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REMOTE Ischemic Perconditioning Among Acute Ischemic Stroke Patients ( REMOTE-CAT) (REMOTE-CAT)

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ClinicalTrials.gov Identifier: NCT03375762
Recruitment Status : Not yet recruiting
First Posted : December 18, 2017
Last Update Posted : December 19, 2017
Sponsor:
Collaborator:
Instituto de Salud Carlos III
Information provided by (Responsible Party):
Francisco Purroy, Institut de Recerca Biomèdica de Lleida

Brief Summary:
Stroke is one of the leading causes of death worldwide and the main cause of incapacity. Currently, the only therapies for acute ischemic stroke (AIS) patients are the administration of recombinant tissue plasminogen activator (rt-PA) and/or endovascular treatment. Unfortunately, many patients cannot benefit from these therapies due to contraindications or evolution time. Neuroprotective therapies could not only increase the benefits of available reperfusion therapies but also provide an option for patients who are not candidates for these treatments. Remote ischemic conditioning, consisting on brief episodes of transient limb ischemia, represents a new paradigm in neuroprotection. It can be categorized in pre-, per- or postconditioning, depending on the moment of application. According to studies in coronary ischemia, remote ischemic perconditioning (RIPerC) during the ischemic event is safe, cost-effective, feasible and associated with a reduction in myocardial injury. The investigators aim to conduct a multicentre study (5 university hospitals) of pre-hospital RIPerC in AIS patients (within 8 hours of stroke onset), which would include 572 stroke code activated patients (286 would undergo RIPerC and 286 would be sham). Our hypothesis is that RIPerC would be safe and would induce endogenous neuroprotective phenomena associated with good outcomes in AIS patients whether treated with revascularization therapies or not. Moreover, the development of systemic ischemic tolerance should provide metabolomic and lipidomic signatures that would present an opportunity to find specific molecular markers (biomarkers). The main objectives will be to assess: 1) RIPerC clinical benefits in AIS, 2) whether RIPerC is safe not only in AIS but also in all cases of stroke code activation, 3) whether RIPerC is associated with a reduction in cerebral infarct size and 4) metabolomic and lipidomic signatures of the RIPerC effect.

Condition or disease Intervention/treatment Phase
Ischemic Stroke Other: Remote ischemic perconditioning Other: Sham remote perconditioning Not Applicable

Detailed Description:

Stroke is one of the leading causes of death worldwide and the main cause of incapacity. Currently, the only therapies for acute ischemic stroke (AIS) patients are the administration of rt-PA and/or endovascular treatment. Unfortunately, many patients cannot benefit from these therapies due to contraindications or evolution time. Neuroprotective therapies could not only increase the benefits of available reperfusion therapies but also provide an option for patients who are not candidates for these treatments. However, most neuroprotection trials have so far failed to demonstrate their efficacy in acute phase stroke patients, despite good results in animal studies. Remote ischemic perconditioning (RIPerC) represents a new paradigm in neuroprotection. It upregulates endogenous defense systems to achieve ischemic tolerance in brain ischemia. It consists of brief episodes of transient limb ischemia. According to studies in coronary ischemia, RIPerC during the ischemic event is safe, feasible and related to reduction in myocardial injury. However, there is only limited data about the clinical utility of RIC in AIS patients. Only one small single-centre, randomized, open label clinical trial has been conducted to test RIPerC in AIS patients as an adjunctive therapy intravenous alteplase in the prehospital setting.

The investigators want to conduct a multicenter study (involving 5 university hospitals) of prehospital RIPerC in AIS patients (within 8 hours of stroke onset) in which 572 stroke code activated patients will be included (286 subjects will undergo RIPerC and 286 subjects will be sham). RIPerC will consist of five cycles of electronic tourniquet inflation during five minutes and deflation during five minutes. The main endpoint will be a good clinical outcome measured by the modified Rankin score. The investigators will also establish a secondary neuroimaging endpoint defined by the infarct size observed in a Magnetic resonance imaging performed at three days. In addition, the investigators will conduct a substudy of biomarkers in 100 patients.

Our hypothesis is that RIPerC will be safe and will induce endogenous neuroprotective phenomenon responsible for good outcome in AIS patients whether treated with revascularization therapies or not. Moreover, the development of systemic ischemic tolerance will provide a metabolomic and lipidomic signature that will offer the opportunity to find specific molecular markers (biomarkers).

Project Objectives:

  • To assess RIPerC clinical benefit in AIS measured by the modified Rankin Scale (mRS) score <3.
  • To evaluate whether RIPerC is safe not only in AIS but also in all cases of stroke code activation.
  • To assess whether RIPerC is associated with a reduction of cerebral infarct size.
  • To identify the metabolomic and lipidomic signatures of the RIPerC effect.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 572 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Health Services Research
Official Title: REMOTE Ischemic Perconditioning Among Acute Ischemic Stroke Patients in CATalonia: REMOTE-CAT PROJECT
Estimated Study Start Date : June 1, 2018
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : October 1, 2021

Arm Intervention/treatment
Experimental: Usual care plus RIPerC
Usual care for stroke code patients, with or without revascularization therapies, with Remote ischemic perconditioning (RIPerC) using an electronic tourniquet.
Other: Remote ischemic perconditioning
Five 5-minute inflations/deflations of an automatic device placed on the upper non-paretic arm initiated in the ambulance on the way to hospital in the case of stroke code activation and RACE score >0 and RACE motor item>0

Sham Comparator: Usual care plus Sham RIPerC
Usual care for stroke code patients, with or without revascularization therapies, with Sham remote ischemic conditioning (RIPerC)
Other: Sham remote perconditioning
Sham five 5-minute inflations/deflations of an automatic device placed on the upper non-paretic arm initiated in the ambulance on the way to hospital in the case of stroke code activation and RACE score >0 and RACE motor item>0




Primary Outcome Measures :
  1. Dependency [ Time Frame: Day 90±7 ]
    Modified Rankin Scale (MRS) <3. The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels: 0 (no symptom) to 5 (severe disability) and 6 (death).


Secondary Outcome Measures :
  1. Early neurological improvement rate [ Time Frame: Day 1, day 5±1 ]
    NIHSS decrease >=4 with respect to baseline

  2. Treatment Related Serious Adverse Event Rates [ Time Frame: Day 1, day 5±1, day 90±7 ]
    Number of participants with a serious adverse event related to treatment

  3. Size of the infarct volume [ Time Frame: Day 5±1 ]
    The infarct volume will be defined as the hyperintense area on the initial isotropic DWI acquired with a b value of 1000 sec/mm2

  4. Symptomatic intracranial hemorrhage [ Time Frame: 24-36 hours ]
    Symptomatic intracerebral hemorrhage (SICH) defined by the Safe Implementation of Thrombolysis in Stroke Monitoring Study protocol

  5. Omic's response [ Time Frame: Day 1, day 3, day 5±1 ]
    Metabolomic and lipidomic analyses to define a panel of serum biomarkers accurately related to Remote ischemic conditioning phenomenon.

  6. Early dependency [ Time Frame: Day 5±1, ]
    Modified Rankin Scale <3. The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels: 0 (no symptom) to 5 (severe disability) and 6 (death).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age above 18 years old
  • Suspected clinical stroke with 8 hours since onset of neurological symptoms
  • Stroke code (SC) activation
  • Independent in daily life before the onset of acute symptoms. (mrs</=2)
  • Rapid arterial occlusion evaluation (RACE) scale score>0 and RACE motor item>0
  • Written informed consent (patient or representative)

Exclusion Criteria:

  • Unknown onset of symptoms
  • Coma (GCS< 8)
  • Malignancy or significant co-morbidity thought to limit life expectancy to <6 months
  • Pregnancy
  • Taking part in another interventional study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03375762


Locations
Spain
Biomedical Research Institute of Lleida (IRBLleida) Institut de Recerca Biomèdica de Lleida Not yet recruiting
Lleida, Spain, 25198
Contact: Francisco Purroy, PhD    34973705236    fpurroy.lleida.ics@gencat.cat   
Contact: Ikram Benabdelhak, NR    34973248100 ext 2386    ibenabdelhak@irblleida.cat   
Sponsors and Collaborators
Institut de Recerca Biomèdica de Lleida
Instituto de Salud Carlos III

Publications:
Responsible Party: Francisco Purroy, Professor. PHD. MD. Principal investigator of Neuroclinical sciences group, Institut de Recerca Biomèdica de Lleida
ClinicalTrials.gov Identifier: NCT03375762     History of Changes
Other Study ID Numbers: CEIC-1744
First Posted: December 18, 2017    Key Record Dates
Last Update Posted: December 19, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Stroke
Ischemia
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia