Effect of RIC on Clinical Outcomes in STEMI Patients Undergoing pPCI

Myocardial Reperfusion Injury Clinical Trial

— CONDI2  

Official title:

Effect of Remote Ischaemic Conditioning on Clinical Outcomes in ST-elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: A Multinational Multicentre Randomised Controlled Clinical Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01857414
• Other study ID #: Condi2-37747
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 2013
• Est. completion date: September 2019

Study information

• Verified date: March 2018
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the the study is to investigate whether Remote Ischaemic Conditioning (RIC) can improve clinical outcomes (cardiac death and hospitalisation for heart failure) at one year in patients presenting with ST-elevation Myocardial Infarction and undergoing primary percutaneous coronary intervention. This will be done in a multinational investigator-driven, multi-centre, randomised, controlled, single-blind, parallel assignment, prospective clinical efficacy trial.

Description:

Coronary heart disease (CHD) is the leading cause of death in Denmark and Europe, accounting for 1.92 million deaths in Europe per year: over one in five men (21%) and one in five women (22%) die from CHD.

Patients presenting with a ST-elevation Myocardial Infarction (STEMI)have despite advanced treatment with primary percutaneous coronary intervention (pPCI) a significant mortality and morbidity at one year with 17.4% of patients dying from a cardiovascular cause or being hospitalised from heart failure.

Remote Ischaemic Conditioning (RIC) applied at the time of myocardial reperfusion can reduce myocardial infarct size, confirming the existence of myocardial reperfusion injury. In this respect, RIC has been shown to limit myocardial infarct size and preserve cardiac function in STEMI patients undergoing pPCI.

RIC is performed in the ambulance during transport to the PCI unit by cycles of inflations of a blood pressure cuff to induce four 5-minute cycles of limb ischaemia and reperfusion. The method is virtually cost-free non-pharmacological and non-invasive therapeutic strategy.

Hypothesis:

RIC followed by pPCI improves clinical outcomes in STEMI patients when compared to STEMI controls undergoing standard pPCI evaluated one year post PCI.

Trial Design and aim:

Multinational investigator-driven, multi-centre, randomized, controlled, single-blind (Outcomes Assessor), parallel assignment, prospective clinical efficacy trial. A total of 2600 patients are to be included over a 36 months period.

Overall primary objective To determine whether RIC improves clinical outcomes (Cardiac mortality and hospitalisation for heart failure) at one year in 2600 STEMI patients undergoing pPCI.

Secondary objectives:

To determine, in the pre-specified subgroups, whether age, gender, diabetes, and duration of chest pain to PCI influence the response to RIC.

To determine whether RIC preserves left ventricular function measured by echocardiography after three months post pPCI.

Study progress The patient will be informed and treated according to the national and international guidelines for Good Clinical Practice and protected under the Act concerning the processing of personal data and health law.

The admitting ambulance doctor or doctor at the receiving hospital will orally inform the patient and hand out the approved short written information. After information is given in the acute phase the patient does not have much time for reflection before signing the informed consent form.

Therefore a full written information and additional oral information will be given to the patient after the acute phase by a study nurse or the doctor performing the pPCI. As well during the first and second stage of information it will be emphasised that the patient has the right to withdraw his/her informed consent at any time.

After informed consent is obtained the patient will be randomised via a secure web-site to either pPCI with or without RIC by the the doctor on duty at the receiving hospitals. Computer-generated blocked randomisation lists, stratified by centre, will be prepared in advance of the study.

pPCI incl. the use of stents and antithrombotic regimens will be performed according to standard procedures at the treating hospital.

Blood samples (acute, 6-8, 24 and 48-72 hours after pPCI will be drawn during the acute phase at the treating hospital or at the local hospital.

Three days after pPCI an echocardiography (ECCO) will be performed at the hospital. Further three months after pPCI an ECCO will be performed at the hospital.

Information regarding re-hospitalisation or death will be drawn from electronic patient chart.

Benefit of the study Potential benefits: Participating patients will be offered an extra clinical out patient control, incl. an echocardiography three months after pPCI.

Disadvantage: In relation to the inflation of the blood pressure cuff temporary moderate pains in the treated arm might occur. Otherwise, the RIC has previously been proven to be without side effects.

An extra blood sampling of app. 15 ml will be drawn 48-72 hours after pPCI. A small but insignificant risk of local infection in relation to this is a risk.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2613
• Est. completion date: September 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female patients (>18 years old) presenting with chest pain for more than 30 minutes

• Suspected STEMI (ST-elevation at the J-point in two contiguous leads with the cut-off points: =0.2 millivolt (mV) in men or =0.15 mV in women in leads V2-V3 and/ or =0.1 mV in other leads)

• Informed consent obtained

• Life expectancy of more than 1 year

Exclusion Criteria:

• Previous by-pass surgery

• MI or treatment with thrombolysis within 30 days

• New left bundle branch block

• Patients treated with cooling

• Paresis of upper limb

• A-V shunt

Related Conditions & MeSH terms

• Myocardial Infarction
• Myocardial Reperfusion Injury
• Reperfusion Injury
• ST Elevation Myocardial Infarction

Intervention

Procedure:
• Remote Ischaemic Conditioning (RIC)
The CellAegis auto RIC (automated blood pressure cuff) will be placed on the upper arm and inflate to 200 mmHg for 5 minutes followed by 5 minutes of deflations. The programmed cycle is repeated 4 times in total, summing up to a total treatment length of 35 minutes).In recruiting centres where randomisation occurs at the hospital or in cases with short transportation time, the RIC protocol will continue during PCI until successful or until immediately before reperfusion.

Locations

Country	Name	City	State
Denmark	The Heart Centre, Aalborg Sygehus	Aalborg
Denmark	Department of Cardiology, Aarhus University Hospital, Skejby	Aarhus
Denmark	The Heart Centre, Rigshospitalet, Copenhagen University	Copenhagen
Denmark	Department of Cardiology, Odense University Hospital	Odense
Serbia	Military Medical Academy, Belgrade	Belgrade
Serbia	The Clinical Center of Serbia	Belgrade
Spain	Hospital Universitario Central de Asturias	Oviedo
United Kingdom	The Hatter Cardiovascular Institute, University College London	London

Sponsors (13)

Lead Sponsor

Collaborator

Aarhus University Hospital

Aalborg Universitetshospital, Central Denmark Region, Clinical Centre of Serbia, Hospital Universitario Central de Asturias, Military Medical Academy, Belgrade, Serbia, Odense University Hospital, Prehospital Emergency Medical Service, The North Denmark Region, Region of Southern Denmark, Region Zealand, Rigshospitalet, Denmark, The Danish Medical Research Council, The Hatter Cardiovascular Institute, London W, United Kingdom

Countries where clinical trial is conducted

Denmark,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac mortality	Cardiac mortality and hospitalisation for heart failure at one year	One year
Secondary	Myocardial infarct size	Myocardial infarct size at day 3 (72 hours area under curve serum troponin T)	72 hours
Secondary	Left ventricular function	Left ventricular function on day three and three months post pPCI (Echocardiography)	Three months
Secondary	Prognosis	Re-infarction, stroke and revascularisation at one year	One year
Secondary	Acute kidney injury	Changes in Serum Creatinine	48-72 hours