Evidence map›Paper›PMID 42707803›Full record

ArticleStroke (Hoboken, N.J.)2026

Remote Ischemic Conditioning in Patients With Acute Ischemic Stroke Ineligible for Recanalization Therapies: A Phase II Trial.

Susanna Diamanti, Mauro Tettamanti, Raffaele Ornello, Francesco Andrea Pedrazzini, Matteo Farè, Enrico Colangeli, Cindy Tiseo, Gabriele Mainini, Angela Giglio, Caterina Sozzi and 14 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stroke (Hoboken, N.J.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04400981 (Multi-center Randomized Pilot Clinical Trial on Remote Ischemic Conditioning in Acute Ischemic Stroke Within 9 Hours of Onset in Patients Ineligible to Recanalization Therapies), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04400981 nacompletednot on this map

Multi-center Randomized Pilot Clinical Trial on Remote Ischemic Conditioning in Acute Ischemic Stroke Within 9 Hours of Onset in Patients Ineligible to Recanalization Therapies

TypeinterventionalSponsorUniversity of Milano BicoccaRan2021 to 2024Enrolled80ConditionsIschemic StrokeArmsRemote ischemic conditioning, standard medical therapy
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Susanna DiamantiDepartment of Neurology, Fondazione San Gerardo dei Tintori, Istituto di Ricovero e Cura a Carattere Scientifico, Monza, Italy (S.D., C.F., S.B.).ORCID https://orcid.org/0000-0002-6201-1536
Mauro TettamantiLaboratorio di Epidemiologia Geriatrica, Dipartimento di Politiche per la Salute, Istituto di Ricerche Farmacologiche Mario Negri, Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy (M.T., M.C.).ORCID https://orcid.org/0000-0001-7345-0887
Raffaele OrnelloDepartment of Applied Clinical Sciences and Biotechnology, University of L'Aquila, Italy (R.O., S.S.).ORCID https://orcid.org/0000-0001-9501-4031
Francesco Andrea PedrazziniDepartment of Medicine and Surgery, University of Milano-Bicocca, Italy (F.A.P., M.F., G.M., A.G., C.S., C.B., C.P.Z., J.M., C.F., S.B.).ORCID https://orcid.org/0009-0009-7575-2569
Matteo FarèDepartment of Medicine and Surgery, University of Milano-Bicocca, Italy (F.A.P., M.F., G.M., A.G., C.S., C.B., C.P.Z., J.M., C.F., S.B.).ORCID https://orcid.org/0000-0001-8956-7406
Enrico ColangeliDepartment of Neurology and Stroke Unit, Avezzano Hospital, Azienda Sanitaria Locale 1 Abruzzo, Italy (R.O., E.C., C.T., S.S.).ORCID https://orcid.org/0000-0002-8696-9407
Cindy TiseoDepartment of Neurology and Stroke Unit, Avezzano Hospital, Azienda Sanitaria Locale 1 Abruzzo, Italy (R.O., E.C., C.T., S.S.).
Gabriele MaininiDepartment of Medicine and Surgery, University of Milano-Bicocca, Italy (F.A.P., M.F., G.M., A.G., C.S., C.B., C.P.Z., J.M., C.F., S.B.).
Angela GiglioDepartment of Medicine and Surgery, University of Milano-Bicocca, Italy (F.A.P., M.F., G.M., A.G., C.S., C.B., C.P.Z., J.M., C.F., S.B.).
Caterina SozziDepartment of Medicine and Surgery, University of Milano-Bicocca, Italy (F.A.P., M.F., G.M., A.G., C.S., C.B., C.P.Z., J.M., C.F., S.B.).
Federica FerrariDepartment of Stroke Unit and Emergency Neurology, Istituto di Ricovero e Cura a Carattere Scientifico Mondino Foundation, Pavia, Italy (F.F., A.C.).ORCID https://orcid.org/0000-0002-9868-5997
Mario BecciaNEuroscienze Salute Mentale e Organi di Senso (NESMOS) Department, Faculty of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University of Rome, Roma, Italy (M.B., G.S.).
Elisa BianchiLaboratorio di Malattie Neurologiche, Dipartimento di Neuroscienze, Istituto di Ricerche Farmacologiche Mario Negri, Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy (E.B.).ORCID https://orcid.org/0000-0002-0279-0128
Anna BersanoCerebrovascular Unit Fondazione Istituto Neurologico Carlo Besta, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy (A.B.).ORCID https://orcid.org/0000-0002-2493-628X
Chiara BazziniDepartment of Medicine and Surgery, University of Milano-Bicocca, Italy (F.A.P., M.F., G.M., A.G., C.S., C.B., C.P.Z., J.M., C.F., S.B.).
Massimo CartabiaLaboratorio di Epidemiologia Geriatrica, Dipartimento di Politiche per la Salute, Istituto di Ricerche Farmacologiche Mario Negri, Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy (M.T., M.C.).ORCID https://orcid.org/0000-0002-3794-4772
Chiara Paola ZoiaDepartment of Medicine and Surgery, University of Milano-Bicocca, Italy (F.A.P., M.F., G.M., A.G., C.S., C.B., C.P.Z., J.M., C.F., S.B.).ORCID https://orcid.org/0000-0003-1654-4996
Jacopo MarianiDepartment of Medicine and Surgery, University of Milano-Bicocca, Italy (F.A.P., M.F., G.M., A.G., C.S., C.B., C.P.Z., J.M., C.F., S.B.).ORCID https://orcid.org/0000-0001-9715-1291
Giuseppe PignataroDivision of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, Napoli, Italy (G.P.).ORCID https://orcid.org/0000-0002-7290-4397
Anna CavalliniDepartment of Stroke Unit and Emergency Neurology, Istituto di Ricovero e Cura a Carattere Scientifico Mondino Foundation, Pavia, Italy (F.F., A.C.).ORCID https://orcid.org/0000-0002-5227-1502
Giuliano SetteNEuroscienze Salute Mentale e Organi di Senso (NESMOS) Department, Faculty of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University of Rome, Roma, Italy (M.B., G.S.).
Simona SaccoDepartment of Applied Clinical Sciences and Biotechnology, University of L'Aquila, Italy (R.O., S.S.).ORCID https://orcid.org/0000-0003-0651-1939
Carlo FerrareseDepartment of Neurology, Fondazione San Gerardo dei Tintori, Istituto di Ricovero e Cura a Carattere Scientifico, Monza, Italy (S.D., C.F., S.B.).ORCID https://orcid.org/0000-0002-7499-6600
Simone BerettaDepartment of Neurology, Fondazione San Gerardo dei Tintori, Istituto di Ricovero e Cura a Carattere Scientifico, Monza, Italy (S.D., C.F., S.B.).ORCID https://orcid.org/0000-0002-9417-2748

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRemote ischemic conditioning (RIC) has shown neuroprotective potential in preclinical stroke models. In patients with acute ischemic stroke, trials report heterogeneous results, supporting ongoing debate about clinical efficacy, especially in those ineligible for recanalization. This trial assessed RIC benefit in this population and evaluated HSP27 (heat shock protein 27) and HIF-1α (hypoxia-inducible factor 1-alpha) as biomarkers of RIC-related biological activity.

methodsThis was a multicenter, phase II, proof-of-concept, block-randomized, controlled, parallel-arm, PROBE (Prospective Randomized Open Blinded End Point)-designed clinical trial. Patients with acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 5-25) who were ineligible for recanalization therapies were randomized 1:1 within 9 hours of symptom onset to RIC (4 5-minute cycles of upper-arm ischemia/reperfusion) plus standard medical therapy or standard therapy alone. The primary outcome was the percentage change in NIHSS score at 72 hours. Secondary outcomes included NIHSS score changes at 24 and 48 hours, 90-day modified Rankin Scale, tolerability, and changes in plasma HSP27 and HIF-1α concentrations from 24 to 72 hours.

resultsEighty patients (40 per group) were enrolled across 4 centers from August 2021 to March 2024. Although slightly in favor of RIC treatment, median NIHSS score percentage change at 72 hours did not differ between the RIC and control groups (23.6% versus 29.9%; adjusted coefficient, -3.8 [95% CI, -19.7 to 12.1];

conclusionsIn patients with acute ischemic stroke ineligible for recanalization therapies, early RIC was safe, feasible, and well tolerated but did not improve neurological outcomes or modify HIF-1α and HSP27 levels. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04400981.

Indexed as

acute ischemic strokebiomarkersischemianeuroprotectionreperfusion

Identifiers

PMID42707803
PMCPMC13549644

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.