Evidence map›Paper›PMID 32844723›Full record

Trial reportJournal of the American Heart Association2020

First Human Use of RUC-4: A Nonactivating Second-Generation Small-Molecule Platelet Glycoprotein IIb/IIIa (Integrin αIIbβ3) Inhibitor Designed for Subcutaneous Point-of-Care Treatment of ST-Segment-Elevation Myocardial Infarction.

Dean J Kereiakes, Tim D Henry, Anthony N DeMaria, Ohad Bentur, Marilyn Carlson, Corinne Seng Yue, Linda H Martin, Jeff Midkiff, Michele Mueller, Terah Meek and 3 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of the American Heart Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.6field-weighted citation impact, top 5% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 41 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction.EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology · 2021
    Trial
  4. Trial
  5. Mass balance and metabolite profiling ofXenobiotica; the fate of foreign compounds in biological systems · 2026
    Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Dual Antiplatelet Therapy with Parenteral P2YJournal of cardiovascular development and disease · 2023
    Review
  16. Article
  17. Review
  18. Review
  19. Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023
    Review
  20. INTEGRINS: A BEDSIDE TO BENCH TO BEDSIDE STORY.Transactions of the American Clinical and Climatological Association · 2023
    Article
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

13 authors at 5 institutions in 1 country.

Dean J KereiakesThe Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH.
Tim D HenryThe Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH.
Anthony N DeMariaUC San Diego Health La Jolla CA.
Ohad BenturAllen and Frances Adler Laboratory of Blood and Vascular Biology Rockefeller University New York NY.
Marilyn CarlsonPrecision for Medicine Carlsbad CA.
Corinne Seng YueLearn and Confirm Inc. Saint-Laurent Quebec Canada.
Linda H MartinThe Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH.
Jeff MidkiffThe Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH.
Michele MuellerThe Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH.
Terah MeekThe Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH.
Deborah GarzaThe Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH.
C Michael GibsonBoston Clinical Research Institute Newton MA.
Barry S CollerAllen and Frances Adler Laboratory of Blood and Vascular Biology Rockefeller University New York NY.
Christ Hospital · USRockefeller University · USClinical Research Institute · USPrecision for Medicine (United States) · USUC San Diego Health System · US

Funding

Transforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8M
Platelet Integrin AlphaIIbBeta3 Structure, Activation, and Ligand Binding: Fibrinogen, Fibrin, D-dimer, and von Willebrand FactorR01HL019278 · NHLBI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Claudia Lorena Buitrago, Barry Coller · 1985 to 2026
$17.6M
NCATS NIH HHS UL1 TR000043NHLBI NIH HHS R01 HL019278
6 · The paper itself

Abstract

Background Despite reductions in door-to-balloon times for primary coronary intervention, mortality from ST-segment-elevation myocardial infarction has plateaued. Early pre-primary coronary intervention treatment of ST-segment-elevation myocardial infarction with glycoprotein IIb/IIIa inhibitors improves pre-primary coronary intervention coronary flow, limits infarct size, and improves survival. We report the first human use of a novel glycoprotein IIb/IIIa inhibitor designed for subcutaneous first point-of-care ST-segment-elevation myocardial infarction treatment. Methods and Results Healthy volunteers and patients with stable coronary artery disease receiving aspirin received escalating doses of RUC-4 or placebo in a sentinel-dose, randomized, blinded fashion. Inhibition of platelet aggregation (IPA) to ADP (20 μmol/L), RUC-4 blood levels, laboratory evaluations, and clinical assessments were made through 24 hours and at 7 days. Doses were increased until reaching the biologically effective dose (the dose producing ≥80% IPA within 15 minutes, with return toward baseline within 4 hours). In healthy volunteers, 15 minutes after subcutaneous injection, mean±SD IPA was 6.9%+7.1% after placebo and 71.8%±15.0% at 0.05 mg/kg (n=6) and 84.7%±16.7% at 0.075 mg/kg (n=6) after RUC-4. IPA diminished over 90 to 120 minutes. In patients with coronary artery disease, 15 minutes after subcutaneous injection of placebo or 0.04 mg/kg (n=2), 0.05 mg/kg (n=6), and 0.075 mg/kg (n=18) of RUC-4, IPA was 14.6%±11.7%, 53.6%±17.0%, 76.9%±10.6%, and 88.9%±12.7%, respectively. RUC-4 blood levels correlated with IPA. Aspirin did not affect IPA or RUC-4 blood levels. Platelet counts were stable and no serious adverse events, bleeding, or injection site reactions were observed. Conclusions RUC-4 provides rapid, high-grade, limited-duration platelet inhibition following subcutaneous administration that appears to be safe and well tolerated. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NTC03844191.

Indexed as

AdultAgedAspirinCase-Control StudiesCoronary Artery DiseaseFemaleHumansInjections, SubcutaneousMaleMiddle AgedPlacebosPlatelet Aggregation InhibitorsPlatelet CountPlatelet Glycoprotein GPIIb-IIIa ComplexPoint-of-Care SystemsPyrimidinonesAspirinPlacebosPlatelet Aggregation InhibitorsPlatelet Glycoprotein GPIIb-IIIa ComplexPyrimidinonesRUC-4 compoundThiadiazolesGPIIb/IIIamyocardial infarctionplatelet inhibitorSTEMI

Identifiers

PMID32844723
PMCPMC7660780
OpenAlexW3080814849

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.