A Randomized, Double-blind Study Evaluating the Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor and Its Active Metabolite (AR-C124910XX) in Patients With ST-segment Elevation Myocardial Infarction and Non-ST-segment Elevation Myocardial Infarction.
Overview
- Phase
- Phase 4
- Intervention
- Morphine
- Conditions
- ST-segment Elevation Myocardial Infarction
- Sponsor
- Collegium Medicum w Bydgoszczy
- Enrollment
- 74
- Locations
- 1
- Primary Endpoint
- Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of the IMPRESSION study is to determine whether intravenous administration of morphine prior to ticagrelor administration in ST-segment elevation myocardial infarction (STEMI) patients and in non-ST-segment elevation myocardial infarction (NSTEMI) patients alters the plasma concentrations of ticagrelor and its active metabolite and whether it is associated with any negative impact on the antiplatelet effect of ticagrelor.
Detailed Description
The European Society of Cardiology and American Heart Association guidelines recommend use of morphine as a treatment of choice for pain relief in STEMI patients. However, this recommendation, although strong, is only based on expert consensus (class of recommendation I, level of evidence C). Morphine, apart from its analgesic effects, also alleviates the work of breathing and reduces anxiety. On the other hand, despite its favorable analgesic and sedative actions, morphine also exerts adverse effects, which include hypotension, bradycardia, respiratory depression, vomiting and reduction of gastrointestinal motility. Some of the previously listed morphine's side effects could affect the intestinal absorption and thus pharmacokinetics and pharmacodynamics of orally administered drugs which are concomitantly used with morphine. At present, no pharmacokinetic and pharmacodynamic data regarding the concurrent use of morphine and P2Y12 blockers in the STEMI or NSTEMI setting are available. Therefore, evidence-based verification of morphine's influence on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) could provide a valuable insight in the knowledge regarding modern acute myocardial infarction management. Predefined subanalysis: aimed to investigate which one of platelet reactivity assessment methods utilized in the study (VASP assay, MEA, LTA, VerifyNow) best reflects concentration of ticagrelor and its active metabolite (AR-C124910XX). Since there is no reference study examining pharmacokinetics of ticagrelor in STEMI or NSTEMI patients, we decided to perform an internal pilot study of approximately 30 patients (15 patients for each arm) for estimating the final sample size.
Investigators
Jacek Kubica
Prof. dr hab.
Collegium Medicum w Bydgoszczy
Eligibility Criteria
Inclusion Criteria
- •provision of informed consent prior to any study specific procedures
- •diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment elevation myocardial infarction
- •male or non-pregnant female, aged 18-80 years old
- •provision of informed consent for angiography and PCI
Exclusion Criteria
- •chest pain described by the patient as unbearable or patient's request for analgesics
- •prior morphine administration during the current STEMI or NSTEMI
- •treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment
- •hypersensitivity to ticagrelor
- •current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin
- •active bleeding
- •history of intracranial hemorrhage
- •recent gastrointestinal bleeding (within 30 days)
- •history of coagulation disorders
- •platelet count less than \<100 x10\^3/mcl
Arms & Interventions
Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
Intervention: Morphine
Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
Intervention: Ticagrelor
Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
Intervention: Placebo
Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
Intervention: Ticagrelor
Outcomes
Primary Outcomes
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
Time Frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose
Secondary Outcomes
- Time to Maximum Concentration for AR-C124910XX(12 hours)
- Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA(2 hours)
- Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP(12 hours)
- Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA(12 hours)
- Maximum Concentration of Ticagrelor(12 hours)
- Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)(prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose)
- Maximum Concentration of AR-C124910XX(12 hours)
- Time to Maximum Concentration for Ticagrelor(12 hours)
- Platelet Reactivity Index Assessed by VASP Assay(12 hours post ticagrelor dose)
- P2Y12 Reaction Units Assessed by VerifyNow(12 hours post ticagrelor dose)
- Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)(prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose)
- Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6)(prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose)
- Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry(12 hours post ticagrelor dose)
- Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP(2 hours)
- Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow(2 hours)
- Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow(12 hours)