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

NCT ID: NCT03375762

Last Updated: 2024-01-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 572 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-07
• Study Completion Date: 2024-04-01

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.

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.

Conditions

Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: QUADRUPLE

Study Groups

Usual care plus RIPerC

Usual care for stroke code patients, with or without revascularization therapies, with Remote ischemic perconditioning (RIPerC) using an electronic tourniquet.

Group Type: EXPERIMENTAL

Remote ischemic perconditioning

Intervention Type: OTHER

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

Usual care plus Sham RIPerC

Usual care for stroke code patients, with or without revascularization therapies, with Sham remote ischemic conditioning (RIPerC)

Group Type: SHAM_COMPARATOR

Sham remote perconditioning

Intervention Type: OTHER

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

Interventions

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

Intervention Type: 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

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role: collaborator

Institut de Recerca Biomèdica de Lleida

OTHER

Sponsor Role: lead

Responsible Party

Francisco Purroy

Professor. PHD. MD. Principal investigator of Neuroclinical sciences group

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Biomedical Research Institute of Lleida (IRBLleida) Institut de Recerca Biomèdica de Lleida

Lleida, , Spain

Countries

Spain

References

Hougaard KD, Hjort N, Zeidler D, Sorensen L, Norgaard A, Hansen TM, von Weitzel-Mudersbach P, Simonsen CZ, Damgaard D, Gottrup H, Svendsen K, Rasmussen PV, Ribe LR, Mikkelsen IK, Nagenthiraja K, Cho TH, Redington AN, Botker HE, Ostergaard L, Mouridsen K, Andersen G. Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial. Stroke. 2014 Jan;45(1):159-67. doi: 10.1161/STROKEAHA.113.001346. Epub 2013 Nov 7.

Reference Type: BACKGROUND

PMID: 24203849 (View on PubMed)

England TJ, Hedstrom A, O'Sullivan S, Donnelly R, Barrett DA, Sarmad S, Sprigg N, Bath PM. RECAST (Remote Ischemic Conditioning After Stroke Trial): A Pilot Randomized Placebo Controlled Phase II Trial in Acute Ischemic Stroke. Stroke. 2017 May;48(5):1412-1415. doi: 10.1161/STROKEAHA.116.016429. Epub 2017 Mar 6.

Reference Type: BACKGROUND

PMID: 28265014 (View on PubMed)

Heusch G, Botker HE, Przyklenk K, Redington A, Yellon D. Remote ischemic conditioning. J Am Coll Cardiol. 2015 Jan 20;65(2):177-95. doi: 10.1016/j.jacc.2014.10.031.

Reference Type: BACKGROUND

PMID: 25593060 (View on PubMed)

Hess DC, Blauenfeldt RA, Andersen G, Hougaard KD, Hoda MN, Ding Y, Ji X. Remote ischaemic conditioning-a new paradigm of self-protection in the brain. Nat Rev Neurol. 2015 Dec;11(12):698-710. doi: 10.1038/nrneurol.2015.223. Epub 2015 Nov 20.

Reference Type: BACKGROUND

PMID: 26585977 (View on PubMed)

Pan J, Li X, Peng Y. Remote ischemic conditioning for acute ischemic stroke: dawn in the darkness. Rev Neurosci. 2016 Jul 1;27(5):501-10. doi: 10.1515/revneuro-2015-0043.

Reference Type: BACKGROUND

PMID: 26812782 (View on PubMed)

Purroy F, Arque G, Jimenez-Fabrega X, Subirats T, Ropero JR, Vicente-Pascual M, Cardona P, Gomez-Choco M, Pagola J, Abilleira S, Rovira A, Cirer-Sastre R, Mauri-Capdevila G; REMOTE-CAT Trial Investigators. Prehospital application of remote ischaemic perconditioning in acute ischaemic stroke patients in Catalonia: the REMOTE-CAT clinical trial. EClinicalMedicine. 2025 Apr 25;83:103208. doi: 10.1016/j.eclinm.2025.103208. eCollection 2025 May.

Reference Type: DERIVED

PMID: 40337071 (View on PubMed)

Purroy F, Arque G, Mauri G, Garcia-Vazquez C, Vicente-Pascual M, Pereira C, Vazquez-Justes D, Torres-Querol C, Vena A, Abilleira S, Cardona P, Forne C, Jimenez-Fabrega X, Pagola J, Portero-Otin M, Rodriguez-Campello A, Rovira A, Marti-Fabregas J. REMOTE Ischemic Perconditioning Among Acute Ischemic Stroke Patients in Catalonia: REMOTE-CAT PROJECT. Front Neurol. 2020 Sep 25;11:569696. doi: 10.3389/fneur.2020.569696. eCollection 2020.

Reference Type: DERIVED

PMID: 33101178 (View on PubMed)

Other Identifiers

CEIC-1744

Identifier Type: -

Identifier Source: org_study_id