Trial reportJournal of the American College of Cardiology2003
Effects of ximelagatran, an oral direct thrombin inhibitor, r-hirudin and enoxaparin on thrombin generation and platelet activation in healthy male subjects.
Trial report in Journal of the American College of Cardiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 63 citations in OpenAlex.
- Plasma protein profiling in patients undergoing coronary artery bypass grafting surgery and clinical significance.Oncotarget · 2017Article
- Article
- Dabigatran and left atrial appendage thrombus.Journal of thrombosis and thrombolysis · 2012Review
- Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials.BMJ open · 2012Article
- Heparin-induced thrombocytopenia in the pediatric population: a review of current literature.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2012Article
- Direct thrombin inhibitors: pharmacology and application in intensive care medicine.Intensive care medicine · 2010Review
- Anti-thrombin therapy during warm ischemia and cold preservation prevents chronic kidney graft fibrosis in a DCD model.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2010Article
- [Direct thrombin inhibitors: pharmacology and application in cardiovascular anesthesia].Der Anaesthesist · 2008Review
- Computationally derived points of fragility of a human cascade are consistent with current therapeutic strategies.PLoS computational biology · 2007Article
- Article
- Bivalirudin in percutaneous coronary intervention.Vascular health and risk management · 2006Review
- Review
- A review of the clinical uses of ximelagatran in thrombosis syndromes.Journal of thrombosis and thrombolysis · 2003Review
Corrections and comments
- Commented on by
Authors and funding
10 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThe effects of ximelagatran, an oral direct thrombin inhibitor (DTI), recombinant hirudin (r-hirudin) and enoxaparin on thrombin generation and platelet activation were studied in humans.
backgroundRecombinant hirudin (parenteral DTI) and enoxaparin (low molecular weight heparin) have been demonstrated to be clinically effective in acute coronary syndromes. Ximelagatran is currently under investigation for the prevention and treatment of thromboembolism. The shed blood model allows for the study of thrombin generation and platelet activation in humans in vivo.
methodsThis was an open-label, parallel-group study involving 120 healthy male volunteers randomized to receive one of three oral doses of ximelagatran (15, 30 or 60 mg), r-hirudin (intravenous) or enoxaparin (subcutaneous) at doses demonstrated to be clinically effective in acute coronary syndromes, or to serve as a control. Thrombin generation (prothrombin fragment 1+2 [F1+2] and thrombin-antithrombin complex [TAT]) and platelet activation (beta-thromboglobulin [beta-TG]) biomarkers were studied using a shed blood model involving blood collection from skin incisions made using standardized bleeding time devices.
resultsOral ximelagatran, intravenous r-hirudin and subcutaneous enoxaparin rapidly and significantly (p < 0.05) decreased F1+2, TAT and beta-TG levels in shed blood, indicating inhibition of thrombin generation and platelet activation. Statistically significant concentration (melagatran, the active form of ximelagatran)-response relationships for F1+2 (p = 0.005), TAT (p = 0.005) and beta-TG (p < 0.001) levels, with IC(50)s of 0.376 (F1+2), 0.163 (TAT) and 0.115 (beta-TG) micromol/l, were detected. Melagatran showed dose-proportional pharmacokinetics with low variability. All drugs were well tolerated.
conclusionsOral administration of the DTI ximelagatran resulted in a rapid inhibition of both thrombin generation and platelet activation in a concentration-dependent manner using a human shed blood model. The inhibition of thrombin generation by 60 mg ximelagatran was comparable to that observed with doses of r-hirudin and enoxaparin demonstrated to be effective for the treatment of acute coronary syndromes.
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.