- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT02217878
Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Acute Myocardial Infarction (IMPRESSION)
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.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 4
Kontakter och platser
Studieorter
-
-
Kujawsko-pomorskie
-
Bydgoszcz, Kujawsko-pomorskie, Polen, 85-094
- Cardiology Department, Dr. A. Jurasz University Hospital
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
- hemoglobin concentration less than 10.0 g/dl
- history of moderate or severe hepatic impairment
- history of major surgery or severe trauma (within 3 months)
- patients considered by the investigator to be at risk of bradycardic events
- second or third degree atrioventricular block during screening for eligibility
- history of asthma or severe chronic obstructive pulmonary disease
- patient required dialysis
- manifest infection or inflammatory state
- Killip class III or IV during screening for eligibility
- respiratory failure
- history of severe chronic heart failure (NYHA class III or IV)
- concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment
- body weight below 50 kg
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Fyrdubbla
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Aktiv komparator: Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
|
180 mg laddningsdos
Andra namn:
IV bolus injection
Andra namn:
|
|
Placebo-jämförare: Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
|
180 mg laddningsdos
Andra namn:
IV bolus injection
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
Tidsram: 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
|
prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)
Tidsram: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
|
Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose
|
prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
|
|
Maximum Concentration of Ticagrelor
Tidsram: 12 hours
|
Maximum concentration (Cmax) of ticagrelor
|
12 hours
|
|
Maximum Concentration of AR-C124910XX
Tidsram: 12 hours
|
Maximum concentration (Cmax) of AR-C124910XX
|
12 hours
|
|
Time to Maximum Concentration for Ticagrelor
Tidsram: 12 hours
|
Time to maximum concentration (Tmax) for ticagrelor
|
12 hours
|
|
Time to Maximum Concentration for AR-C124910XX
Tidsram: 12 hours
|
Time to maximum concentration (Tmax) for AR-C124910XX
|
12 hours
|
|
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)
Tidsram: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
|
Exposure to ticagrelor during the first 6 hours after ticagrelor loading dose
|
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)
Tidsram: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
|
Exposure to ticagrelor metabolite during the first 6 hours after ticagrelor loading dose
|
prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
|
|
Platelet Reactivity Index Assessed by VASP Assay
Tidsram: prior to the initial ticagrelor dose
|
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
|
prior to the initial ticagrelor dose
|
|
Platelet Reactivity Index Assessed by VASP Assay
Tidsram: 30 minutes post ticagrelor dose
|
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
|
30 minutes post ticagrelor dose
|
|
Platelet Reactivity Index Assessed by VASP Assay
Tidsram: 1 hour post ticagrelor dose
|
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
|
1 hour post ticagrelor dose
|
|
Platelet Reactivity Index Assessed by VASP Assay
Tidsram: 2 hours post ticagrelor dose
|
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
|
2 hours post ticagrelor dose
|
|
Platelet Reactivity Index Assessed by VASP Assay
Tidsram: 3 hours post ticagrelor dose
|
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
|
3 hours post ticagrelor dose
|
|
Platelet Reactivity Index Assessed by VASP Assay
Tidsram: 4 hours post ticagrelor dose
|
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
|
4 hours post ticagrelor dose
|
|
Platelet Reactivity Index Assessed by VASP Assay
Tidsram: 6 hours post ticagrelor dose
|
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
|
6 hours post ticagrelor dose
|
|
Platelet Reactivity Index Assessed by VASP Assay
Tidsram: 12 hours post ticagrelor dose
|
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
|
12 hours post ticagrelor dose
|
|
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Tidsram: prior to the initial ticagrelor dose
|
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
|
prior to the initial ticagrelor dose
|
|
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Tidsram: 30 minutes post ticagrelor dose
|
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
|
30 minutes post ticagrelor dose
|
|
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Tidsram: 1 hour post ticagrelor dose
|
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
|
1 hour post ticagrelor dose
|
|
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Tidsram: 2 hours post ticagrelor dose
|
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
|
2 hours post ticagrelor dose
|
|
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Tidsram: 3 hours post ticagrelor dose
|
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
|
3 hours post ticagrelor dose
|
|
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Tidsram: 4 hours post ticagrelor dose
|
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
|
4 hours post ticagrelor dose
|
|
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Tidsram: 6 hours post ticagrelor dose
|
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
|
6 hours post ticagrelor dose
|
|
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Tidsram: 12 hours post ticagrelor dose
|
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
|
12 hours post ticagrelor dose
|
|
P2Y12 Reaction Units Assessed by VerifyNow
Tidsram: prior to the initial ticagrelor dose
|
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
|
prior to the initial ticagrelor dose
|
|
P2Y12 Reaction Units Assessed by VerifyNow
Tidsram: 30 minutes post ticagrelor dose
|
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
|
30 minutes post ticagrelor dose
|
|
P2Y12 Reaction Units Assessed by VerifyNow
Tidsram: 1 hour post ticagrelor dose
|
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
|
1 hour post ticagrelor dose
|
|
P2Y12 Reaction Units Assessed by VerifyNow
Tidsram: 2 hours post ticagrelor dose
|
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
|
2 hours post ticagrelor dose
|
|
P2Y12 Reaction Units Assessed by VerifyNow
Tidsram: 3 hours post ticagrelor dose
|
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
|
3 hours post ticagrelor dose
|
|
P2Y12 Reaction Units Assessed by VerifyNow
Tidsram: 4 hours post ticagrelor dose
|
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
|
4 hours post ticagrelor dose
|
|
P2Y12 Reaction Units Assessed by VerifyNow
Tidsram: 6 hours post ticagrelor dose
|
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
|
6 hours post ticagrelor dose
|
|
P2Y12 Reaction Units Assessed by VerifyNow
Tidsram: 12 hours post ticagrelor dose
|
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
|
12 hours post ticagrelor dose
|
|
Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP
Tidsram: 2 hours
|
Percentage of Patients With High Platelet Reactivity (HPR) 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 MEA
Tidsram: 2 hours
|
Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA
|
2 hours
|
|
Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow
Tidsram: 2 hours
|
Percentage of Patients With High Platelet Reactivity (HPR) 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 VASP
Tidsram: 12 hours
|
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP
|
12 hours
|
|
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA
Tidsram: 12 hours
|
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA
|
12 hours
|
|
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow
Tidsram: 12 hours
|
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
|
12 hours
|
Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: Prof. Jacek Kubica, MD, PhD, Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu
Publikationer och användbara länkar
Allmänna publikationer
- Kubica J, Adamski P, Ostrowska M, Sikora J, Kubica JM, Sroka WD, Stankowska K, Buszko K, Navarese EP, Jilma B, Siller-Matula JM, Marszall MP, Rosc D, Kozinski M. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016 Jan 14;37(3):245-52. doi: 10.1093/eurheartj/ehv547. Epub 2015 Oct 21.
- Kubica J, Adamski P, Ostrowska M, Kozinski M, Obonska K, Laskowska E, Obonska E, Grzesk G, Winiarski P, Paciorek P. Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients with Acute Myocardial Infarction (IMPRESSION): study protocol for a randomized controlled trial. Trials. 2015 Apr 29;16:198. doi: 10.1186/s13063-015-0724-z.
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Ischemi
- Patologiska processer
- Nekros
- Myokardischemi
- Hjärtsjukdom
- Hjärt-kärlsjukdomar
- Kärlsjukdomar
- Hjärtinfarkt
- Infarkt
- ST Elevation hjärtinfarkt
- Läkemedels fysiologiska effekter
- Neurotransmittormedel
- Molekylära mekanismer för farmakologisk verkan
- Depressiva medel i centrala nervsystemet
- Agenter från det perifera nervsystemet
- Analgetika
- Sensoriska systemagenter
- Trombocytaggregationshämmare
- Purinerga P2Y-receptorantagonister
- Purinerga P2-receptorantagonister
- Purinerga antagonister
- Purinerga medel
- Analgetika, Opioid
- Narkotika
- Ticagrelor
- Morfin
Andra studie-ID-nummer
- CMUMK202
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
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