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Compare Ticagrelor vs Clopidogrel on the Reduction of Arterial Stiffness and Wave Reflectionsin Patients With CAD. (NOVELTY)

2019年6月18日 更新者:Hellenic Cardiovascular Research Society

A Single Center Phase II Assessor-Blinded RaNdomised Active Controlled Parallel-Group Trial to COmpare Ticagrelor Versus Clopidogrel on the REduction of ArteriaL STiffness and Wave Reflections in Patients With CoronarY Artery Disease.

The purpose of this study is to investigate the potential acute and chronic effect of ticagrelor versus clopidogrel on arterial stiffness and other vascular risk markers of interest, the study will consist of two periods: a 24-hour ACUTE period where 60 subjects with an indication for coronary angiography (CA) with or without percutaneous coronary intervention (PCI) will be included, and a 30-day CHRONIC period where approximately 60 subjects that will undergo PCI will be included and studied (refer to Section 3 'Study Plan and Procedures'). The primary objective of this study is to compare ticagrelor versus clopidogrel regarding their effect on arterial stiffness as assessed by PWV, at 3 hours after the loading dose of each regimen, in eligible subjects with CAD.

調査の概要

状態

完了

介入・治療

詳細な説明

This is singe-center, randomized, assessor-blinded, active controlled, parallel-group trial consisting of an 'acute' and a 'chronic' period, aiming at comparing ticagrelor versus clopidogrel on the reduction of arterial stiffness and wave reflections in patients with CAD. This Investigator-Sponsored Study (ISS) will be supported by AstraZeneca.

60 subjects fulfilling all study-specific eligibility criteria will be initially recruited for the 'acute' study period of 24-hour duration. Subjects that will undergo ad hoc PCI will continue in the subsequent 'chronic' study period of 30-day duration.

In order to have 60 subjects in the 'chronic' study period (since some of the 'acute' period will not undergo PCI), additional subjects that are scheduled for elective PCI will be recruited until the sample size of 'chronic' study period reaches 60 subjects.

The study periods [Figure 1, Flow Chart] have as follows:

For the 24-hour ACUTE period, 60 subjects with an indication for elective CA with or without PCI will be included in the study.

Three (3) hours before the CA the subjects will be randomized in the two study treatment arms:

Ticagrelor arm: 30 subjects will receive

  • 180 mg loading dose of ticagrelor,
  • 1st maintenance ticagrelor dose of 90 mg at 12 hours. Clopidogrel arm: 30 subjects will receive
  • 600 mg loading dose of clopidogrel.

Study measurements (arterial stiffness, central blood pressure and endothelial function) for both study treatment arms will be performed at:

  • baseline (0 hours - prior to the loading dose administration)
  • 3 hours (after the loading dose of each regimen and before CA), and at
  • 24 hours (before the administration of the 2nd maintenance dose of ticagrelor and the 1st maintenance dose of clopidogrel).

For the 30-day CHRONIC period, 60 subjects that will undergo PCI (stent implantation) will be studied. Part of this 'chronic' period population will consist of the subjects that were included in the 'acute' period and proceeded ad hoc to PCI. The remainder will be subjects being scheduled for elective PCI, who will be enrolled after the completion of the recruitment in the 'acute' study period.

Approximately 30 subjects will be allocated to ticagrelor loading dose and maintenance dose (90 mg BID) thereafter and approximately 30 subjects will be allocated to 600 mg of clopidogrel and maintenance dose (75 mg QD) thereafter.

Study measurements for the subjects of the 'acute' period that will enter the 'chronic' period will be performed at:

- 30 days post-PCI (prior to the administration of the morning maintenance dose of the assigned treatment regimen at the day of study visit).

Study measurements for the additional subjects with indication of elective PCI that will be enrolled directly into the chronic study period will be performed at:

  • baseline (0 hours - prior to the administration of the loading dose of each treatment regimen and 3 hours before the PCI)
  • 30 days post PCI (prior to the administration of the morning maintenance dose of the assigned treatment regimen at the day of study visit).

All study-related procedures will be carried out in accordance with the institutional guidelines and common practice.

研究の種類

介入

入学 (実際)

120

段階

  • フェーズ2

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

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~79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:

  1. Provision of informed consent prior to any study specific procedures.
  2. Male and female subjects > 18 and < 79 years of age.
  3. Indication for elective coronary angiography (angina, positive stress test/SPECT/stress echo) with or without PCI for inclusion in the 'acute' study period, and indication for either ad hoc or elective PCI for inclusion in the 'chronic' study period.

Exclusion Criteria:

  1. Who had ACS within 12 months of screening.
  2. Previous stent implantation with dual antiplatelet therapy within 12 months of screening.
  3. Subjects being treated with anti-platelet medications other than aspirin prior to diagnostic catheterization including glycoprotein IIb/IIIa inhibitors.
  4. Subjects with NYHA class III or IV heart failure or known left ventricular ejection fraction < 30%.
  5. Subjects with hemodynamic or electrical instability (including shock).
  6. History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 6 months.
  7. Other bleeding diathesis, or considered by Investigator to be at high risk for bleeding.
  8. Any previous history of ischemic or hemorrhagic stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm).
  9. International Normalized Ratio (INR) known to be >1.5 within 1 week of study entry.
  10. Poorly controlled blood pressure (>160/100 mmHg).
  11. Known platelet count of <100,000/mm3 within 1 week of study entry.
  12. Known anemia (hemoglobin [Hb] <10 gr/dL) within 1 week of study entry.
  13. Subjects receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study.
  14. Severe kidney disease (GFR<30 ml/min/1.73m2).
  15. Hepatic insufficiency defined as liver cirrhosis, AST/ALT/Alkaline Phosphatase greater than 3 times the upper limit of normal or hyperbilirubinemia defined as peak total serum bilirubin greater than 2 times the upper limit of normal (ULN).
  16. Any indication (atrial fibrillation, mitral stenosis or prosthetic heart valve, pulmonary embolism (PE), deep vein thrombosis (DVT)) for anticoagulation treatment during study period.
  17. Asthma or chronic obstructive pulmonary disease requiring brochodilating agents.
  18. Concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inhibitors (atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole) or inducers (carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, and rifapentine).
  19. Concomitant use of drugs that are metabolized through CYP2C19 (omeprazole and esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine and chloramphenicol).
  20. History of uric acid nephropathy and high levels of uric acid within 1 week of study entry.
  21. Increased risk of bradycardic events (e.g. known sick sinus syndrome or third degree AV block or previous documented syncope suspected to be due to bradycardia unless treated with a pacemaker).
  22. Known neoplastic or autoimmune disease or any concomitant medical illness that in the opinion of the Investigator may interfere with or prevent completion in this study.
  23. Contraindication to clopidogrel, ASA, or ticagrelor.
  24. A history of alcohol and/or substance abuse that could interfere with conduct of the trial.
  25. Pregnancy or lactation (for premenopausal women 2 methods of reliable contraception, one of which must be barrier method, are required).
  26. Treatment with other investigational agents (including placebo) or devices within 30 days prior to randomization or planned use of investigational agents or devices prior to the Day 30 visit.
  27. Life expectancy less than 1 year.
  28. Indication for major surgery (e.g. cancer treatment, carotid surgery, cerebral surgery, major vascular surgery).
  29. High likelihood of being unavailable for the Day 30 follow up.

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:独身

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:Clopidogrel
Loading dose 600 mg .Mainatinance dose 75 mg QD
Loading dose 180 mg . Maintainance dose 90 mg BID
他の名前:
  • ブリリーク
実験的:Ticagrelor
Loading dose 180 mg . Maintenance 90 mg BID
Loading dose 180 mg . Maintainance dose 90 mg BID
他の名前:
  • ブリリーク

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
Mean Change in the cfPWV
時間枠:at 3 hours after the loading dose
The primary outcome is the treatment difference in the mean change in cfPWV from baseline (0 hours) at 3 hours after the loading dose of each regimen, in ticagrelor and clopidogrel acute period populations.
at 3 hours after the loading dose

二次結果の測定

結果測定
メジャーの説明
時間枠
mean change in the cfPWV
時間枠:from baseline at 24 hours after the loading dose
The treatment difference in the mean change in the cfPWV from baseline (0 hours) at 24 hours after the loading dose of each regimen, in the acute period populations;
from baseline at 24 hours after the loading dose

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。

協力者

捜査官

  • 主任研究者:Charalambos Vlachopoulos、Ippokratio Hospital Athens , Greece

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2月1日

一次修了 (実際)

2018年6月1日

研究の完了 (実際)

2018年6月1日

試験登録日

最初に提出

2014年2月21日

QC基準を満たした最初の提出物

2014年2月24日

最初の投稿 (見積もり)

2014年2月25日

学習記録の更新

投稿された最後の更新 (実際)

2019年6月19日

QC基準を満たした最後の更新が送信されました

2019年6月18日

最終確認日

2019年6月1日

詳しくは

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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