Remote Ischaemic Conditioning in Endovascular Recanalization for Proximal Anterior Circulation Occlusion Study

NCT03152799 | Unknown Phase 1 DMC

• 1 other identifier: 222254
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Ischaemic stroke causes significant morbidity and mortality and is a leading cause of disability within an ageing United Kingdom (UK) population. Proximal anterior circulation occlusion is associated with a particularly poor prognosis, but its management has undergone a paradigm shift following clinical introduction of endovascular recanalization, establishing rapid reperfusion of the ischaemic penumbra. Remote ischaemic conditioning (RIC) is highly effective at attenuating cerebral infarction in basic research studies and has the potential to further improve patient outcome if used as an adjunct to invasive revascularisation strategies. We aim to trial remote ischaemic conditioning at the time of revascularisation, and then daily for the duration of the seven-day in-patient stay, compared to a sham conditioning procedure. This pilot, single-centre study will determine efficacy/ tolerability of RIC to reduce cerebral infarction (primary endpoint: determined by brain magnetic resonance imaging \[MRI\]) and improve functional status (secondary end-points: National Institutes of Health Stroke Severity (NIHSS); European Quality of Life questionnaire EurQoL), with the data providing the necessary parameters for power calculations and leveraging charitable funding for a subsequent multi-centre study.

Conditions

Ischemic Stroke

Keywords

remote ischaemic conditioning; remote ischemic conditioning; cerebral infarction; ischaemia reperfusion injury; ischemia reperfusion injury; anterior circulation stroke; mechanical thrombectomy

Outcome Measures

Primary Outcomes (1)

• reduction of infarct size as proportion of ischaemic penumbra following revascularisation

  Proportion of ischaemic penumbra determined by MRI at 3 months post-revascularisation

  3 months after revascularisation / thrombectomy

Secondary Outcomes (4)

• Reduction of cerebral oedema and infarct size (second-phase reperfusion injury)

  MRI at 7 days post-thrombectomy

• Neurological Recovery at 24 h and 3 months post-revascularisation

  at 24h hours and 3 months post-revascularisation

• Neurological Recovery at 24 h and 3 months post-revascularisation

  at 24h hours and 3 months post-revascularisation

• Neurological Recovery at 24 h and 3 months post-revascularisation

  at 24h hours and 3 months post-revascularisation

Study Arms (2)

Remote Ischaemic Pre-Conditioning (RIPC) Intervention

EXPERIMENTAL

Remote Ischaemic Pre-Conditioning intervention to be applied via peripheral blood pressure cuff inflation/deflations to upper lower limb contra-lateral to affected side of hemiparesis

Procedure: RIPC Remote Ischaemic Pre-Conditioning

Sham Control

SHAM COMPARATOR

Sham Control to be applied via peripheral blood pressure cuff inflation/deflations to upper lower limb contra-lateral to affected side of hemiparesis

Other: Sham Control

Interventions

RIPC Remote Ischaemic Pre-Conditioning PROCEDURE

intermittent limb ischaemia via a peripheral blood pressure cuff inflation and deflation

Also known as: Remote Ischaemic PreConditioning

Remote Ischaemic Pre-Conditioning (RIPC) Intervention

Sham Control OTHER

intermittent peripheral blood pressure cuff inflation and deflation which does not induce a protective cellular response

Sham Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute, symptomatic proximal anterior circulation occlusion
• able to commence remote ischaemic conditioning within 6h of symptom onset
• identified as candidate for endovascular intervention according to local criteria

You may not qualify if:

• Age \< 18 years
• Coagulopathy; International Normalised Ratio (INR) \>2, alteplase dose \> 90mg or 0.9mg/kg; platelet count \< 50 x 10\^9/L
• pregnancy
• BP \>= 185/110 despite therapeutic intervention
• medical illness which interferes with outcome assessments (disability from other neurological disease)
• dependent on others for activities of daily living (ADLs) prior to current stroke (mRS modified Rankin Score was 3 - 5).
• unlikely to be able to participate in study follow-up procedures (lives \> 100 miles away; no fixed abode)
• already enrolled in another clinical trial involving investigational medicinal product or device
• baseline scan demonstrating significant prior infarction in the affected Middle Cerebral Artery (MCA) territory or an infarct that exceeds \> 1/3 MCA territory

Sponsors & Collaborators

• University College, London: lead
• University College London Hospitals: collaborator
• National Hospital for Neurology and Neurosurgery (NHNN) at Queen Square: collaborator

Related Publications (9)

• Department of Health: Progress in Improving Stroke Care. In: Office NA, editor.: The Stationary Office; 2010.

  BACKGROUND

• Hippisley-Cox J, Pringle M, Ryan R. Stroke: Prevalence, Incidence and Care in General Practices 2002-2004. Final Report to the National Stroke Audit Team. In: Physicians RCo, editor. 2004.

  BACKGROUND

• Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17.

  PMID: 25517348 BACKGROUND

• Moore JM, Griessenauer CJ, Gupta R, Adeeb N, Patel AS, Ogilvy CS, Thomas AJ. Landmark papers in cerebrovascular neurosurgery 2015. Clin Neurol Neurosurg. 2016 Sep;148:22-8. doi: 10.1016/j.clineuro.2016.06.007. Epub 2016 Jun 18.

  PMID: 27366977 BACKGROUND

• Bell RM, Yellon DM. There is more to life than revascularization: therapeutic targeting of myocardial ischemia/reperfusion injury. Cardiovasc Ther. 2011 Dec;29(6):e67-79. doi: 10.1111/j.1755-5922.2010.00190.x. Epub 2010 Jul 14.

  PMID: 20645988 BACKGROUND

• Hahn CD, Manlhiot C, Schmidt MR, Nielsen TT, Redington AN. Remote ischemic per-conditioning: a novel therapy for acute stroke? Stroke. 2011 Oct;42(10):2960-2. doi: 10.1161/STROKEAHA.111.622340. Epub 2011 Aug 11.

  PMID: 21836089 BACKGROUND

• 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.

  PMID: 24203849 BACKGROUND

• Ren C, Wang P, Wang B, Li N, Li W, Zhang C, Jin K, Ji X. Limb remote ischemic per-conditioning in combination with post-conditioning reduces brain damage and promotes neuroglobin expression in the rat brain after ischemic stroke. Restor Neurol Neurosci. 2015;33(3):369-79. doi: 10.3233/RNN-140413.

  PMID: 25868435 BACKGROUND

• Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, Li G, Ren C, Luo Y, Ling F, Jia J, Hua Y, Wang X, Ding Y, Lo EH, Ji X. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012 Oct 30;79(18):1853-61. doi: 10.1212/WNL.0b013e318271f76a. Epub 2012 Oct 3.

  PMID: 23035060 BACKGROUND

Related Links

• Hatter Cardiovascular Institute

MeSH Terms

Conditions

Ischemic Stroke; Cerebral Infarction; Reperfusion Injury

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Infarction; Brain Ischemia; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Postoperative Complications

Study Officials

• Robert M Bell, PhD MRCP

  Hatter Cardiovascular Institute UCL

  PRINCIPAL INVESTIGATOR

• Derek Yellon, PhD DSc

  Hatter Cardiovascular Institute UCL

  STUDY DIRECTOR

Central Study Contacts

Richard Perry, PhD MRCP

CONTACT

020 3448 3416; richard.perry@uclh.nhs.uk

Robert Simister, PhD MRCP

CONTACT

020 3448 3416; robert.simister@uclh.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, Care Provider / Clinician Health Professional, Investigator, and Outcomes assessors will be blinded to the allocation and randomisation of study participatants. It is anticipated that
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: pilot, single-centre, double-blind, sham-controlled (non-clinical trial of investigational medicinal product \[non-CTIMP\]) study of repeated daily remote ischaemic conditioning vs placebo/sham in the context of acute anterior circulation stroke

Study Record Dates

• First Submitted: March 8, 2017
• First Posted: May 15, 2017
• Study Start: August 1, 2017
• Primary Completion: August 1, 2019
• Study Completion: December 31, 2019
• Last Updated: May 15, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share