Evidence map›Paper›PMID 41195862›Full record

Trial reportInternational journal of stroke : official journal of the International Stroke Society2026

Safety and tolerability of Rinvecalinase Alfa (DM199) for acute ischemic stroke (ReMEDy1).

Bruce Cv Campbell, Scott E Kasner, Annette D Lista, John J Volpi, Timothy J Kleinig, Dennis Cordato, Helen M Dewey, Philip Mc Choi, Carlos Garcia-Esperon, Ramesh Sahathevan and 7 more

Registry-linked trialAbstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in International journal of stroke : official journal of the International Stroke Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03290560 (A Randomized, Double-blind, Placebo-controlled Phase II Multi-Center Evaluation to Assess the Safety and Tolerability of DM199 Administered Intravenously and Subcutaneously in Subjects With Acute Ischemic Stroke), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT03290560 phase2completednot on this map

A Randomized, Double-blind, Placebo-controlled Phase II Multi-Center Evaluation to Assess the Safety and Tolerability of DM199 Administered Intravenously and Subcutaneously in Subjects With Acute Ischemic Stroke

TypeinterventionalSponsorDiaMedica Therapeutics IncRan2018 to 2020Enrolled92ConditionsAcute Ischemic StrokeArmsRecombinant human tissue kallikrein, Placebo
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
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

17 authors.

Bruce Cv CampbellDepartment of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.ORCID 0000-0003-3632-9433
Scott E KasnerDivision of Vascular Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Annette D ListaDiaMedica Therapeutics Inc., Minnetonka, MN, USA.
John J VolpiThe Houston Methodist Institute for Academic Medicine, Houston, TX, USA.
Timothy J KleinigDepartment of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia.
Dennis CordatoDepartment of Neurology, Liverpool Hospital, Liverpool, NSW, Australia.
Helen M DeweyDepartment of Neurosciences, Eastern Health and Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.
Philip Mc ChoiDepartment of Neurosciences, Eastern Health and Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.
Carlos Garcia-EsperonDepartment of Neurology, Priority Research Centre for Brain and Mental Health Research, John Hunter Hospital, University of Newcastle, Newcastle, NSW, Australia.ORCID 0000-0001-8843-5890
Ramesh SahathevanDeakin University and St. Vincent's Hospital Melbourne, Fitzroy, VIC, Australia.ORCID 0000-0001-7643-0961
Tissa WijeratneDepartment of Medicine and Neurology, Melbourne Medical School, The University of Melbourne and Western Health, Sunshine Hospital, St Albans, VIC, Australia.
Andrew A WongDepartment of Neurology, Royal Brisbane and Women's Hospital and the University of Queensland, Brisbane, QLD, Australia.
Darshan GhiaFiona Stanley Hospital, Perth, WA, Australia.ORCID 0000-0003-0518-5887
Geoffrey C CloudDepartment of Neuroscience, Alfred Hospital, Prahran, Victoria and Department of Neuroscience, School of Translational Medicine, Momash University, Melbourne, VIC, Australia.ORCID 0000-0002-8365-6907
Michael GiuffreUniversity of Calgary, Departments of Pediatrics and Cardiology, Libin Cardiovascular Institute, Calgary, AB, Canada.
Philip M BathStroke Trials Unit, Mental Health & Clinical Neuroscience, University of Nottingham, Nottingham, UK.ORCID 0000-0003-2734-5132
ReMEDy1 Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRinvecalinase alfa (DM199), a recombinant form of human tissue kallikrein-1 (KLK1), aims to promote local vasodilation to ischemic brain and enhance collateral blood flow. The ReMEDy1 trial tested the safety and tolerability of rinvecalinase alfa in ischemic stroke.

methodsReMEDy1 was a phase II, randomized, double-blind, placebo-controlled, study conducted at 13 Australian sites. Ninety-two patients with NIH Stroke Scale (NIHSS) 6-25 were enrolled within 24 h of ischemic stroke onset. Patients were randomized 1:1 to receive rinvecalinase alfa (1 µg/kg intravenous infusion followed by 3 µg/kg subcutaneously every 3 days for 22 days) or placebo. The primary outcome was safety, assessed by adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included changes in NIHSS, modified Rankin Scale (mRS), and Barthel Index (BI) at Days 22 and 90. Post hoc analyses excluded patients who underwent endovascular therapy (EVT).

resultsThe median age was 72, NIHSS 10, and onset-to-randomization was 19.5 h. SAEs were reported in 20/47 (43.5%) rinvecalinase alfa patients and 14/45 (31.1%) placebo patients. Most patients experienced at least one AE; the most common in the rinvecalinase alfa group were constipation (60.9%), oral candidiasis (23.9%), and nausea (17.4%). Stroke-in-evolution by Day 90 occurred in 0 (0%) rinvecalinase alfa patients versus 6 (13.3%) placebo patients; 4/6 (66.7%) placebo patients with stroke-in-evolution died. No significant differences were observed in secondary efficacy outcomes at Day 90. Post hoc analyses in patients not treated with EVT suggested a tendency toward improved excellent global outcomes with rinvecalinase alfa.

conclusionsRinvecalinase alfa appeared to be safe and generally well-tolerated in ischemic stroke patients, with potential efficacy in reducing stroke progression. Further studies are needed to confirm efficacy and long-term benefits in patients without EVT. REGISTRATIONS: https://www. CLINICALTRIALS: gov/study/NCT03290560.

Indexed as

Brain IschemiaIschemic StrokeStrokeTissue KallikreinsAgedAged, 80 and overDouble-Blind MethodFemaleHumansKallikreinsMaleMiddle AgedRecombinant ProteinsTreatment OutcomeDM199KallikreinsRecombinant ProteinsTissue KallikreinsDM199Ischemic strokerinvecalinase alfa

Identifiers

PMID41195862
PMCPMC13291399

What OpenQuestion holds

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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 OpenQuestion graph.