Trial reportJCI insight2019
Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer.
Trial report in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02195232 (Randomized, Placebo-controlled, Double-blind Phase II/III Trial of Oral Isoquercetin to Prevent Venous Thromboembolic Events in Cancer Patients.), which is not on this map. Cited by 88 papers, 2 of them syntheses that pooled 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.
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.
Randomized, Placebo-controlled, Double-blind Phase II/III Trial of Oral Isoquercetin to Prevent Venous Thromboembolic Events in Cancer Patients.
Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 162 citations in OpenAlex.
- Kaempferol, Myricetin and Fisetin in Prostate and Bladder Cancer: A Systematic Review of the Literature.Nutrients · 2021Pooled it
- Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.The Cochrane database of systematic reviews · 2020Pooled it
- Isoquercetin for thromboinflammation in sickle cell disease: a randomized double-blind placebo-controlled trial.Blood advances · 2024Trial
- Molecular mechanisms of protein disulfide isomerase antagonism by punicalagin.Biochemical and biophysical research communications · 2026Article
- Article
- Luminespib and AZ5104 are effective antithrombotic drugs via targeting the platelet Ero1α-PDI pathway.Science advances · 2026Article
- PDIA1 promotes androgen receptor activation and prostate cancer cell survival through enhancing HMMR stability.FEBS letters · 2026Article
- Polyphenols in food and food wastes: Extraction, isolation, and health applications.Food chemistry. Molecular sciences · 2026Review
- A monoclonal antibody to platelet αIIbβ3 that inhibits protein disulfide isomerase binding and platelet aggregation.Blood advances · 2026Article
- Molecular insights into protein disulfide isomerase antagonism by punicalagin.bioRxiv : the preprint server for biology · 2026Article
- Article
- Pharmacological Management of Thrombosis: Current State and Future Strategies.International journal of molecular sciences · 2026Review
- Hemostasis-Sparing Antiplatelet Therapy: Current Concepts and Emerging Targets in Arterial Thrombosis.Biomolecules & therapeutics · 2026Review
- The crucial role of thromboxane AFrontiers in pharmacology · 2026Review
- Major Plant-Based Compounds for the Prevention and Treatment of Melanoma-A Mini Review.Biology · 2025Review
- Protein disulfide isomerases regulate androgen receptor stability and promote prostate cancer cell growth and survival.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Thiol Isomerases: Enzymatic Mechanisms, Models of Oxidation, and Antagonism by Galloylated Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Mitigation of hypobaric hypoxia induced renal inflammatory alterations by quercetin prophylaxis.Journal of traditional and complementary medicine · 2025Article
- Extracellular PDI in thrombosis and vascular injury.Thrombosis journal · 2025Review
- In situ protein corona-camouflaged supramolecular assemblies remodel thrombotic microenvironment for improved arterial homeostasis.Science advances · 2025Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 10 institutions in 2 countries.
Funding
Abstract
backgroundProtein disulfide isomerase (PDI) is a thiol isomerase secreted by vascular cells that is required for thrombus formation. Quercetin flavonoids inhibit PDI activity and block platelet accumulation and fibrin generation at the site of a vascular injury in mouse models, but the clinical effect of targeting extracellular PDI in humans has not been studied.
methodsWe conducted a multicenter phase II trial of sequential dosing cohorts to evaluate the efficacy of targeting PDI with isoquercetin to reduce hypercoagulability in cancer patients at high risk for thrombosis. Patients received isoquercetin at 500 mg (cohort A, n = 28) or 1000 mg (cohort B, n = 29) daily for 56 days, with laboratory assays performed at baseline and the end of the study, along with bilateral lower extremity compression ultrasound. The primary efficacy endpoint was a reduction in D-dimer, and the primary clinical endpoint included pulmonary embolism or proximal deep vein thrombosis.
resultsThe administration of 1000 mg isoquercetin decreased D-dimer plasma concentrations by a median of -21.9% (P = 0.0002). There were no primary VTE events or major hemorrhages observed in either cohort. Isoquercetin increased PDI inhibitory activity in plasma (37.0% in cohort A, n = 25, P < 0.001; 73.3% in cohort B, n = 22, P < 0.001, respectively). Corroborating the antithrombotic efficacy, we also observed a significant decrease in platelet-dependent thrombin generation (cohort A median decrease -31.1%, P = 0.007; cohort B median decrease -57.2%, P = 0.004) and circulating soluble P selectin at the 1000 mg isoquercetin dose (median decrease -57.9%, P < 0.0001).
conclusionsIsoquercetin targets extracellular PDI and improves markers of coagulation in advanced cancer patients.
trial registrationClinicaltrials.gov NCT02195232.
fundingQuercegen Pharmaceuticals; National Heart, Lung, and Blood Institute (NHLBI; U54HL112302, R35HL135775, and T32HL007917); and NHLBI Consortium Linking Oncology and Thrombosis (U01HL143365).
Indexed as
Identifiers
What OpenQuestion holds
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.