Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Danish National Research Foundation | OTHER |
| Central Denmark Region | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
Stroke is the second-leading cause of death worldwide and a leading cause of serious, long-term disability. The most common type is acute ischemic stroke (AIS) which occurs in 85% of cases. Acute cerebral thromboembolism leads to an area of permanent damage (infarct core) in the most severely hypoperfused area and a surrounding area of impaired, yet salvageable tissue known as the "ischemic penumbra".
Intravenous alteplase (IV tPA) and endovascular treatment (EVT) are approved acute reperfusion treatments of AIS to be started within the first 4½-6 hours (in some up to 24 hours) and as soon as possible after symptom onset to prevent the evolution of the infarct core. However, reperfusion itself may paradoxically result in tissue damage (reperfusion injury) and may contribute to infarct growth. Infarct progression can continue for days following a stroke, and failure of the collateral flow is a critical factor determining infarct growth.
On the other hand, in intracerebral hemorrhage (ICH) the culprit is an eruption of blood into the brain parenchyma causing tissue destruction with a massive effect on adjacent brain tissues. Hematoma expansion as well as inflammatory pathways that are activated lead to further tissue damage, edema, and penumbral hypoperfusion. The prognosis after ICH is poor with a one-month mortality of 40%.
Novel therapeutics and neuroprotective strategies that can be started ultra-early after symptom onset are urgently needed to reduce disability in both AIS and ICH.
Ischemic conditioning is one of the most potent activators of endogenous protection against ischemia-reperfusion injury. Remote Ischemic Conditioning (RIC) can be applied as repeated short-lasting ischemia in a distant tissue that results in protection against subsequent long-lasting ischemic injury in the target organ. This protection can be applied prior to or during a prolonged ischemic event as remote ischemic pre-conditioning (RIPreC) and per-conditioning (RIPerC), respectively, or immediate after reperfusion as remote ischemic post-conditioning (RIPostC). 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.
Preclinical studies show that RIC induces a promising infarct reduction in an experimental stroke model. Results from a recent proof-of-concept study at our institution indicate that RIPerC applied during ambulance transportation as an adjunctive to in-hospital IV tPA increases brain tissue survival after one month. Furthermore, RIPerC patients had less severe neurological symptoms at admission and tended to have decreased perfusion deficits.
To-date, no serious adverse events have been documented in RIC.
RIC is a non-pharmacologic and non-invasive treatment without noticeable discomfort that has first-aid potential worldwide. However, whether combined remote ischemic per- and postconditioning can improve long-term recovery in AIS and ICH has never been investigated in a randomized controlled trial.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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.
Usual care with or without acute reperfusion therapy |
|
| 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.
Usual care with or without acute reperfusion therapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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.
| 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Difference Neurological Impairment During the First 24 Hours | Neurological deficits are documented using Prehospital Stroke Score (PreSS). Prehospital Stroke Score is assessed in the the ambulance and at 24-hour or at discharge (if discharge occurs before 24 hours). The PreSS score consists of the Cincinnati Prehospital Stroke Scale (CPSS) with an additional opportunity to report other neurological symptoms (e.g. ataxia, sensory disturbances and visual field loss), and PASS (Prehospital Acute Stroke Severity Scale). The PreSS score range from 0-6, with 6 representing the most severe neurological deficits. |
| Measure | Description | Time Frame |
|---|---|---|
| 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] | Clinical outcome [modified Rankin Scale (mRS) at 3 months in ischemic stroke patients and the extended remote ischemic postconditioning protocol Ordinal logistic regression analysis will be performed.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.](streamdown:incomplete-link) |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Grethe Andersen, MD, DMSc | Aarhus University Hospital, Department of Neurology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Neurology Aarhus University Hospital | Aarhus | Danmark | DK-8000 | Denmark | ||
| Aalborg University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26585977 | Background | 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. | |
| 24203849 | 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. |
Not provided
Not provided
Individual participant data that underlie the results reported in this article after deidentification
Beginning 3 months and ending 5 years following arcticle publication
Proprosals should be directed to rolfblau@rm.dk. To gain access data requestors will need to sign a data processing agreement.
Not provided
The RESIST trial is a prehospital stroke trial. Patients are randomzied to remote ischemic conditioning or sham in the ambualnce before their final diagnosis. Patients who have a stroke (ischemic stroke or intracerebral hemorrhage, n= 902) are the target population and treated further according to randomization and outcome assessed as 3 months modified Rankin Scale . Patients with a non stroke diagnosis (n=531) are not treated further and not followed beyond hospital discharge.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Remote Ischemic Condtioning (RIC) | Patients with a prehospital stroke suspicion were randomized and treated with either RIC or sham RIC in the ambulance and continued at the stroke center. Patients with a in-hospital diagnosis of acute ischemic stroke or intracerebral hemorrhage were the target group and study population for the primary endpoint (modified Intention to Treat) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 29, 2018 |
Not provided
Prospective, randomized, patient-assessor blinded, sham-controlled trial
Not provided
Not provided
Participant. Outcome assessor.
| Sham Remote Ischemic Conditioning | Device | Sham Comparator (Sham-RIC) |
|
| 24 hours |
| Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Acute Ischemic Stroke | Clinical outcome (modified Rankin Scale) at 3 months in acute stroke patients (target diagnosis) (generalized ordinal logistic regression). TThe 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 |
| Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Acute Ischemic Stroke Receiving Reperfusion Therapy | Clinical outcome (modified Rankin Scale) at 3 months inacute ischemic stroke receiving reperfusion therapy (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 |
| Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Patients With Intracerebral Hemorrhage (ICH) | Clinical outcome (modified Rankin Scale) at 3 months in patients with intracerebral hemorrhage (ICH) (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 |
| Difference in Proportion of Patients With Complete Remission of Symptoms Within 24 Hours (TIA; Both With and Without DWI) | Difference in proportion of patients with complete remission of symptoms within 24 hours (TIA; both with and without DWI) Diagnosis of TIA is documented in the electronic case report form | 3 months |
| Major Adverse Cardiac and Cerebral Events (MACCE) | MACCE is defined as: Cardiovascular events (cardiovascular death, myocardial infarction, acute ischemic or hemorrhagic stroke) Cardiovascular death: Death from known cardiovascular cause or sudden death from unknown cause (no identified cause of death in medical history and/or autopsy) Acute myocardial infarction: Admission with a discharge diagnosis of ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP) Stroke: Admission with a discharge diagnosis of acute ischemic or hemorrhagic stroke. Evaluation is performed using the Danish National Patient Register (LPR) and the DSR at two time points (6 and 15 months after the inclusion of the last patient). Diagnosis of AIS/TIA, ICH and MI (STEMI, NSTEMI, and UAP) are made according to national clinical practice guidelines. | 3 months |
| Early Neurological Improvement in Acute Ischemic Stroke Patients (AIS) | Reduction in National Institute of Health Stroke Scale (NIHSS) ≥ 4 (baseline versus 24-Hour NIHSS). NIHSS range from 0 to 42, with higher scores representing worse neurological function. | 24 hours |
| Early Neurological Improvement in Patients With Intracerebral Hemorrhage (ICH) | Reduction in National Institute of Health Stroke Scale (NIHSS) ≥ 4 (baseline versus 24-Hour NIHSS). NIHSS range from 0 to 42, with higher scores representing worse neurological function. | 24 hours |
| Quality of Life Measures at 3 Months in AIS and ICH Patients | Quality of life (WHO-5 Well-Being Index) measures in AIS and ICH patients at 3 months | 3 months |
| Bed-day Use in AIS and ICH Patients | Bed-day use, measured at 3 months, in AIS and ICH patients | 3 months |
| Three-month and One-year Mortality | All-cause mortality is assessed and subdivided into cardiovascular mortality versus non-cardiovascular mortality | 3 and 12 months |
| 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) | Clinical outcome (modified Rankin Scale (mRS) at 3 months in intracerebral hemorrhage patients and the extended remote ischemic postconditioning protocol 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 |
| Endovascular Treatment(EVT) -Eligibility (MRI Assessed) in RIC Treated AIS Patients With Large Vessel (Substudy at Aarhus University Hospital) | Proportion of RIC treated AIS patients with large vessel occlusion (LVO) eligible to EVT treatment compared to standard treatment, adjusted for prehospital stroke severity (PreSS) and symptom duration
| 6 hours |
| Infarct Growth in AIS Patients (Substudy at Aarhus University Hospital) | 24-hour infarct growth on DWI-MRI (Difference in lesion volume between acute and 24-hour DWI-MRI) (Substudy at Aarhus University Hospital) | 24 hour |
| Difference in Acute (24-hour) Hematoma Expansion in Patients With ICH (Substudy at Aarhus University Hospital) | 24-hour hematoma growth (Difference in hematoma volume between acute and 24-hour CT/MRI) (Substudy at Aarhus University Hospital) | 24 hour |
| Difference in 7 Days Hematoma Volume in Patients With ICH (Substudy at Aarhus University Hospital) | 7-day hematoma reduction (Difference in hematoma volume between acute and 7-day (day 5 to 9) CT ) (Substudy at Aarhus University Hospital) | 7 days |
| Ektacytometry and Analytical Flow Cytometry for eryNOS3 Phosphorylation | Ektacytometry for Erythrocytic Deformability and Analytical Flow Cytometry (FC) for eryNOS3 phosphorylation (pNOS3Ser1177) and s-nitrosylation (-SNO) in RBC | 12 months |
| MicroRNA and Extracellular Vesicle Profile of RIC-induced Neuroprotection | MicroRNA and extracellular vesicle characterization of a possible RIC treatment profile (substudy at Aarhus University Hospital) | 12 months |
| Prehospital microRNA and Extracellular Vesicles (Substudy at Aarhus University Hospital) | Diagnostic abilities of a prehospital microRNA and extracellular vesicles blood samples profile combined with prehospital stroke severity on the differentiation of hemorrhagic from ischemic stroke and to grade ischemic stroke severity | 12 months |
| Prehospital Glial Fibrillary Acidic Protein (Substudy at Aarhus University Hospital) | Predictive abilities of Glial Fibrillary Acidic Protein (GFAP) in prehospital obtained blood samples combined with prehospital stroke severity to differentiate hemorrhagic from ischemic stroke and to grade ischemic stroke severity | 12 months |
| Coagulation Profile of Putative Stroke Patients in Prehospital Obtained Blood Samples | Functional and immunologic plasma assays will be employed to analyze proteins and pathways in coagulation and fibrinolysis (substudy at Aarhus University Hospital) | 12 months |
| Aalborg |
| DK |
| 9000 |
| Denmark |
| Odense University Hospital | Odense | DK | 5000 | Denmark |
| Department of Neurology Regional Hospital West Jutland | Holstebro | DK-7500 | Denmark |
| 32232175 | 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. |
| 37787796 | Result | 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. |
| 38165678 | 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. |
| 38299363 | 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. |
| 41614496 | Derived | 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. |
| 40913213 | 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. |
| 39882626 | 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. |
| FG001 | Sham Remote Ischemic Conditioning | Patients with a prehospital stroke suspicion were randomized and treated with either RIC or sham RIC in the ambulance and continued at the stroke center. Patients with a in-hospital diagnosis of acute ischemic stroke or intracerebral hemorrhage were the target group and study population for the primary endpoint (modified Intention to Treat) |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Remote Ischemic Conditioning | Remote Ischemic Conditioning (Active) |
| BG001 | Sham | Remote Ischemic Conditioning (Sham) |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
| |||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| National Institutes of Health Stroke Scale (NIHSS) | Range 0-42, higher scores indicating more severe neurological symptoms | Median | Inter-Quartile Range | points on NIHSS |
| ||||||||||||||
| Diagnosis | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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.
| Posted | Median | Inter-Quartile Range | units on a scale | 3 months |
|
|
| |||||||||||||||||||||||||||||
| Secondary | Difference Neurological Impairment During the First 24 Hours | Neurological deficits are documented using Prehospital Stroke Score (PreSS). Prehospital Stroke Score is assessed in the the ambulance and at 24-hour or at discharge (if discharge occurs before 24 hours). The PreSS score consists of the Cincinnati Prehospital Stroke Scale (CPSS) with an additional opportunity to report other neurological symptoms (e.g. ataxia, sensory disturbances and visual field loss), and PASS (Prehospital Acute Stroke Severity Scale). The PreSS score range from 0-6, with 6 representing the most severe neurological deficits. | 24-hour difference in prehospital stroke score | Posted | Median | Inter-Quartile Range | units on a scale | 24 hours |
| ||||||||||||||||||||||||||||||
| Secondary | Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Acute Ischemic Stroke | Clinical outcome (modified Rankin Scale) at 3 months in acute stroke patients (target diagnosis) (generalized ordinal logistic regression). TThe 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. | Acute ischemic stroke patients | Posted | Median | Inter-Quartile Range | units on a scale | 3 months |
| ||||||||||||||||||||||||||||||
| Secondary | Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Acute Ischemic Stroke Receiving Reperfusion Therapy | Clinical outcome (modified Rankin Scale) at 3 months inacute ischemic stroke receiving reperfusion therapy (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. | Patients with acute ischemic stroke who were treated with reperfusion therapies (intravenous thrombolysis and/or trombectomy) | Posted | Median | Inter-Quartile Range | units on a scale | 3 months |
| ||||||||||||||||||||||||||||||
| Secondary | Clinical Outcome (Modified Rankin Scale (mRS) at 3 Months in Patients With Intracerebral Hemorrhage (ICH) | Clinical outcome (modified Rankin Scale) at 3 months in patients with intracerebral hemorrhage (ICH) (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. | Patients diagnosed with intracerebral hemorrhage | Posted | Median | Inter-Quartile Range | units on a scale | 3 months |
| ||||||||||||||||||||||||||||||
| Secondary | Difference in Proportion of Patients With Complete Remission of Symptoms Within 24 Hours (TIA; Both With and Without DWI) | Difference in proportion of patients with complete remission of symptoms within 24 hours (TIA; both with and without DWI) Diagnosis of TIA is documented in the electronic case report form | Posted | Count of Participants | Participants | 3 months |
|
| |||||||||||||||||||||||||||||||
| Secondary | Major Adverse Cardiac and Cerebral Events (MACCE) | MACCE is defined as: Cardiovascular events (cardiovascular death, myocardial infarction, acute ischemic or hemorrhagic stroke) Cardiovascular death: Death from known cardiovascular cause or sudden death from unknown cause (no identified cause of death in medical history and/or autopsy) Acute myocardial infarction: Admission with a discharge diagnosis of ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP) Stroke: Admission with a discharge diagnosis of acute ischemic or hemorrhagic stroke. Evaluation is performed using the Danish National Patient Register (LPR) and the DSR at two time points (6 and 15 months after the inclusion of the last patient). Diagnosis of AIS/TIA, ICH and MI (STEMI, NSTEMI, and UAP) are made according to national clinical practice guidelines. | Posted | Count of Participants | Participants | 3 months |
|
| |||||||||||||||||||||||||||||||
| Secondary | Early Neurological Improvement in Acute Ischemic Stroke Patients (AIS) | Reduction in National Institute of Health Stroke Scale (NIHSS) ≥ 4 (baseline versus 24-Hour NIHSS). NIHSS range from 0 to 42, with higher scores representing worse neurological function. | Target population with acute stroke | Posted | Count of Participants | Participants | 24 hours |
|
| ||||||||||||||||||||||||||||||
| Secondary | Early Neurological Improvement in Patients With Intracerebral Hemorrhage (ICH) | Reduction in National Institute of Health Stroke Scale (NIHSS) ≥ 4 (baseline versus 24-Hour NIHSS). NIHSS range from 0 to 42, with higher scores representing worse neurological function. | Not Posted | Dec 2026 | 24 hours | Participants | |||||||||||||||||||||||||||||||||
| Secondary | Quality of Life Measures at 3 Months in AIS and ICH Patients | Quality of life (WHO-5 Well-Being Index) measures in AIS and ICH patients at 3 months | Not Posted | May 2026 | 3 months | Participants | |||||||||||||||||||||||||||||||||
| Secondary | Bed-day Use in AIS and ICH Patients | Bed-day use, measured at 3 months, in AIS and ICH patients | Not Posted | 3 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Three-month and One-year Mortality | All-cause mortality is assessed and subdivided into cardiovascular mortality versus non-cardiovascular mortality | Not Posted | 3 and 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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] | Clinical outcome [modified Rankin Scale (mRS) at 3 months in ischemic stroke patients and the extended remote ischemic postconditioning protocol Ordinal logistic regression analysis will be performed.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.](streamdown:incomplete-link) | Not Posted | Dec 2026 | 3 months | Participants | |||||||||||||||||||||||||||||||||
| Other Pre-specified | 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) | Clinical outcome (modified Rankin Scale (mRS) at 3 months in intracerebral hemorrhage patients and the extended remote ischemic postconditioning protocol 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. | Not Posted | Dec 2026 | 3 months | Participants | |||||||||||||||||||||||||||||||||
| Other Pre-specified | Endovascular Treatment(EVT) -Eligibility (MRI Assessed) in RIC Treated AIS Patients With Large Vessel (Substudy at Aarhus University Hospital) | Proportion of RIC treated AIS patients with large vessel occlusion (LVO) eligible to EVT treatment compared to standard treatment, adjusted for prehospital stroke severity (PreSS) and symptom duration
| Not Posted | 6 hours | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Infarct Growth in AIS Patients (Substudy at Aarhus University Hospital) | 24-hour infarct growth on DWI-MRI (Difference in lesion volume between acute and 24-hour DWI-MRI) (Substudy at Aarhus University Hospital) | Not Posted | 24 hour | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Difference in Acute (24-hour) Hematoma Expansion in Patients With ICH (Substudy at Aarhus University Hospital) | 24-hour hematoma growth (Difference in hematoma volume between acute and 24-hour CT/MRI) (Substudy at Aarhus University Hospital) | Not Posted | 24 hour | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Difference in 7 Days Hematoma Volume in Patients With ICH (Substudy at Aarhus University Hospital) | 7-day hematoma reduction (Difference in hematoma volume between acute and 7-day (day 5 to 9) CT ) (Substudy at Aarhus University Hospital) | Not Posted | 7 days | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Ektacytometry and Analytical Flow Cytometry for eryNOS3 Phosphorylation | Ektacytometry for Erythrocytic Deformability and Analytical Flow Cytometry (FC) for eryNOS3 phosphorylation (pNOS3Ser1177) and s-nitrosylation (-SNO) in RBC | Not Posted | 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | MicroRNA and Extracellular Vesicle Profile of RIC-induced Neuroprotection | MicroRNA and extracellular vesicle characterization of a possible RIC treatment profile (substudy at Aarhus University Hospital) | Not Posted | Dec 2026 | 12 months | Participants | |||||||||||||||||||||||||||||||||
| Other Pre-specified | Prehospital microRNA and Extracellular Vesicles (Substudy at Aarhus University Hospital) | Diagnostic abilities of a prehospital microRNA and extracellular vesicles blood samples profile combined with prehospital stroke severity on the differentiation of hemorrhagic from ischemic stroke and to grade ischemic stroke severity | Not Posted | 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Prehospital Glial Fibrillary Acidic Protein (Substudy at Aarhus University Hospital) | Predictive abilities of Glial Fibrillary Acidic Protein (GFAP) in prehospital obtained blood samples combined with prehospital stroke severity to differentiate hemorrhagic from ischemic stroke and to grade ischemic stroke severity | Not Posted | 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Coagulation Profile of Putative Stroke Patients in Prehospital Obtained Blood Samples | Functional and immunologic plasma assays will be employed to analyze proteins and pathways in coagulation and fibrinolysis (substudy at Aarhus University Hospital) | Not Posted | Dec 2026 | 12 months | Participants |
90 days
Adverse events and adverse device events are defined according to ISO 14155:2011 and European Commission guideline on medical devices (MEDDEV 2.7/3 revision 3).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Remote Ischemic Conditioning (RIC) | Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Remote Ischemic Conditioning | 41 | 713 | 335 | 713 | 54 | 713 |
| EG001 | Sham | Patients with acute ischemic stroke or intracerbreral hemorrhage treated with Sham | 47 | 720 | 325 | 720 | 11 | 720 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| SAE | Cardiac disorders | MEDDEV 2.7/3 | Systematic Assessment | All cause mortality |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper extremity pain during treatment and/or skin petechia | Musculoskeletal and connective tissue disorders | MEDDEV 2.7/3 | Systematic Assessment | Upper extremity pain during treatment and/or skin petechia for ALL randomized (Target diagnosis, non-target diagnosis and post-randomization exlcuded patients) |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Rolf Blauenfeldt | Aarhus University Hospital | 0045 78450000 | rolfblau@rm.dk |
| Feb 12, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D000083242 | Ischemic Stroke |
| D000083302 | Hemorrhagic Stroke |
| D002543 | Cerebral Hemorrhage |
| D002561 | Cerebrovascular Disorders |
| D002493 | Central Nervous System Diseases |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D020300 | Intracranial Hemorrhages |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
|
|
|
|
|
| OG001 | Sham - Remote Ischemic Conditioning | 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.
Usual care with or without acute reperfusion therapy. Sham Remote Ischemic Conditioning: Sham Comparator (Sham-RIC) |
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
|
|