Remote Ischemic Preconditioning in Primary PCI

This study has been completed.
Sponsor:
Collaborators:
Falck, Denmark
Doctor's ambulance Services, Aarhus, Denmark
Royal Brompton & Harefield NHS Foundation Trust
The Hospital for Sick Children
Information provided by:
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00435266
First received: February 13, 2007
Last updated: February 16, 2009
Last verified: February 2009

February 13, 2007
February 16, 2009
February 2007
November 2008   (final data collection date for primary outcome measure)
Salvage index (% of left ventricle): Salvage / Area at Risk (AAR) by SPECT [ Time Frame: 30 days ] [ Designated as safety issue: No ]
Salvage index (% of left ventricle): Salvage / Area at Risk (AAR) by SPECT
Complete list of historical versions of study NCT00435266 on ClinicalTrials.gov Archive Site
  • Final infarct size. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Proportion of patients achieving ≥70% ST-resolution 90 minutes following pPCI [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
  • Proportion of patients achieving spontaneous ST-resolution before pPCI [ Time Frame: Immediate ] [ Designated as safety issue: No ]
  • Proportion of patients with increase in ST-elevation during pPCI. [ Time Frame: Immediate ] [ Designated as safety issue: No ]
  • Time from first ECG to ≥70% ST-resolution (continuous parameter) [ Time Frame: Minutes ] [ Designated as safety issue: No ]
  • Time from first wire to ≥70% ST-resolution (continuous parameter) [ Time Frame: Minutes ] [ Designated as safety issue: No ]
  • ST resolution immediately after ending the procedure (evaluated in relation to ST elevation on ECG obtained just prior to the pPCI procedure). [ Time Frame: Minutes ] [ Designated as safety issue: No ]
  • Prompt angiographic success: [ Time Frame: Immediate ] [ Designated as safety issue: No ]
  • Corrected TIMI frame count (cTFC). [ Time Frame: Minutes ] [ Designated as safety issue: No ]
  • TIMI flow measured immediately after ending the interventional procedure. [ Time Frame: Minutes ] [ Designated as safety issue: No ]
  • Myocardial blush. [ Time Frame: Minutes ] [ Designated as safety issue: No ]
  • Procedure duration. [ Time Frame: Minutes ] [ Designated as safety issue: No ]
  • Total duration of hospitalisation. [ Time Frame: Days ] [ Designated as safety issue: No ]
  • MACE after 30 days. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • TnT release - determined 90-102 hours after symptom onset. [ Time Frame: 90-102 hours ] [ Designated as safety issue: No ]
  • Echocardiographic data (acute and after 1 month): [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • WMI. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Left ventricular ejection fraction (LVEF) (%): (EDV - ESV)/EDV. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Myocardial scintigraphy data: [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Regional wall motion and regional thickening. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Technical success. [ Time Frame: Immediate ] [ Designated as safety issue: No ]
  • Final infarct size.
  • Proportion of patients achieving ≥70% ST-resolution 90 minutes following pPCI
  • Proportion of patients achieving spontaneous ST-resolution before pPCI
  • Proportion of patients with increase in ST-elevation during pPCI.
  • Time from first ECG to ≥70% ST-resolution (continuous parameter)
  • Time from first wire to ≥70% ST-resolution (continuous parameter)
  • ST resolution immediately after ending the procedure (evaluated in relation to ST elevation on ECG obtained just prior to the pPCI procedure).
  • Prompt angiographic success:
  • Corrected TIMI frame count (cTFC).
  • TIMI flow measured immediately after ending the interventional procedure.
  • Myocardial blush.
  • Procedure duration.
  • Total duration of hospitalisation.
  • MACE after 30 days.
  • TnT release – determined 90-102 hours after symptom onset.
  • Echocardiographic data (acute and after 1 month):
  • WMI.
  • Left ventricular ejection fraction (LVEF) (%): (EDV – ESV)/EDV.
  • Myocardial scintigraphy data:
  • Regional wall motion and regional thickening.
  • Technical success.
Not Provided
Not Provided
 
Remote Ischemic Preconditioning in Primary PCI
The Effect of Remote Preconditioning in Primary Percutaneous Intervention of Acute ST Elevation Myocardial Infarction

Primary percutaneous coronary intervention (pPCI) is the preferred treatment in ST elevation myocardial infarction (STEMI). The infarct-related artery (IRA) can be opened in more than 90% of the patients. However, STEMI patients still end up with a persistent perfusion defect of highly variable magnitude indicating that adjunctive treatment may add further protection against tissue damage. Ischemic preconditioning (IPC) is an intervention by which myocardium threatened by ischemia is exposed to short and repeated sublethal ischemic episodes prior to sustained ischemia (local IPC). A systemic response with protection of more remote organs (remote IPC (rIPC)) also can be induced. We have recently found that the infarct reducing effect can be obtained by obstruction of an extremity even though the remote stimulus is initiated during sustained occlusion of a coronary artery, the so-called remote preconditioning (rPerC). The clinical perspective is now to examine if rPerC can reduce the infarct size in patients with unpredictable ischemia in ST elevation myocardial infarction (STEMI). We perform a randomized study where patients en route for pPCI are allocated to either rPerC or a standard treatment to evaluate whether the tissue damage can be reduced. Effect measure will be infarct size determined by scintigraphy (final infarct size and salvage).

Primary percutaneous coronary intervention (pPCI) is the preferred treatment in ST elevation myocardial infarction (STEMI). The infarct-related artery (IRA) can be opened in more than 90% of the patients. However, STEMI patients still end up with a persistent perfusion defect of highly variable magnitude indicating that adjunctive treatment may add further protection against tissue damage. Ischemic preconditioning (IPC) is an intervention by which myocardium threatened by ischemia is exposed to short and repeated sublethal ischemic episodes prior to sustained ischemia (local IPC). A systemic response with protection of more remote organs (remote IPC (rIPC)) also can be induced. We have recently found that the infarct reducing effect can be obtained by obstruction of an extremity even though the remote stimulus is initiated after sustained occlusion of a coronary artery, the so-called remote preconditioning (rPerC). The clinical perspective is now to examine if rPerC can reduce the infarct size in patients with unpredictable ischemia in ST elevation myocardial infarction (STEMI). We perform a randomized study where patients en route for pPCI are allocated to either rPerC or a standard treatment to evaluate whether the tissue damage can be reduced. Effect measure will be infarct size determined by scintigraphy (final infarct size and salvage).

Purpose

The purpose of the present study is to examine the utility of rPerC in STEMI patients treated with pPCI. The effect will be evaluated by 1) limitation of infarct size (salvage and final infarct size) determined by myocardial scintigraphy (SPECT), 2) electrocardiographic and angiographic signs of tissue perfusion, 3) release of ischemic markers 5) echocardiographic markers of left ventricular function and 5) clinical end-points (Major Adverse Cardiac Events (MACE: death, reinfarction, need for revascularisation, invalidating stroke)) at discharge and after 30 days.

Description and evaluation of the ethical aspects of the study

Study patients treated with pPCI are randomized to pretreatment with rPerC or no pretreatment (control group). The randomization will take place in the ambulance or at the local hospital. With the aim of not causing unnecessary delays, the pretreatment is discontinued if the patient arrives at the cath. lab. before the pretreatment is completed.The discomfort in connection with the pretreatment has been shown to be minimal.

Information regarding study population

The patients are recruited among patients admitted or transferred to Department of Cardiology B, Skejby Sygehus for pPCI treatment for STEMI.

Review on the methods used

rPerC The pretreatment in the rPerC group comprises 4 x (5 min. occlusion of right upper extremity followed by 5 min. reperfusion) which is performed during the transportation towards Skejby Sygehus. The occlusion is obtained by inflation of a blood pressure tourniquet placed on the patient's right thigh to 200 mm Hg or 25 mmHg above the patient's systolic blood pressure when higher than 200 mm Hg.

Angiography The initial angiography is performed in at least two planes after administration of nitroglycerin 0.2 mg intracoronary and filmed at 25 frames/sec. The lesion should be placed centrally in the picture with the tip of the guiding catheter visual in the picture.

The final angiography is performed in the same planes as the initial angiography and after administration of nitroglycerin 0.2 mg intracoronary. The angiography is filmed at 25 frames/sec. and the filming is continued until a clear projection of sinus coronarius. The angiogram is filmed with and without magnification with the aim of projecting the periphery of the vessels.

The final angiography is performed two minutes after the last dilatation - provided that the patient is hemodynamically stable.

Percutaneous intervention and antithrombotic treatment The patients will have PCI performed in accordance with the existing procedures and guidelines at Skejby Hospital.

Electrocardiogram (ECG) and monitoring Continuous 12-lead ST-monitoring is initiated on scene by use of a commercial monitor-defibrillator (LIFEPAK 12, Medtronic Emergency Response Systems, USA), and continued during transport to the local hospital (if not bypassed) and during transfer to the interventional hospital. On arrival at the interventional hospital traditional ECG electrodes are replaced by radiolucent carbon fiber lead wire electrodes (Ambu Blue Sensor QR electrodes, Ambu A/S, Denmark) enabling ST-monitoring to be continued during and 90 minutes following PCI. The analog ECG signals sampled by the system are digitized at a sample rate of 500 Hz for processing by the GE/Marquette Medical Systems 12SL ECG interpretive algorithm. At 30-second interval the ST-monitoring program generates a median QRST-complex for all 12 leads based on a 10-second epoch of ECG data. From each of these median QRST-complexes the program estimates the ST-deviation at the STM point, halfway between the J-point of the QRS complex and the start of the T-wave. If a 0.1 mV change in ST-deviation lasts for 2.5 minutes then the software automatically acquires and stores a 10-second 12-lead ECG waveform. All 12-lead ECG waveforms and continuous ST-monitoring data are transferred to a personal computer and stored by a random key for subsequent blinded analysis at the Core Lab. at Skejby Sygehus.

Biochemical ischemia markers Circulating concentrations of troponin T (TnT) is measured at arrival, 8-12 hours, 20-24 hours and finally 90-102 hours after symptom onset.

Scintigraphic methods Two scintigraphic examinations are performed to determination of area at risk (AAR), final infarct size (FIS), regional wall motion and regional wall thickening respectively.

Area at risk (AAR): (That part of left ventricle that is without perfusion prior to PCI) Determined by tracer injection during ongoing coronary occlusion which means tracer injection prior to PCI but imaging after pPCI.

Final infarct size (FIS): (That part of left ventricle that is without perfusion 1 month after PCI) Determined by myocardial scintigraphy at rest 1 month after pPCI.

The following parameters are calculated:

Salvage : AAR minus FIS (% of left ventricle) Salvage index (%): Salvage / AAR. Left ventricular ejection fraction (LVEF) (%): (EDV - ESV)/EDV. Each myocardial scintigraphy is performed after administration of 700 ± 10% MBq 99mTc-Sestamibi as an intravenous bolus injection. Acquisition is performed as gated SPECT within 8 hours after tracer injection. The myocardial perfusion is analyzed and quantitized by the use of the interpretation software QPS and QGS. At each examination partly myocardial perfusion defect as a percentage of left ventricular myocardium, partly left ventricular end-diastolic and end-systolic volume (EDV and ESV) and partly regional wall motion and wall thickening is determined.

Design and data registration The patients are randomized to pPCI treatment with or without prior rIPC. All data analyzes from the study will be analyzed blinded regarding to the patient's randomization.

For each participant included in the study, a case record form (CRF) is filled in.

Definition and characteristic of effect parameters and other registered data A consecutive patient registration is performed by a characteristic of the study population and a registration of causes of exclusion. Clinical, angiographic and procedure related variables as in the West-Danish Heart Database will be used.

Data evaluation For each of the primary and secondary clinical effect parameters, a comparative examination of the rPerC and not rPerC treated patient groups is performed.

Statistics Dimensioning the study: Previous investigations have shown that area at risk in connection with STEMI is approximately 30% of left ventricle. Experiences from investigations at Department of Cardiology B and Department of Nuclear Medicine, Skejby Sygehus, have shown that the final infarct size in STEMI patients treated with pPCI is approximately 15%.

It is estimated that a 20% reduction in infarct size (e.g. from 15% to 12%) will be clinically relevant. With a spreading of the infarct size of 15%, which are in accordance with our previous findings, detection of such a reduction with a risk of type 2 errors of 80% (2α=0.80) will require 109 patients in each group. We plan inclusion of a total of 250 patients to secure complete data.

The study will be analyzed after intention-to-treat principles. A final specification will be performed with unpaired parametric or non parametric statistics.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Myocardial Infarction
Procedure: Remote ischemic preconditioning
Inflation of blood pressure cuff 4 x 5 minutes during transportation to primary PCI
  • Experimental: 1
    Remote ischemic preconditioning
    Intervention: Procedure: Remote ischemic preconditioning
  • No Intervention: 2
    Intervention: Procedure: Remote ischemic preconditioning

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
250
February 2009
November 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Acute chest pain or equivalent symptoms during > 30 minutes.
  2. Duration of symptoms < 12 hours.
  3. Cumulated ST elevation > 2 mm in two contiguous leads.
  4. Age ≥ 18 years.
  5. Informed consent

Exclusion Criteria:

  1. Previous by-pass surgery.
  2. Pulseless femoral artery.
  3. Left bundle branch block in ECG (LBBB).
  4. Acute MI and/or treatment with thrombolysis within 30 days.
  5. Patients treated with cooling or patients who have had cardiac arrest.
  6. Diabetic patients
  7. Patients with arteriovenous shunts for the purpose of hemodialysis
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00435266
95093546-1
No
Hans Erik Bøtker, MD. Ph.D., Professor, Aarhus University Hospital Skejby
University of Aarhus
  • Falck, Denmark
  • Doctor's ambulance Services, Aarhus, Denmark
  • Royal Brompton & Harefield NHS Foundation Trust
  • The Hospital for Sick Children
Study Director: Torsten T Nielsem, MD Department of Cardiology, Aarhus University Hospital Skejby
Principal Investigator: Hans Erik Bøtker, MD, PhD Department of Cardiology, Aarhus University Hospital Skejby
University of Aarhus
February 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP