Remote Ischemic Conditioning in Patients With Acute Stroke (RESIST)

NCT03481777 | Completed Results DMC

• 1 other identifier: 2017114177
• Study Type: interventional
• Target: 1,500
• Locations: 1 country
• Sites: 4

Brief Summary

Our primary aim is to investigate whether remote ischemic conditioning (RIC) as an adjunctive treatment can improve long-term recovery in acute stroke patients as an adjunct to standard treatment.

Conditions

Stroke, Acute; Ischemic Stroke; Hemorrhagic Stroke; Intracerebral Hemorrhage; Cerebrovascular Disorders; Central Nervous System Diseases

Keywords

Remote Ischemic Conditioning; Neuroprotection

Outcome Measures

Primary Outcomes (1)

• Modified Rankin Scale at 3 Months in Acute Stroke (AIS and ICH)

  Clinical outcome (modified Rankin Scale) at 3 months in acute stroke patients (target diagnosis) (generalized ordinal logistic regression). The assessment will performed by two independent telephone or face-to-face assessors. the mRS range from 0 to 6, with higher scores representing worse outcome (mRS 0, no symptoms; mRS 6, death) If disagreement occurs the patient will be contacted by a third assessor (face-to-face or telephone) who is blinded to the intervention who will assess the level of dependency. * If disagreement occurs between two telephone assessments - a third, and final, telephone or face-to-face assessment will be made. * If disagreement occurs between one face-to-face assessment and one telephone assessment * the face-to-face will be considered the final assessment * If disagreement occurs between two face-to-face assessments - a third, and final, telephone or face-to-face assessment will be made.

  3 months

Secondary Outcomes (11)

• Difference Neurological Impairment During the First 24 Hours

  24 hours

• Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Acute Ischemic Stroke

  3 months

• Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Acute Ischemic Stroke Receiving Reperfusion Therapy

  3 months

• Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Patients With Intracerebral Hemorrhage (ICH)

  3 months

• Difference in Proportion of Patients With Complete Remission of Symptoms Within 24 Hours (TIA; Both With and Without DWI)

  3 months

Other Outcomes (11)

• Clinical Outcome [Modified Rankin Scale (mRS) at 3 Months in Ischemic Stroke Patients and the Extended Remote Ischemic Postconditioning Protocol (Substudy at Aarhus University Hospital]

  3 months

• Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Intracerebral Hemorrhage Patients and the Extended Remote Ischemic Postconditioning Protocol (Substudy at Aarhus University Hospital)

  3 months

• Endovascular Treatment(EVT) -Eligibility (MRI Assessed) in RIC Treated AIS Patients With Large Vessel (Substudy at Aarhus University Hospital)

  6 hours

Study Arms (2)

Remote Ischemic Conditioning

ACTIVE COMPARATOR

Remote ischemic conditioning (RIC) is applied in the hyperacute prehospital phase using an automated RIC device. Treatment characteristics: Five cycles (50 minutes), each consisting of five minutes of cuff inflation followed by five minutes with a deflated cuff. The cuff pressure will be 200 mmHg; but if initial systolic blood pressure is above 175 mmHg, the cuff is automatically inflated to 35 mmHg above the systolic blood pressure. * Initial remote ischemic conditioning: prehospital phase, all included patients * Remote ischemic conditioning at +6 hours: In-hospital, only patients with AIS and ICH, all centres * Remote Ischemic Postconditioning (twice daily for 7 days): In-hospital/rehabilitation, Only patients with AIS and ICH and only at Aarhus University Hospital Usual care with or without acute reperfusion therapy

Device: Remote Ischemic Conditioning

Sham - Remote Ischemic Conditioning

SHAM COMPARATOR

Sham remote ischemic conditioning (Sham-RIC) is applied in the hyperacute prehospital phase using an automated Sham-RIC device. Treatment characteristics: Five cycles (50 minutes), each consisting of five minutes of cuff inflation followed by five minutes with a deflated cuff. The cuff pressure will be always be 20 mmHg. * Initial Sham remote ischemic conditioning: prehospital phase, all included patients * Sham Remote ischemic conditioning at +6 hours: In-hospital, only patients with AIS and ICH, all centres * Sham Remote Ischemic Postconditioning (twice daily for 7 days): In-hospital/rehabilitation, Only patients with AIS and ICH and only at Aarhus University Hospital Usual care with or without acute reperfusion therapy.

Device: Sham Remote Ischemic Conditioning

Interventions

Remote Ischemic Conditioning DEVICE

RIC is commonly achieved by inflation of a blood pressure cuff to induce 5-minute cycles of limb ischemia alternating with 5 minutes of reperfusion.

Remote Ischemic Conditioning

Sham Remote Ischemic Conditioning DEVICE

Sham Comparator (Sham-RIC)

Sham - Remote Ischemic Conditioning

Eligibility Criteria

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

You may qualify if:

• Male and female patients (≥ 18 years)
• Prehospital putative stroke (Prehospital Stroke Score, PreSS \>= 1)
• Onset of stroke symptoms \< 4 hours before RIC/Sham-RIC
• Independent in daily living before symptom onset (mRS ≤ 2)

You may not qualify if:

• Intracranial aneurisms, intracranial arteriovenous malformation, cerebral neoplasm or abscess
• Pregnancy
• Severe peripheral arterial disease in the upper extremities
• Concomitant acute life-threatening medical or surgical condition
• Arteriovenous fistula in the arm selected for RIC

Sponsors & Collaborators

• Grethe Andersen: lead
• Danish National Research Foundation: collaborator
• Central Denmark Region: collaborator

Study Sites (4)

Department of Neurology Aarhus University Hospital

Aarhus, Danmark, DK-8000, Denmark

Location

Aalborg University Hospital

Aalborg, DK, 9000, Denmark

Location

Odense University Hospital

Odense, DK, 5000, Denmark

Location

Department of Neurology Regional Hospital West Jutland

Holstebro, DK-7500, Denmark

Location

Related Publications (9)

• 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.

  PMID: 26585977 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

• Blauenfeldt RA, Hjort N, Gude MF, Behrndtz AB, Fisher M, Valentin JB, Kirkegaard H, Johnsen SP, Hess DC, Andersen G. A multicentre, randomised, sham-controlled trial on REmote iSchemic conditioning In patients with acute STroke (RESIST) - Rationale and study design. Eur Stroke J. 2020 Mar;5(1):94-101. doi: 10.1177/2396987319884408. Epub 2019 Oct 25.

  PMID: 32232175 BACKGROUND

• Blauenfeldt RA, Hjort N, Valentin JB, Homburg AM, Modrau B, Sandal BF, Gude MF, Hougaard KD, Damgaard D, Poulsen M, Diedrichsen T, Schmitz ML, von Weitzel-Mudersbach P, Christensen AA, Figlewski K, Grove EL, Hreietharsdottir MK, Lassesen HM, Wittrock D, Mikkelsen S, Vaeggemose U, Juelsgaard P, Kirkegaard H, Rostgaard-Knudsen M, Degn N, Vestergaard SB, Damsbo AG, Iversen AB, Mortensen JK, Petersson J, Christensen T, Behrndtz AB, Botker HE, Gaist D, Fisher M, Hess DC, Johnsen SP, Simonsen CZ, Andersen G. Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial. JAMA. 2023 Oct 3;330(13):1236-1246. doi: 10.1001/jama.2023.16893.

  PMID: 37787796 RESULT

• Blauenfeldt RA, Simonsen CZ, Valentin JB, Johnsen SP, Hjort N, Andersen G. Outcomes Following Adherence to a Randomized Stroke Trial Protocol. JAMA Netw Open. 2024 Jan 2;7(1):e2349730. doi: 10.1001/jamanetworkopen.2023.49730.

  PMID: 38165678 RESULT

• Blauenfeldt RA, Mortensen JK, Hjort N, Valentin JB, Homburg AM, Modrau B, Sandal BF, Gude MF, Berhndtz AB, Johnsen SP, Hess DC, Simonsen CZ, Andersen G. Effect of Remote Ischemic Conditioning in Ischemic Stroke Subtypes: A Post Hoc Subgroup Analysis From the RESIST Trial. Stroke. 2024 Apr;55(4):874-879. doi: 10.1161/STROKEAHA.123.046144. Epub 2024 Feb 1.

  PMID: 38299363 RESULT

• Ganesh A, Gaist D, Modrau B, Gude MF, Behrndtz AB, Andersen G, Simonsen CZ, Blauenfeldt RA. Pre-hospital treatment duration and efficacy of remote ischaemic conditioning in the RESIST randomised-controlled trial. Eur Stroke J. 2026 Jan 1;11(1):aakaf015. doi: 10.1093/esj/aakaf015.

  PMID: 41614496 DERIVED

• Blauenfeldt RA, Hess DC, Gaist D, Modrau B, Valentin JB, Johnsen SP, Hjort N, Behrndtz AB, Gude MF, Zhao W, Jensen J, Andersen G, Simonsen CZ. The Effect of Remote Ischemic Conditioning in Patients Treated with Endovascular Therapy: A RESIST Trial Post Hoc Study. Transl Stroke Res. 2025 Dec;16(6):2173-2184. doi: 10.1007/s12975-025-01379-5. Epub 2025 Sep 6.

  PMID: 40913213 DERIVED

• Blauenfeldt RA, Waller J, Drasbek KR, Bech JN, Hvas AM, Larsen JB, Andersen MN, Nielsen MC, Kjolhede M, Kjeldsen M, Gude MF, Khan MB, Baban B, Andersen G, Hess DC. Effect of Remote Ischemic Conditioning on the Form and Function of Red Blood Cells in Patients With Acute Ischemic Stroke. Stroke. 2025 Mar;56(3):603-612. doi: 10.1161/STROKEAHA.124.048976. Epub 2025 Jan 30.

  PMID: 39882626 DERIVED

MeSH Terms

Conditions

Stroke; Ischemic Stroke; Hemorrhagic Stroke; Cerebral Hemorrhage; Cerebrovascular Disorders; Central Nervous System Diseases

Condition Hierarchy (Ancestors)

Brain Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Intracranial Hemorrhages; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Rolf Blauenfeldt
• Organization: Aarhus University Hospital

rolfblau@rm.dk

0045 78450000

Study Officials

• Grethe Andersen, MD, DMSc

  Aarhus University Hospital, Department of Neurology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participant. Outcome assessor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, DMSc, Senior Consultant, MD

Model Details: Prospective, randomized, patient-assessor blinded, sham-controlled trial

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: March 29, 2018
• Study Start: March 15, 2018
• Primary Completion: February 3, 2023
• Study Completion: February 3, 2023
• Last Updated: January 27, 2025
• Results First Posted: January 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following arcticle publication
• Access Criteria: Proprosals should be directed to rolfblau@rm.dk. To gain access data requestors will need to sign a data processing agreement.

Locations

DK (4)