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Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Acute Myocardial Infarction (IMPRESSION)

12. august 2017 oppdatert av: Jacek Kubica, Collegium Medicum w Bydgoszczy

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.

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.

Studieoversikt

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

74

Fase

  • Fase 4

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

    • Kujawsko-pomorskie
      • Bydgoszcz, Kujawsko-pomorskie, Polen, 85-094
        • Cardiology Department, Dr. A. Jurasz University Hospital

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 80 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
180 mg ladedose
Andre navn:
  • Brilique
IV bolus injection
Andre navn:
  • Morfinsulfat
Placebo komparator: Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
180 mg ladedose
Andre navn:
  • Brilique
IV bolus injection
Andre navn:
  • Natriumklorid 0,9 %

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)
Tidsramme: 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
Tidsramme: 12 hours
Maximum concentration (Cmax) of ticagrelor
12 hours
Maximum Concentration of AR-C124910XX
Tidsramme: 12 hours
Maximum concentration (Cmax) of AR-C124910XX
12 hours
Time to Maximum Concentration for Ticagrelor
Tidsramme: 12 hours
Time to maximum concentration (Tmax) for ticagrelor
12 hours
Time to Maximum Concentration for AR-C124910XX
Tidsramme: 12 hours
Time to maximum concentration (Tmax) for AR-C124910XX
12 hours
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 12 hours
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
12 hours

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Etterforskere

  • Hovedetterforsker: Prof. Jacek Kubica, MD, PhD, Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. august 2014

Primær fullføring (Faktiske)

1. juni 2015

Studiet fullført (Faktiske)

1. juni 2015

Datoer for studieregistrering

Først innsendt

14. august 2014

Først innsendt som oppfylte QC-kriteriene

14. august 2014

Først lagt ut (Anslag)

15. august 2014

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

12. september 2017

Siste oppdatering sendt inn som oppfylte QC-kriteriene

12. august 2017

Sist bekreftet

1. august 2017

Mer informasjon

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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