E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients undergoing elective coronary artery bypass grafting surgery. |
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E.1.1.1 | Medical condition in easily understood language |
Patients undergoing elective coronary artery bypass grafting surggery. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059489 |
E.1.2 | Term | Hemodilution |
E.1.2 | System Organ Class | 100000004863 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068176 |
E.1.2 | Term | Coronary artery bypass graft |
E.1.2 | System Organ Class | 100000004865 |
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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 |
The aim of this study is to compare 6% hydroxyethyl starch (HES) 130/0.4 in a balanced electrolyte solution (Volulyte®) with modified fluid gelatin (Geloplasma®) as the priming solution for the cardiopulmonary bypass (CPB) circuit. |
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E.2.2 | Secondary objectives of the trial |
The microvascular reactivity and the effects on tissue (StO2) and cerebral (ScO2) oxygen saturation will be examined using near-infrared spectroscopy (NIRS). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult consenting patients scheduled for elective coronary artery bypass grafting surgery on moderately hypothermic (> 32°C) CPB without blood transfusion will be recruited. Age ≥ 18 years. |
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E.4 | Principal exclusion criteria |
Exclusion criteria are an ejection fraction < 25%, a known allergy to HES, admission of HES or gelatines within the preceding 2 weeks, renal insufficiency (creatinine > 2.0 mg/dl), significant hepatic disease (liver function tests > 3x upper limit of normal), history of cerebrovascular disease, significant carotid artery stenosis (> 60%), perioperative use of corticosteroids, and need for vasopressor or inotropic therapy before surgery. An expected haematocrit on CPB, calculated based on preoperative haematocrit, calculated blood volume and amount of cardioplegia, of < 23% is also considered an exclusion criterium (Ranucci 2006). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Endpoints are the effect of the priming solution on microvascular reactivity measured with NIRS. Oxygen consumption, recovery times and resaturation rate will be determined. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
ScO2 and StO2 will be recorded continuously. Microvascular reactivity will be measured at the following time moments: awake (T0), after induction (T1), just after sternotomy (T2), just after heparinization (T3), 5 (T4) and 30 minutes after aortic cross-clamping (T5), 10 minutes after administration of protamin (T6), at skin closure (T7), and 2 hours after arrival at intensive care (T8). |
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E.5.2 | Secondary end point(s) |
secondary parameters are continuous measurements of ScO2 and StO2 , blood gases (haemoglobin, arterial and venous oxygen content (CaO2 and CvO2), PavCO2 difference, pH, base excess, bicarbonate and lactate) at the different time moments, and continuous registration of haemodynamic parameters, urinary output and use of vasoactive medication during CPB. Postoperative creatinin at arrival on ICU will also be noted. Systemic oxygen delivery (DO2) and oxygen extraction ratio (OER) will be calculated according to standard formulae. Arterial (venous) oxygen content: Ca(v)O2 = 1.34 * Hb * Sa(v)O2 + 0.003 * Pa(v)O2, where Hb = haemoglobin concentration, Sa(v)O2 = arterial (venous) oxygen saturation, Pa(v)O2 = arterial (venous) partial pressure of oxygen. DO2 = Q * CaO2, where Q = pump flow. OER = (CaO2 - CvO2)/CaO2. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Until after patient arrival at ICU. |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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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Until patient arrival at ICU. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |