Dataset Information

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

ABSTRACT:

Importance

Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke.

Objective

To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke.

Design, setting, and participants

This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023).

Intervention

The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants.

Main outcomes and measures

The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke.

Results

Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group.

Conclusions and relevance

RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke.

Trial registration

ClinicalTrials.gov Identifier: NCT03481777.

SUBMITTER: Blauenfeldt RA

PROVIDER: S-EPMC10548297 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

Blauenfeldt Rolf Ankerlund RA Hjort Niels N Valentin Jan Brink JB Homburg Anne-Mette AM Modrau Boris B Sandal Birgitte Forsom BF Gude Martin Faurholdt MF Hougaard Kristina Dupont KD Damgaard Dorte D Poulsen Marika M Diedrichsen Tove T Schmitz Marie Louise ML von Weitzel-Mudersbach Paul P Christensen Alex Alban AA Figlewski Krystian K Grove Erik Lerkevang EL Hreiðarsdóttir Margrét Katrín MK Lassesen Henning Morthorst HM Wittrock Daniel D Mikkelsen Søren S Væggemose Ulla U Juelsgaard Palle P Kirkegaard Hans H Rostgaard-Knudsen Martin M Degn Niels N Vestergaard Sigrid Breinholt SB Damsbo Andreas Gammelgaard AG Iversen Ane Bull AB Mortensen Janne Kærgård JK Petersson Jesper J Christensen Thomas T Behrndtz Anne Brink AB Bøtker Hans Erik HE Gaist David D Fisher Marc M Hess David Charles DC Johnsen Søren Paaske SP Simonsen Claus Ziegler CZ Andersen Grethe G

JAMA 20231001 13

<h4>Importance</h4>Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke.<h4>Objective</h4>To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke.<h4>Design, setting, and participants</h4>This was a randomized clinical trial conducted at 4 ...[more]

PMID: 37787796

Similar Datasets

Project description:Background and Aim: Remote ischemic conditioning is a procedure purported to reduce the ischemic injury of an organ. This study aimed to explore the efficiency and safety of remote ischemic conditioning in patients with acute ischemic stroke. We hypothesized that remote ischemic conditioning administered from the first day of hospital admission would improve the infarct volume and clinical outcome at 180 days. Material and Methods: We performed a unicentric double-blind randomized controlled trial. We included all patients consecutively admitted to an Emergency Neurology Department with acute ischemic stroke, ineligible for reperfusion treatment, up to 24 hours from onset. All subjects were assigned to receive secondary stroke prevention treatment along with remote ischemic conditioning on the non-paretic upper limb during the first 5 days of hospitalization, twice daily - a blood pressure cuff placed around the arm was inflated to 20 mmHg above the systolic blood pressure (up to 180 mmHg) in the experimental group and 30 mmHg in the sham group. The primary outcome was the difference in infarct volume (measured on brain CT scan) at 180 days compared to baseline, whereas the secondary outcomes included differences in clinical scores (NIHSS, mRS, IADL, ADL) and cognitive/mood changes (MoCA, PHQ-9) at 180 days compared to baseline. Results: We enrolled 40 patients; the mean age was 65 years and 60% were men. Subjects in the interventional group had slightly better recovery in terms of disability, as demonstrated by the differences in disability scores between admission and 6 months (e.g., the median difference score for Barthel was -10 in the sham group and -17.5 in the interventional group, for ADL -2 in the sham group and -2.5 in the interventional group), as well as cognitive performance (the median difference score for MoCA was -2 in the sham group and -3 in the interventional group), but none of these differences reached statistical significance. The severity of symptoms (median difference score for NIHSS = 5 for both groups) and depression rate (median difference score for PHQ-9 = 0 for both groups) were similar in the two groups. The median difference between baseline infarct volume and final infarct volume at 6 months was slightly larger in the sham group compared to the interventional group (p = 0.4), probably due to an initial larger infarct volume in the former. Conclusion: Our results suggest that remote ischemic conditioning might improve disability and cognition. The difference between baseline infarct volume and final infarct volume at 180 days was slightly larger in the sham group.

Project description:BackgroundRemote ischemic conditioning (RIC) is delivered by a blood pressure cuff over the limb, raising pressure 50 mmHg above the systolic blood pressure, to a maximum of 200 mmHg. The cuff is inflated for five minutes and then deflated for five minutes in a sequential ischemia-reperfusion cycle 4-5 times per session. Elevated pressure in the limb may be associated with discomfort and consequently reduced compliance. Continuous assessment of relative blood concentration and oxygenation with a tissue reflectance spectroscopy (a type of optical sensor device) placed over the forearm during the RIC sessions of the arm will allow us to observe the effect of inflation and deflation of the pressure cuff. We hypothesize, in patients with acute ischemic stroke (AIS) and small vessel disease, RIC delivered together with a tissue reflectance sensor will be feasible.MethodsThe study is a prospective, single-center, randomized control trial testing the feasibility of the device. Patients with AIS within 7 days from symptoms onset; who also have small vessel disease will be randomized 2:1 to intervention or sham control arms. All patients randomized to the intervention arm will receive 5 cycles of ischemia/reperfusion in the non-paralyzed upper limb with a tissue reflectance sensor and patients in the sham control arm will receive pressure by keeping the cuff pressure at 30 mmHg for 5 minutes. A total of 51 patients will be randomized, 17 in the sham control arm and 34 in the intervention arm. The primary outcome measure will be the feasibility of RIC delivered for 7 days or at the time of discharge. The secondary device-related outcome measures are fidelity of RIC delivery and the completion rate of intervention. The secondary clinical outcome includes a modified Rankin scale, recurrent stroke and cognitive assessment at 90 days.DiscussionRIC delivery together with a tissue reflectance sensor will allow insight into the blood concentration and blood oxygenation changes in the skin. This will allow individualized delivery of the RIC and improve compliance.Clinical trial registrationClinicalTrials.gov Identifier: NCT05408130, June 7, 2022.

Project description:BackgroundAcute ischemic stroke (AIS) complicating an acute myocardial infarction (AMI) is not uncommon, but can severely worsen the clinical prognosis. This study aimed to investigate whether remote ischemic conditioning (RIC) could provide clinical benefits to patients with AIS complicating AMI.MethodsSubjects with AIS complicating AMI were recruited in this double-blind, randomized, controlled trial; assigned to the RIC and sham groups; and respectively underwent twice daily RIC and sham RIC for 2 weeks. All subjects received standard medical therapy. The primary endpoint was the rate of major adverse cardiac and cerebrovascular events (MACCEs) within 3 months after enrollment. MACCEs comprise of death from all causes, unstable anginas, AMI, acute ischemic strokes, and transient ischemic attacks.ResultsEighty subjects were randomly assigned; 37 patients in the RIC group and 40 patients in the sham-RIC group completed the 3-month follow-up and were included in the final analysis. Both RIC and sham RIC procedures were well tolerated. At 3-month follow-up, 11 subjects (29.7%) in the RIC group experienced MACCEs compared to 21 (52.5%) in the sham group (hazard ratio [HR], 0.396; 95% confidence interval, 0.187-0.838; adjusted p < 0.05). Six subjects (16.2%) in the RIC group had died at the 3-month follow up, significantly lower than the 15 (37.5%) deaths in the sham group (adjusted HR 0.333; 95% CI 0.126-0.881; p = 0.027). Seventeen subjects (45.9%) in the RIC group and 6 subjects (15.0%) in the sham group achieved functional independence (mRS score ≤ 2) at 3-month follow-up (adjusted OR 12.75; 95% CI 2.104-77.21; p = 0.006).ConclusionsAmong patients with acute ischemic stroke complicating acute myocardial infarction, treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days.Trial registrationURL: www.Clinicaltrialsgov . Unique identifier: NCT03868007. Registered 8 March 2019.

Project description:ImportancePreclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking.ObjectiveTo assess the efficacy of RIC for acute moderate ischemic stroke.Design, setting, and participantsThis multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021.InterventionsEligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971).Main outcomes and measuresThe primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set.ResultsAmong 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group.Conclusions and relevanceAmong adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention.Trial registrationClinicalTrials.gov Identifier: NCT03740971.

Dataset Information

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Intervention

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

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