New Acute Treatment for Stroke - The Effect of Remote PERconditioning

Sponsor

Aarhus University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00975962

Collaborator

TRYG Foundation (Other), Aase and Ejnar Danielsens Foundation (Other), Danish National Research Foundation (Other)

120

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a blinded randomized study. Randomization for treatment/not treatment with remote perconditioning takes place during transportation to the hospital. This is because the investigators' hypothesis states that remote perconditioning is neuro-protective and the effect is proportionally larger with early treatment. As the size of the effect is unknown, the investigators will use multiple magnetic resonance imaging (MRI) scans to determine the size of a potential neuro-protective effect.

The aims of this study are:

To describe method of remote perconditioning in clinical practice regarding feasibility. Pros and cons and potential limitations.
To estimate the size of the effect of remote perconditioning in combination with recombinant tissue plasminogen activator (rtPa) treatment within four and a half hours of onset of symptoms.

Condition or Disease	Intervention/Treatment	Phase
Acute Stroke	Drug: Actilyse Procedure: Thrombolysis + remote perconditioning	Phase 3

Detailed Description

Final inclusion and informed consent takes place after first MRI in patients eligible for rtPA.

Follow-up MRI after 24h and 1 month. Clinical outcome at 3 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

New Acute Treatment for Stroke - The Effect of Remote PERconditioning

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Mar 1, 2011

Actual Study Completion Date :

Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Thrombolysis + Remote perconditioning Remote perconditioning (rIPerC) undertaken in ambulance on rute to hospital in case of suspected stroke. The rIPerC consists of 4 cycles of 5 minute total occlusion of blood flow to the non-paretic arm separated by 5 minutes of reperfusion. The occlusion is secured by inflating a standard blood pressure cuff to 25 mmHg above the systolic blood pressure. Written instruction on cuff inflation and paramedic's documentation of their procedure were written in a standard report which was turned over to a study nurse upon arrival to the hospital, and filed. The investigators were hence blinded to the prehospital rIPerC.	Procedure: Thrombolysis + remote perconditioning The rIPerC consists of 4 cycles of 5 minute total occlusion of blood flow to the non-paretic arm separated by 5 minutes of reperfusion. The occlusion is secured by inflating a standard blood pressure cuff to 25 mmHg above the systolic blood pressure. Written instruction on cuff inflation and paramedic's documentation of their procedure were written in a standard report which was turned over to a study nurse upon arrival to the hospital, and filed. The investigators were hence blinded to the prehospital rIPerC.
Active Comparator: Thrombolysis Thrombolysis without pretreatment with remote perconditioning	Drug: Actilyse Actilyse according to guidelines without pretreatment with remote persconditioning

Arm

Intervention/Treatment

Experimental: Thrombolysis + Remote perconditioning

Remote perconditioning (rIPerC) undertaken in ambulance on rute to hospital in case of suspected stroke. The rIPerC consists of 4 cycles of 5 minute total occlusion of blood flow to the non-paretic arm separated by 5 minutes of reperfusion. The occlusion is secured by inflating a standard blood pressure cuff to 25 mmHg above the systolic blood pressure. Written instruction on cuff inflation and paramedic's documentation of their procedure were written in a standard report which was turned over to a study nurse upon arrival to the hospital, and filed. The investigators were hence blinded to the prehospital rIPerC.

Procedure: Thrombolysis + remote perconditioning

The rIPerC consists of 4 cycles of 5 minute total occlusion of blood flow to the non-paretic arm separated by 5 minutes of reperfusion. The occlusion is secured by inflating a standard blood pressure cuff to 25 mmHg above the systolic blood pressure. Written instruction on cuff inflation and paramedic's documentation of their procedure were written in a standard report which was turned over to a study nurse upon arrival to the hospital, and filed. The investigators were hence blinded to the prehospital rIPerC.

Active Comparator: Thrombolysis

Thrombolysis without pretreatment with remote perconditioning

Drug: Actilyse

Actilyse according to guidelines without pretreatment with remote persconditioning

Outcome Measures

Primary Outcome Measures

Salvage index (%): Difference in infarct growth (PWI-DWI) after 24 hours among patients treated with preconditioning and those not treated. [February 2012]

Secondary Outcome Measures

Final size of the infarct (T2 MRI after 1 month). Final infarct size adjusted after prognostic factors. [February 2012]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Significant ischemic stroke suspicion (NIHSS 1-24) and paresis of an extremity.
Treatment with rtPa within 4.5 hours from debut of symptoms.
Age above 18 (changed from 01.01.2010 to no upper age limit)
Independent in daily living before the acute onset of symptoms. (mrs</=2)
MR scan showing DWI lesion, consistent with acute ischemic stroke.

Exclusion Criteria:

Contraindications for iv rtPA
Onset of symptoms older than 4.5 hours
Previous diseases of the brain: Intracranial aneurisms or arteriovenous malformations. Brain surgery or hemorrhagic stroke. Former ischemic stroke within the last 3 months.
Heart diseases: Infectious endocarditis or suspicion of septic emboli, pericarditis, ventricular thrombosis, aneurisms of the heart wall or major heart failure.
Serious diseases: Cancer, AIDS, dementia, significant abuse, renal failure, liver diseases such as liver failure, cirrhosis, portal hypertension, active hepatitis.
Pregnancy
Major ischemic stroke where the patient is unconscious.(NIHSS > 25).
Symptoms suspect for migraine, Multiple sclerosis, TIA or another neurological disease than ischemic stroke.

MR scan:

Contraindications for MRI scans
Tumor cerebri, cerebral abscesses
Known hypersensitivity to Gadovist or any of its ingredients, acute or chronic severe renal impairment (GFR < 30 ml/min/1.73m2), acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period.
Caution with using Gadovist to patients with severe cardiovascular disease, and only to be used after a risk-benefit assessment.
Caution with using Gadovist in patients with low threshold for seizures.