Remote Ischemic Conditioning in Patients With Acute Stroke (RESIST)
Λέξεις-κλειδιά
Αφηρημένη
Περιγραφή
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.
Ημερομηνίες
| Τελευταία επαλήθευση: | 03/31/2020 |
| Πρώτα υποβλήθηκε: | 03/11/2018 |
| Υποβλήθηκε εκτιμώμενη εγγραφή: | 03/21/2018 |
| Δημοσιεύτηκε για πρώτη φορά: | 03/28/2018 |
| Υποβλήθηκε τελευταία ενημέρωση: | 04/29/2020 |
| Δημοσιεύτηκε η τελευταία ενημέρωση: | 04/30/2020 |
| Ημερομηνία έναρξης της πραγματικής μελέτης: | 04/02/2018 |
| Εκτιμώμενη κύρια ημερομηνία ολοκλήρωσης: | 12/30/2022 |
| Εκτιμώμενη ημερομηνία ολοκλήρωσης μελέτης: | 12/30/2024 |
Κατάσταση ή ασθένεια
Παρέμβαση / θεραπεία
Device: Remote Ischemic Conditioning
Device: Sham - Remote Ischemic Conditioning
Φάση
Ομάδες βραχιόνων
| Μπράτσο | Παρέμβαση / θεραπεία |
|---|---|
| Active Comparator: Remote Ischemic Conditioning 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 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. |
| Sham Comparator: 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.
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 Sham Comparator (Sham-RIC) |
Κριτήρια καταλληλότητας
| Επιλέξιμες ηλικίες για μελέτη | 18 Years Προς την 18 Years |
| Φύλα επιλέξιμα για μελέτη | All |
| Δέχεται υγιείς εθελοντές | Ναί |
| Κριτήρια | Inclusion Criteria: - 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) Exclusion Criteria: - 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 |
Αποτέλεσμα
Πρωτεύοντα αποτελέσματα
1. Clinical outcome (mRS) at 3 months in acute stroke (AIS and ICH) [3 months]
Δευτερεύοντα αποτελέσματα
1. Difference neurological impairment during the first 24 hours in all randomized patients [24 hours]
2. Clinical outcome (modified Rankin Scale (mRS) at 3 months in acute ischemic stroke [3 months]
3. Clinical outcome (modified Rankin Scale (mRS) at 3 months in acute ischemic stroke receiving reperfusion therapy [3 months]
4. Clinical outcome (modified Rankin Scale (mRS) at 3 months in patients with intracerebral hemorrhage (ICH) [3 months]
5. Difference in proportion of patients with complete remission of symptoms within 24 hours (TIA; both with and without DWI) [3 months]
6. Major Adverse Cardiac and Cerebral Events (MACCE) and recurrent ischemic events based on registry data at 3 and 12 months in ICH, AIS patients, TIA and non-vascular diagnosis [12 months]
7. Early neurological improvement in acute ischemic stroke patients (AIS) [24 hours]
8. Early neurological improvement in patients with intracerebral hemorrhage (ICH) [24 hours]
9. Quality of life measures at 3 months in AIS and ICH patients [3 months]
10. Bed-day use in AIS and ICH patients [3 months]
11. Three-month and one-year mortality [3 and 12 months]
Άλλα μέτρα αποτελεσμάτων
1. 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]
2. 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]
3. Endovascular treatment(EVT) -eligibility (MRI assessed) in RIC treated AIS patients with large vessel (substudy at Aarhus University Hospital) [6 hours]
4. Infarct growth in AIS patients (substudy at Aarhus University Hospital) [24 hour]
5. Difference in acute (24-hour) hematoma expansion in patients with ICH (substudy at Aarhus University Hospital) [24 hour]
6. Difference in 7 days hematoma volume in patients with ICH (substudy at Aarhus University Hospital) [7 days]
7. Ektacytometry and Analytical Flow Cytometry for eryNOS3 phosphorylation [12 months]
8. MicroRNA and extracellular vesicle profile of RIC-induced neuroprotection (substudy at Aarhus University Hospital) [12 months]
9. Prehospital microRNA and extracellular vesicles (substudy at Aarhus University Hospital) [12 months]
10. Prehospital Glial Fibrillary Acidic Protein (substudy at Aarhus University Hospital) [12 months]
11. Coagulation profile of putative stroke patients in prehospital obtained blood samples (substudy at Aarhus University Hospital) [12 months]
