Trial reportPloS one2014
Platelet aggregation unchanged by lipoprotein-associated phospholipase A₂ inhibition: results from an in vitro study and two randomized phase I trials.
Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 8 papers, 1 of them a synthesis 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.
A Double Blind, Placebo Controlled, Parallel Study to Evaluate Effects of Repeat Doses of Rilapladib on Platelet Aggregation in Healthy Male Volunteers
A Double Blind Study to Evaluate Effects of Repeat Doses of SB-659032 on Platelet Aggregation in Healthy Volunteers
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis.European journal of nuclear medicine and molecular imaging · 2016Guideline
- Independent association of Lp(a) with platelet reactivity in subjects without statins or antiplatelet agents.Scientific reports · 2022Article
- A multitude of signaling pathways associated with Alzheimer's disease and their roles in AD pathogenesis and therapy.Medicinal research reviews · 2021Review
- Lipoprotein-associated phospholipase A2: The story continues.Medicinal research reviews · 2020Review
- Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: AnFrontiers in microbiology · 2020Article
- Failure to Launch: Targeting Inflammation in Acute Coronary Syndromes.JACC. Basic to translational science · 2017Review
- Investigation of a Bicyclo[1.1.1]pentane as a Phenyl Replacement within an LpPLAACS medicinal chemistry letters · 2017Article
- PET imaging of inflammation in atherosclerosis.Nature reviews. Cardiology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe explored the theorized upregulation of platelet-activating factor (PAF)- mediated biologic responses following lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibition using human platelet aggregation studies in an in vitro experiment and in 2 clinical trials. METHODS AND
resultsFull platelet aggregation concentration response curves were generated in vitro to several platelet agonists in human plasma samples pretreated with rilapladib (selective Lp-PLA2 inhibitor) or vehicle. This was followed by a randomized, double-blind crossover study in healthy adult men (n = 26) employing a single-agonist dose assay of platelet aggregation, after treatment of subjects with 250 mg oral rilapladib or placebo once daily for 14 days. This study was followed by a second randomized, double-blind parallel-group trial in healthy adult men (n = 58) also treated with 250 mg oral rilapladib or placebo once daily for 14 days using a full range of 10 collagen concentrations (0-10 µg/ml) for characterizing EC50 values for platelet aggregation for each subject. Both clinical studies were conducted at the GlaxoSmithKline Medicines Research Unit in the Prince of Wales Hospital, Sydney, Australia. EC50 values derived from multiple agonist concentrations were compared and no pro-aggregant signals were observed during exposure to rilapladib in any of these platelet studies, despite Lp-PLA2 inhibition exceeding 90%. An increase in collagen-mediated aggregation was observed 3 weeks post drug termination in the crossover study (15.4% vs baseline; 95% confidence interval [CI], 3.9-27.0), which was not observed during the treatment phase and was not observed in the parallel-group study employing a more robust EC50 examination.
conclusionsLp-PLA2 inhibition does not enhance platelet aggregation.
trial registration1) Study 1: ClinicalTrials.gov NCT01745458 2) Study 2: ClinicalTrials.gov NCT00387257.
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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.