Remote Ischaemic Conditioning After Stroke Trial (ReCAST-2) (ReCAST-2)

Remote Ischaemic Conditioning After Stroke Trial (ReCAST-2): A Pilot Randomised Controlled Phase II Trial Evaluating Remote Ischaemic Conditioning (RIC) After Hyperacute Stroke 2

Stroke has an enormous impact on both individual and society. Novel treatments are required to relieve this burden and remote ischaemic conditioning (RIC) is one such approach. RIC refers to applying non-lethal ischaemia to an area distant from an organ you are trying to protect (e.g. the brain). Pre-clinical animal stroke studies have shown RIC to be neuroprotective and help restore functional outcome when compared to control. These outcomes are achieved simply by transiently occluding the blood supply to a limb (e.g. the arm) very soon after the stroke occurs. The mechanisms of protection are unclear but may be due enhancing the body's ability to protect itself from further injury by favorably altering cerebral blood flow or reducing the detrimental effects of oxygen free radicals. Ischaemic conditioning (IC) is an intervention already applied during cardiac surgery to protect the heart from damage and it may be effective after an acute myocardial infarction. The investigators therefore plan to conduct a pilot randomised controlled trial assessing the feasibility of applying RIC (4 cycles of blood pressure cuff inflation for 5 minutes) in patients within 6 hours of ischaemic stroke. The primary outcome is feasibility of RIC. Secondary outcomes include tolerability, safety and clinical efficacy. The results will inform the design of future trials of a potential intervention is that is pragmatic, non-invasive and simple to administer.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Procedure: Remote ischaemic conditioning; Procedure: Sham

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Derbyshire
    • Derby, Derbyshire, United Kingdom, DE22 3DT
      • Derby Teaching Hospitals Foundation Trust
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Nottingham University Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Suspected clinical stroke with 6 hours of onset of neurological symptoms;
2. Age >18;
3. Written or witnessed oral consent, or relative/consultee advice.

Exclusion Criteria:

1. Pre-morbid dependency mRS>3;
2. Dementia;
3. Coma (GCS< 8);
4. Malignancy or significant co-morbidity thought to limit life expectancy to <6 months;
5. Blood sugar < 3.5 mmol/L;
6. Taking part in another clinical trial of an investigational medicinal product (CTIMP);
7. Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Remote Ischaemic Conditioning; Remote ischaemic conditioning (RIC group): 4 cycles of intermittent limb ischaemia - alternating 5 minutes inflation (20mmHg above systolic BP) followed by 5 minutes deflation of a standard upper arm blood pressure cuff	Procedure: Remote ischaemic conditioning; 1 dose (=4 cycles) of intermittent upper limb ischaemia (1 cycle = 5minutes inflation to 20mmHg above systolic BP, 5 minutes deflation). Dose escalation: (i) Recruits 1-20 receive this cycle once (ii) Recruits 21-40 receive a second dose of 4-cycles one hour after the first. (iii) Recruits 41-60 receive further dosing, twice daily until day 4.
Sham Comparator: Control; Control: 4 cycles of alternating 5 minutes inflation (up to 30 mmHg) followed by 5 minutes deflation of a standard upper arm blood pressure cuff	Procedure: Sham; 4 cycles of intermittent sham procedure (1 cycle = 5 minutes inflation to 30 mmHg, 5 minutes deflation), matching the dose escalation described in the intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trial feasibility	Recruitment feasibility (recruitment rate)	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular Event Rate [Safety and Tolerability]	Number of participants with a vascular event (including limb ischaemia, recurrent stroke, myocardial infarction, venous thrombo-embolism)	Day 1, Day 4±1, day 90±7
Treatment Related Serious Adverse Event Rates [Safety and Tolerability]	Number of participants with a serious adverse event related to treatment	Day 1, Day 4±1, day 90±7
Biomarkers	Plasma S100-beta protein	Immediately before RIC/sham at baseline; immediately after RIC/sham on Day 1; day 4±1
Biomarkers	Plasma heat-shock proteins	Immediately before RIC/sham at baseline; immediately after RIC/sham on Day 1; day 4±1
Biomarkers	Plasma cytokines	Immediately before RIC/sham at baseline; immediately after RIC/sham on Day 1; day 4±1
Impairment	National Institutes of Health Stroke Scale	Day 4±1, day 90±7
Dependency	Modified Rankin scale	Day 90±7
Disability	Barthel Index	Day 90±7
Mood	Zung depression scale	Day 90±7
Telephone cognition	Modified Telephone Interview for Cognitive Status (TICS-M)	Day 90±7

Collaborators and Investigators

• Sponsor: University of Nottingham

Publications and helpful links

General Publications

• England TJ, Hedstrom A, O'Sullivan SE, Woodhouse L, Jackson B, Sprigg N, Bath PM. Remote Ischemic Conditioning After Stroke Trial 2: A Phase IIb Randomized Controlled Trial in Hyperacute Stroke. J Am Heart Assoc. 2019 Dec 3;8(23):e013572. doi: 10.1161/JAHA.119.013572. Epub 2019 Nov 21.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): July 23, 2018
• Study Completion (Actual): July 23, 2018

Study Registration Dates

• First Submitted: January 22, 2016
• First Submitted That Met QC Criteria: May 18, 2016
• First Posted (Estimate): May 20, 2016

Study Record Updates

• Last Update Posted (Actual): October 11, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Remote ischaemic conditioning
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 16007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED