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

2017年8月12日 更新者: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.

調査の概要

詳細な説明

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.

研究の種類

介入

入学 (実際)

74

段階

  • フェーズ 4

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

    • Kujawsko-pomorskie
      • Bydgoszcz、Kujawsko-pomorskie、ポーランド、85-094
        • Cardiology Department, Dr. A. Jurasz University Hospital

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年~80年 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

  • 主な目的:処理
  • 割り当て:ランダム化
  • 介入モデル:並列代入
  • マスキング:4倍

武器と介入

参加者グループ / アーム
介入・治療
アクティブコンパレータ:Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
負荷用量 180 mg
他の名前:
  • ブリリック
IV bolus injection
他の名前:
  • 硫酸モルヒネ
プラセボコンパレーター:Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
負荷用量 180 mg
他の名前:
  • ブリリック
IV bolus injection
他の名前:
  • 塩化ナトリウム 0.9%

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
時間枠: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

二次結果の測定

結果測定
メジャーの説明
時間枠
Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)
時間枠: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
時間枠:12 hours
Maximum concentration (Cmax) of ticagrelor
12 hours
Maximum Concentration of AR-C124910XX
時間枠:12 hours
Maximum concentration (Cmax) of AR-C124910XX
12 hours
Time to Maximum Concentration for Ticagrelor
時間枠:12 hours
Time to maximum concentration (Tmax) for ticagrelor
12 hours
Time to Maximum Concentration for AR-C124910XX
時間枠:12 hours
Time to maximum concentration (Tmax) for AR-C124910XX
12 hours
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)
時間枠: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)
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠:12 hours
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
12 hours

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

捜査官

  • 主任研究者:Prof. Jacek Kubica, MD, PhD、Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2014年8月1日

一次修了 (実際)

2015年6月1日

研究の完了 (実際)

2015年6月1日

試験登録日

最初に提出

2014年8月14日

QC基準を満たした最初の提出物

2014年8月14日

最初の投稿 (見積もり)

2014年8月15日

学習記録の更新

投稿された最後の更新 (実際)

2017年9月12日

QC基準を満たした最後の更新が送信されました

2017年8月12日

最終確認日

2017年8月1日

詳しくは

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