Effects of Intracoronary Progenitor Cell Therapy on Coronary Flow Reserve After Acute MI (REPAIR-ACS)
Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute Coronary Syndrome: REPAIR - ACS
Coronary flow reserve is an important measure of the integrity of the coronary microcirculation. Moreover, impaired coronary flow reserve is a predictor of future cardiovascular events and poor prognosis in patients after acute myocardial infarction.
After acute myocardial infarction, coronary flow reserve remains significantly reduced. A previous randomized, double-blind Placebo-controlled trial (REPAIR-AMI) demonstrated complete normalization of coronary flow reserve after intracoronary application of autologous bone marrow-derived progenitor cells (but no effect in the placebo group) in patients with ST segment elevation myocardial infarction. The current study is planned to extend these findings to patients with Non-ST segment elevation myocardial infarction, since these patients have an equally reduced outcome.
調査の概要
状態
詳細な説明
Improvement of neovascularization is a key mechanism of functional improvement of intracoronary application of progenitor cells after acute myocardial infarction. Since capillary density cannot be assessed histological in patients, measurement of coronary flow reserve is an exact means for estimating capillary density and assessing coronary microvascular function. With the help of an intracoronary Doppler Wire, coronary hemodynamics can be assessed at baseline and, for example, adenosin-induced maximal vasodilation. Calculation of the minimal vascular resistance indices allows to estimate the cross-sectional area, reflecting capillary density, and, in comparison with the time of the acute myocardial infarction, estimation of improved neovascularization at a later timepoint.
In order to improve neovascularization, which may then be associated with improved left ventricular contractility, we initiated the current trial.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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Frankfurt、ドイツ、60590
- Med. Klinik III; Kardiologie
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Leipzig、ドイツ、04289
- Universität Leipzig / Herzzentrum
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
Patients with acute coronary syndrome (ST-depression in at least 2 leads > 0,1 mV), or T-wave inversion, with or without elevated myocardial biomarkers (Troponin T oder I), together with typical clinical presentation), treated as follows:
- Acute percutaneous revascularization with stent implantation within 48 hours after symptom onset.
- Successful acute PCI (residual stenosis < 30%, TIMI flow > 2).
- Hemodynamic stability
- Age 18 - 80 years
- Written informed consent
- Active contraception in women of childbearing age
Exclusion Criteria:
- Patients with STEMI (ST elevation in 2 leads above 0,2 mV in lead V1, V2 oder V3 or above 0,1 mV in the other leads)
- Necessity of additional PCI in non-infarct vessel at the time of study therapy (multi-vessel PCI in the acute event is possible)
- Heart failure (LVEF ≤ 30 %).
- Arteriovenous malformation or aneurysms
- Active infection (C-reactive protein > 10 mg/dl), or fever, or diarrhoea within the last 4 weeks
- Chronic inflammatory disease
- HIV infection or active hepatitis
- Neoplastic disease without documented complete remission within the last 5 years
- Recent stroke within the last 3 months
- Impaired kidney function (creatinin > 2,5 mg/dl) at the time of treatment
- Significant liver disease (GOT > 2x upper normal value or spontaneous INR > 1,5.
- Hematopoetic disease (anaemia with Hb< 8.5 mg/dl; thrombocytopenia < 100.000/µl; splenomegaly
- Known allergies to Clopidogrel, Heparin or Abciximab
- History of bleeding disorder
- GI bleeding within the last 3 months
- Major surgery or trauma within the last 2 months
- Uncontrolled hypertension
- Pregnancy
- Mental disability
- Previous progenitor cell therapy
- Participation in a different clinical trial within the last 30 days
研究計画
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 |
|---|---|
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アクティブコンパレータ:1
Intracoronary infusion of autologous bone marrow-derived progenitor cells after NSTEMI
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intracoronary infusion of autologous bone marrow-derived progenitor cells isolated from 50 ml bone marrow aspirate
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プラセボコンパレーター:2
Intracoronary infusion of Placebo after NSTEMI
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intracoronary infusion of placebo medium
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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 |
時間枠 |
|---|---|
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Improvement of coronary flow reserve in the infarct vessel
時間枠:4 months
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4 months
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Improvement of relative coronary flow reserve
時間枠:4 months
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4 months
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Improvement of global and regional left ventricular ejection fraction
時間枠:4 months
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4 months
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Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization)
時間枠:4 months
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4 months
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Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization)
時間枠:12 months
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12 months
|
協力者と研究者
捜査官
- 主任研究者:Andreas M Zeiher, MD、Goethe University
出版物と役立つリンク
一般刊行物
- Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation. 2002 Dec 10;106(24):3009-17. doi: 10.1161/01.cir.0000043246.74879.cd.
- Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM; REPAIR-AMI Investigators. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006 Sep 21;355(12):1210-21. doi: 10.1056/NEJMoa060186.
- Dimmeler S, Burchfield J, Zeiher AM. Cell-based therapy of myocardial infarction. Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):208-16. doi: 10.1161/ATVBAHA.107.155317. Epub 2007 Oct 19.
- Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Werner N, Haase J, Neuzner J, Germing A, Mark B, Assmus B, Tonn T, Dimmeler S, Zeiher AM; REPAIR-AMI Investigators. Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J. 2006 Dec;27(23):2775-83. doi: 10.1093/eurheartj/ehl388. Epub 2006 Nov 10.
- Erbs S, Linke A, Schachinger V, Assmus B, Thiele H, Diederich KW, Hoffmann C, Dimmeler S, Tonn T, Hambrecht R, Zeiher AM, Schuler G. Restoration of microvascular function in the infarct-related artery by intracoronary transplantation of bone marrow progenitor cells in patients with acute myocardial infarction: the Doppler Substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial. Circulation. 2007 Jul 24;116(4):366-74. doi: 10.1161/CIRCULATIONAHA.106.671545. Epub 2007 Jul 9.
- Schachinger V, Assmus B, Honold J, Lehmann R, Hofmann WK, Martin H, Dimmeler S, Zeiher AM. Normalization of coronary blood flow in the infarct-related artery after intracoronary progenitor cell therapy: intracoronary Doppler substudy of the TOPCARE-AMI trial. Clin Res Cardiol. 2006 Jan;95(1):13-22. doi: 10.1007/s00392-006-0314-x.
- Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol. 2004 Oct 19;44(8):1690-9. doi: 10.1016/j.jacc.2004.08.014.
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
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最終確認日
詳しくは
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