E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Evaluation of the effect of 80% versus 30% supplemental oxygen administration during major abdominal surgery on postoperative brain natriuretic peptide concentration.
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E.1.1.1 | Medical condition in easily understood language |
The effect of oxygen on heart function.
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059883 |
E.1.2 | Term | Fraction of inspired oxygen |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050322 |
E.1.2 | Term | Oxygen supplementation |
E.1.2 | System Organ Class | 100000173317 |
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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 |
Due to the significant reduction of BNP by inhibiting sympathic nerve activity we hypothesize that supplemental oxygen have beneficial effects in perioperative BNP release in cardiac risk patients undergoing major abdominal surgery. |
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E.2.2 | Secondary objectives of the trial |
1) Effect of supplemental oxygen on postoperative troponin T concentration. 2) Influence of supplemental oxygen on perioperative plasma catecholamine concentration. 3) The effect of oxygen on the redox potential. 4) The effect of hyperoxia on needed vasopressor for hemodynamic stability due to enhanced vasoconstriction 5) Endothelial release of vWF in order to evaluate the endothelial response to supplemental oxygen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients over 45 years on age, which fulfill 1 or more of the following 4 criteria undergoing non-cardiac surgery: 1. History of coronary artery disease 2. History of peripheral arterial disease 3. History of stroke OR 4. Any of 3 of 7 A) Age ≥ 70 years B) Undergoing major surgery C) History of congestive heart failure D) History of transient ischemic attack E) Diabetes and currently taking an oral hypoglycemic agent or insulin F) History of Hypertension
Further inclusion criteria are: 1. Written informed consent 2. Elective major abdominal open surgery or laparoscopically assisted procedures scheduled to take over two hours done under general anesthesia (colorectal, urology, gynecology, liver and pancreatic surgery) |
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E.4 | Principal exclusion criteria |
1. Symptoms of infection or sepsis 2. Preoperative inotropic therapy 3. Patients under ICU treatment 4. Oxygen dependent patients 5. History of severe heart failure and/or EF < 30% |
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E.5 End points |
E.5.1 | Primary end point(s) |
Supplemental oxygen leads to a significant reduction of BNP in patients suffering congestive heart failure due to inhibiting of sympathic nerve activity. In the following trial, we want to evaluate the effect of supplemental intraoperative oxygen in cardiac risk patients undergoing major surgery. Our primary outcome parameter will be the perioperative brain natriuretic peptide. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Brain natriuretic peptide measurement will be performed within 2 hours after end of surgery, on postoperative day 1, 3 and before discharge but at least within 72hours. |
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E.5.2 | Secondary end point(s) |
1) Harmful effects of hyperoxia were described in patients suffering acute myocardial syndrome, however almost no data exists about patients in the perioperative setting without an acute myocardial event. Myocardial injury after noncardiac surgery (MINS) is associated with significant increased 30-day mortality. Patients with a troponin T level > 0.04ng/l will be assessed for ischemic features. 2) All participants will be monitored for cardiac morbidity as there are: a) myocardial infarction requiring medical intervention, b) acute heart failure requiring medical therapy (diuretics, positive inotropes therapy, invasive and non-invavisve respiratory support) c) new onset of cardiac arrhythmias needing intervention d) unplanned ICU admission due to cardiac events. 3) Patients experience a significant raise in plasma catecholamines during surgery. Because of the association between intraoperative raise of catecholamines and postoperative cardiovascular risk we will also measure perioperative catecholamine (e.g. adrenaline, noradrenaline, dopamine) concentration. Supplemental oxygen leads to a decrease of sympathetic nerve activity followed by lower plasma catecholamine concentrations. Therefore, we perform a baseline measurement immediately after induction of anesthesia, one after surgery and one on third postoperative day. 4) The antioxidant capacity of a plasma sample, will be measured based on the electrical conductance relative to an internal reference standard. The plasma sample will be obtained preoperatively, hourly and immediately after end of surgery and on postoperative day 1 and 3 and before discharge but at least within 72hours. 5) Supplemental oxygen might have a vasopressor sparing effect. Consequently, the number of administered boluses as well as the total dose of phenylephrine and norepinephrine will be recorded. 6) The immune modulator effect of supplemental oxygen remains still unknown. Because of an enhanced endothelial vWF release during inflammation, we will further measure the vWF plasma level in order to evaluate the endothelial response to supplemental oxygen.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Troponin T will be measured within 2 hours after end of surgery, on postoperative day 1 and 3. 2) Outcome parameters concerning cardiac morbidity as mentioned before will be evaluated within 48 hours before hospital discharge and on postoperative day 30 through phone follow up. 3) Plasma catecholamines will be obtained within 2 hours after end of surgery and on postoperative day 1. 4) The oxidation-reduction of potential will be measured every hour during surgery, 2 hours within end of surgery and within 48 hours before hospital discharge. 5) The overall amount of administered vasopressor to maintain hemodynamic stability will be recorded. 6) Measurement of vWF will be performed within 2 hours after end of surgery, on postoperative day 1 and 3. |
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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 | No |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Comparison of intraoperative administration of different oxygen concentration (30% versus 80%) |
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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
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |