The influence of naloxone on pharmacokinetics and pharmacodynamics of ticagrelor in patients with unstable angina pectoris receiving concomitant treatment with morphine — a protocol of a randomized trial

Rapid platelet inhibition plays pivotal role in contemporary treatment of patients presenting with acute coronary syndromes. Morphine, the most commonly used analgesic has been proven to impair both absorption and onset of action of P2Y12 receptor inhibitors, which can be described as “the morphine effect”. Most negative effects of morphine are caused by its undesirable influence on gastrointestinal tract. We hypothesized that naloxone, widely administered intravenous opioid reversing drug, may turn out to be beneficial if given orally in acute coronary syndrome patients previously treated with morphine. Therefore, a phase IV, randomized pilot study was designed so as to evaluate the impact of naloxone administration on pharmacokinetics and pharmacodynamics of P2Y12 inhibitor, ticagrelor in unstable angina patients. A group of 30 consecutive unstable angina patients treated with ticagrelor and morphine will be randomized in a 1:1 ratio into the study arms. To the best of our knowledge, no such approaches to overcome negativeinfluence of morphine in acute coronary syndrome patients have been described in literature so far

Impact of ticagrelor administration strategy on its pharmacokinetics and pharmacodynamics in patients with unstable angina pectoris: a protocol of a randomized study

Introduction. Dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor constitutes an essential part of the management of patients with acute coronary syndromes (ACS). Based on the favorable results of the PLATO trial, ticagrelor is currently recommended as the first line P2Y12 receptor inhibitor in a broad spectrum of ACS patients. According to the recently published data, several conditions, including concurrent analgesia with morphine and clinical presentation as an ACS, may alter ticagrelor absorption and its antiplatelet effect. Therefore, the goal of the present study was to investigate pharmacokinetics and pharmacodynamics of new ticagrelor administration strategies aimed to overcome limitations of the standard ticagrelor loading regimen. Methods/design. The study is designed as a phase IV, single center, randomized, investigator-initiated, parallel-group, open-label, interventional study comparing the influence of various ticagrelor administration strategies on its pharmacokinetics and pharmacodynamics. Patients with unstable angina pectoris will be randomized in a 1:1:1 ratio into one of three arms, each receiving a 180 mg ticagrelor loading dose (LD). Ticagrelor administration strategies comprise: 1) pulverized ticagrelor administered sublingually, 2) pulverized ticagrelor in 10 mL suspension in tap water administered orally and 3) integral ticagrelor tablets administered orally. An internal pilot study including 30 (10 in each of the arms) is planned in order to determine the final sample size. The primary endpoint of the trial is time (tmax) required for ticagrelor and its active metabolite AR-C124900XX to reach maximum plasma concentration within time frame of six hours after administration of ticagrelor LD. The secondary endpoints include ticagrelor and AR-C124900XX maximum plasma concentration, area under the plasma concentration-time curve for ticagrelor and AR-C124900XX (AUC 0–6h) and platelet reactivity assessed with Multiple Electrode Aggregometry using the Multiplate™ Analyzer prior to and within time frame of six hours following ticagrelor LD. Discussion. This study is expected to provide essential evidence-based data on the impact of ticagrelor administration strategy on its pharmacokinetics and pharmacodynamics in patients with unstable angina pectoris. Hopefully, based on its results, further clinical outcome-powered trials on new ticagrelor administration strategies will be designed and conducted.

Perioperative nutrition according to the ERAS protocol

Protocol ERAS - "Enhanced Recovery after Surgery" - is a modern multidisciplinary formula of perioperative care to improve treatment outcomes. Over the past few years, many attempts have been made to implement recommendations for the management of patients in the perioperative period. They were primarily aimed at improving the results of treatment of patients undergoing surgery, and thus shorteninglength of stay in hospital, and - as a consequence - reducing the risk of developing complications and even the number of deaths. One of the first author who noticed effectiveness of multimodal treatment for a faster recovery and a shorter stay in the hospital was Professor Henrik Kehlet from the University of Copenhagen. He emphasized that in order to understand the nature of complications occurring in patients undergoing surgery, the basis of the factors responsible for the response to the surgical trauma should be known. In the late 1990s, Kehlet postulated that steps should be taken to introduce a comprehensive program including, among others: effective anesthesia, early rehabilitation of the patient, reduction of surgical stress, or quick restoration of nutrition via the gastrointestinal tract. The comprehensive perioperative care protocol for improving the treatment results requires the need for cooperation of specialists and all medical staff related to perioperative care - not only a surgeon or anesthetist, but also a physiotherapist or dietitian

The influence of metoclopramide on pharmacokinetics and pharmacodynamics of ticagrelor in patients with unstable angina pectoris receiving concomitant treatment with morphine — a protocol of a randomized trial

Introduction. Nowadays, due to the “morphine effect”, the screening of methods that provide quick and effective platelet inhibition with oral P2Y12 inhibitors administrated simultaneously with morphine in patients with acute coronary syndromes are extensively investigated by numerous scientists. Metoclopramide, which stimulates the motility of gastrointestinal tract, may become a potential method of overcoming the negative morphine effect. The present study was designed to demonstrate the influence of metoclopramide administration on the pharmacokinetic and pharmacodynamic profile of ticagrelor between patients with unstable angina pectoris treated with morphine and crushed ticagrelor. Methods/design. A study was designed as a phase IV, single-centre, randomized, investigator-initiated, parallel-group, open-label, interventional trial. Patients will be randomized in a 1:1 manner into two arms: 1) patients treated with a combination of crushed ticagrelor and morphine and 2) patients treated with a combination of crushed ticagrelor followed by morphine and metoclopramide. Blood sample collection will be scheduled directly before the administration of ticagrelor loading dose and 15, 30, 45, 60, 120, 180, 240, and 360 minutes after the loading dose. Pharmacokinetic and pharmacodynamic assessment of ticagrelor and its active metabolite will be evaluated in all pre-defined time points. Discussion. The current study is, to our knowledge, the first one to provide data on the influence of metoclopramide in patients with acute coronary syndromes, who received intravenous opioid analgesia. It is expected to contribute to the development of contemporary knowledge on the treatment of patients presenting with acute coronary syndromes, and should enable clinicians to implement strategies of quick platelet inhibition

Oral NAloxone to overcome the moRphine effect in acute COronary syndrome patients treated with TICagrelor — NARCOTIC trial

Background: Numerous worldwide clinical trials have proven the indisputably negative influence of morphine on the pharmacokinetics and pharmacodynamics of P2Y12 receptor inhibitors in patients presenting with acute coronary syndromes. The aim of this trial was to evaluate whether oral co-administration of an anti-opioid agent, naloxone, can be considered a successful approach to overcome ‘the morphine effect’. Methods: Consecutive unstable angina patients receiving ticagrelor and morphine with or without orally administered naloxone underwent assessment of platelet reactivity using Multiplate analyzer as well as evaluation of the pharmacokinetic profile of ticagrelor and its active metabolite, AR-C124910XX, at nine pre-defined time points within the first 6 hours following oral intake of the ticagrelor loading dose. Results: The trial shows no significant differences regarding the pharmacokinetics of ticagrelor between both study arms throughout the study period. AR-C124910XX plasma concentration was significantly higher 120 min after the ticagrelor loading dose administration (p = 0.0417). However, the evaluation of pharmacodynamics did not show any statistically significant differences between the study arms. Conclusions: To conclude, this trial shows that naloxone co-administration in ticagrelor-treated acute coronary syndrome patients on concomitant treatment with morphine shows no definite superiority in terms of ticagrelor pharmacokinetic and pharmacodynamic profile

Early administration of LEvosimendan in Patients witH decompensAted chroNic hearT failure (ELEPHANT) study. Rationale and protocol of the study

Dobutamine and levosimendan are both indicated for inotropic support in acute decompensated heart failure (HF). The study aimed to assess the impact of early administration of levosimendan (first iv therapeutic approach) versus dobutamine (first iv therapeutic approach) on in-hospital treatment expenses and clinical outcomes in patients with decompensated chronic HF. The ELEPHANT study was designed as a phase III, multicentre, randomized 1:1, double-blind, active-controlled trial that will include patients admitted to the hospital due to HF decompensation. Co-primary endpoints were defined as total in-hospital expenses/survivor and duration of hospitalization/survivor. Secondary efficacy endpoints: on the last day of hospitalization: occurrence of treatment side effects, body weight change during hospitalization, BNP change during hospitalization, in-hospital mortality, additional levosimendan administration due to the ineffectiveness of the initial treatment. Patients will be randomized 1:1 to the active group receiving continuous infusion 24 h of levosimendan 0.1 μg/kg/min or to the control group receiving continuous infusion 24 h of dobutamine 3 μg/kg/min. After the enrolment of 20 patients, results analysis will be performed (pilot phase — single centre). Based on this analysis conducted according to the intention-to-treat principle, the final population size will be defined. The multicentre phase of the study will be initiated after the pilot phase

A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study

© 2021 Via Medica. This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license. https://creativecommons.org/licenses/by/4.0/The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome — a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and main-taining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up.Peer reviewedFinal Published versio

Infodemia – an Analysis of Fake News in Polish News Portals and Traditional Media During the Coronavirus Pandemic

The article addresses the issue of the presence of false information on coronavirus in the Polish news media between January and September 2020. The research aimed to check the extent to which traditional media participate in disinformation processes during the pandemic. An attempt has also been made at explaining the reasons for the publication of fake news in these media. Sources of information that Poles use most often were examined: popular information portals, traditional media websites, and social media (Facebook and Twitter). The article analyses false information in both quantitative and qualitative terms. A total of 101 pieces of false information made available online were diagnosed, of which every fourth news item (25.74%) appeared in opinion-forming media (three most popular news portals and all traditional media were taken into account). The qualitative analysis shows that publishing false information in the opinion-forming media is the result of changes in the journalistic work environment (especially declining standards of work, a desire to attract the attention of the media audience and the pursuit of the media organisations’ own interests). However, this issue requires further research in editorial offices and among journalists

Infodemia – an Analysis of Fake News in Polish News Portals and Traditional Media During the Coronavirus Pandemic

The article addresses the issue of the presence of false information on coronavirus in the Polish news media between January and September 2020. The research aimed to check the extent to which traditional media participate in disinformation processes during the pandemic. An attempt has also been made at explaining the reasons for the publication of fake news in these media. Sources of information that Poles use most often were examined: popular information portals, traditional media websites, and social media (Facebook and Twitter). The article analyses false information in both quantitative and qualitative terms. A total of 101 pieces of false information made available online were diagnosed, of which every fourth news item (25.74%) appeared in opinion-forming media (three most popular news portals and all traditional media were taken into account). The qualitative analysis shows that publishing false information in the opinion-forming media is the result of changes in the journalistic work environment (especially declining standards of work, a desire to attract the attention of the media audience and the pursuit of the media organisations’ own interests). However, this issue requires further research in editorial offices and among journalists