E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Antithrombotic therapy after surgical replacement of stenotic heart valve by a bioprosthesis or mitral valve repair |
Patienten nach chirurgischem Ersatz einer Aortenklappe mit einer Bioprothese oder nach Mitralklappenrekonstruktion benötigen eine wirksame antithrombotische Therapie mit Acetylsalicylsäure (ASS 100mg/Tag). ASS wird ab dem ersten postoperativen Tag verabreicht. Trotzdem zeigen über 50% der Patienten eine unzureichende Wirkung von ASS (high on-treatment platelet reactivity - HTPR). Diese Problematik kann durch die Einnahme von Nichtopioidanalgetika noch verstärkt werden. |
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E.1.1.1 | Medical condition in easily understood language |
Impact of concomitant treatment with analgesic drugs on antiplatelet effect of aspirin in patients early after surgical replacement of the aortic valve by a bioprosthesis or mitral valve repair |
Einfluss von Schmerzmitteln auf die Blutplättchenhemmende Wirkung von ASS in der frühen Phase nach chirurgischem Ersatz einer Aortenherzklappe mit einer Bioprothese oder Mitralklappenrekonstruktion. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Comparative assessment of the impact of concomitant treatment with the analgesic drugs dipyrone (metamizole) versus paracetamol on the antiplatelet effect of low-dose aspirin in the early postoperative period after surgical replacement of the stenotic aortic valve by a bioprosthesis or surgical mitral valve repair |
Postoperativer thrombozytenhemmender Effekt von Acetylsalicylsäure bei herzchirurgischen Patienten: Einfluss von Metamizol |
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E.2.2 | Secondary objectives of the trial |
- Proportion of patients with an adequate antiplatelet response to low dose aspirin by thromboxane B2 assay at day 2 after surgical replacement of the stenotic aortic valve by a bioprosthesis or surgical mitral valve repair
- Assessment of platelet reactivity by use of other laboratory assays respective different stimulants.
- Immature platelet fraction and immature platelet count
- hsCRP and IL-6 in plasma/serum |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Clinical indication for surgical replacement of the stenotic aortic valve by a bioprosthesis without concomitant CABG or surgical mitral valve repair
- Age > 50years
- Written informed consent
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E.4 | Principal exclusion criteria |
- Re-do heart surgery
- Indication for oral anticoagulation
- Known disorders of coagulation
- Chronic hepatic disease
- Chronic alcohol abuse
- Known malnutrition status
- Creatine clearance <30 ml7Min (CKD-EPI-formula)
- End-stage renal disease requring hemodialysis
- Known hematological disorders
- Peri-or postoperative transfusion of platelets
- Treatment with aspirin within 10 days prior to surgery
- Positive result in pregnancy in urine testing in female pre-menopausal patients
- Participation in any interventional study according to German Drug Law (AMG) or Medicinal Device Law (MPG) within 30 days before enrollment in this study
- Known hypersensitivity to dipyrone (metamizole) or paracetamol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with an adequate antiplatelet response to low dose aspirin (100 mg/day) at day 4/5 after surgical replacement of the stenotic aortic valve by a bioprosthesis or surgical mitral valve repair. Adequate response to aspirin is assessed by determination of thromboxane B2 after stimulation of platelet rich plasma with arachidonic acid |
Patientenanteil mit ausreichender ASS-Wirkung (ASS-Responder) beurteilt anhand der Thromboxan-Bildung in vitro im plättchenreichen Plasma nach Stimulation mit Arachidonsäure. Eine erhöhte Plättchenreaktivität unter ASS (Non-Responderstatus) wird anhand der Messung von Thromboxan B2 nach Stimulation mit Arachidonsäure am Tag 4/5 nach Implantation einer biologischen Aortenklappe oder chirurgischer Reparatur der Mitralklappe (Mitralklappenrekonstruktion) beurteilt |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 4/5 after surgical replacement of the aortic valve or surgical mitral valve repair |
Tag 4/5 nach herzchirurgischem Ersatz der Aortenklappe mit einer Bioprothese oder chirurgischer Reparatur der Mitralklappe (Mitralklappenrekonstruktion) |
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E.5.2 | Secondary end point(s) |
- Proportion of patients with an adequate antiplatelet response to low dose aspirin by thromboxane B2 assay at day 2 after surgical replacement of the stenotic aortic valve by a bioprosthesis or mitral valve repair. Adequate response to aspirin is assessed by determination of thromboxane B2 after stimulation of platelet rich plasma with arachidonic acid
Assessment of platelet reactivity by other laboratory assays respective different stimulants.
- Platelet reactivity by light transmission aggregometry after stimulation of platelet rich plasma with arachidonic acid 200 mg/L
- Platelet reactivity by Multiple Electrode Impedance Aggregometry after stimulation of hirudine anticoagulated blood with arachidonic acid (ASPItest)
- Platelet reactivity by light transmission aggregometry after stimulation of platelet rich plasma with thrombin receptor activating peptide (TRAP)
- Platelet reactivity by Multiple Electrode Impedance Aggregometry after stimulation of hirudine anticoagulated blood with thrombin receptor activating peptide (TRAPtest)
- Platelet reactivity by light transmission aggregometry after ex vivo incubation with different concentrations of aspirin and stimulation with arachidonic acid (500 mg/L)
- Immature platelet fraction and immature platelet count
- hsCRP and IL-6 in plasma/serum |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Days 1, 2 respective 4/5 after surgical replacement of the aortic valve or surgical mitral valve repair |
Tag 1, 2 bzw. 4/5 nach chirurgischem Ersatz der Aortenklappe oder chirurgischer Reparatur der Mitralklappe (Mitralklappenrekonstruktion) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of last patient |
Letzte Visite beim letzten eingeschlossenen Patienten |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |