aneurysm > 5 cm
• Severe coronaropathy that could condition further revascularization before the end of the study
• Other relevant medical or surgical conditions that can influence prognosis at 4 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: RemotePostConditioning; Patients will receive pPCI and treatments according to guidelines for STEMI PLUS extrinsic cuff compression to the lower limb for 5 ' followed by 5' reperfusion for three cycles (30' in total) starting with myocardial reperfusion	Procedure: Remote Postconditioning; Lower limb compression using a cuff inflated to 200 mmHg for 5 ' followed by 5' of reperfusion fo three times during 30'
Sham Comparator: Controls; pPCI and treatments according to guidelines for STEMI	Procedure: Remote Postconditioning; Lower limb compression using a cuff inflated to 200 mmHg for 5 ' followed by 5' of reperfusion fo three times during 30'

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve of CK - MB release	baseline to 72h since admission

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve of CK release	baselinte to 72h since admission
TIMI Frame Count	30 minutes after first balloon inflation in infarct-related artery
Time to balloon	during pPCI
Ejection Fraction MRI	before discharge and after 4 months
Myocardial Blush grading	30 minutes after first balloon inflation
ST segment resolution	6h after balloon
Troponin I peak	72h since admission
Mortality rate	4 months since admission
artero-venous differences in pO2, pCO2, pH, HCo3	baseline and 30 minutes after first balloon inflation
Major adverse cardiac events	4 months since admission
artero-venous quantitative and qualitative differences in endothelial progenitors cells (subgroups)	within 24 h since admission
artero-venous Differences of Cytokines	within 24h since admission
Edema Volume T2 sequences MRI	before discharge
Delay enhancement volume MRI	before discharge and after 4 months

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Matteo
• Investigators: Study Director: Maurizio Ferrario, MD, IRCCS Policlinico San Matteo; Principal Investigator: Gabriele Crimi, MD, IRCCS Policlinico San Matteo

Publications and helpful links

General Publications

• Crimi G, Pica S, Raineri C, Bramucci E, De Ferrari GM, Klersy C, Ferlini M, Marinoni B, Repetto A, Romeo M, Rosti V, Massa M, Raisaro A, Leonardi S, Rubartelli P, Oltrona Visconti L, Ferrario M. Remote ischemic post-conditioning of the lower limb during primary percutaneous coronary intervention safely reduces enzymatic infarct size in anterior myocardial infarction: a randomized controlled trial. JACC Cardiovasc Interv. 2013 Oct;6(10):1055-63. doi: 10.1016/j.jcin.2013.05.011.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: March 18, 2009
• First Submitted That Met QC Criteria: March 18, 2009
• First Posted (Estimate): March 19, 2009

Study Record Updates

• Last Update Posted (Estimate): August 17, 2012
• Last Update Submitted That Met QC Criteria: August 16, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Primary PCI; Myocardial Infarction; Remote Postconditioning; Myocardial reperfusion Injury
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Cardiomyopathies; Myocardial Infarction; Infarction; Myocardial Ischemia; Ischemia; Reperfusion Injury; Myocardial Reperfusion Injury
• Other Study ID Numbers: RemPostConditioning