E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anesthesia in adult patients undergoing cardiac surgery. |
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E.1.1.1 | Medical condition in easily understood language |
Sedation in adult patients undergoing cardiac surgery. |
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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 | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021722 |
E.1.2 | Term | Induction and maintenance anaesthesia |
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 |
To show non-inferiority of remimazolam compared with propofol in terms of successful maintenance of sedation during general anesthesia defined as Narcotrend index of 60 or less during at least 85% of the maintenance time without the use of rescue sedative medication. |
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E.2.2 | Secondary objectives of the trial |
•to show superiority of remimazolam compared with propofol in terms of haemodynamic stability •to assess the efficacy of remimazolam compared with propofol •to assess the safety of remimazolam compared with propofol •to assess quality of life •to investigate pharmacokinetics in patients exposed for more than 24 hours • to collect data potentially relevant for pharmacoeconomics |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Patients scheduled for major non-emergency cardiac surgery assumed to require more than 2 hours of maintenance of general anesthesia and to require the use of extracorporeal circulation, including coronary bypass(es), valve replacement(s) and associated procedures and on-pump minimal invasive surgery •Scheduled to receive mechanical ventilation via tracheal intubation (oropharyngeal or nasotracheal) •Age at least 18 years •Body Mass Index (BMI) 18 to ≤ 40 kg/m2
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E.4 | Principal exclusion criteria |
•Re-do cardiac surgery •Surgical procedures that comprise the use of drugs and/or devices that are not approved for marketing •Severe tricuspidal insufficiency •Planned cooling below 32ºC •History of or planned stop of circulation, e.g. due to repair of type A dissection of aorta or removal of thrombi from pulmonary artery •Planned to receive epidural/spinal anesthesia together with general anesthesia •Evidence of uncontrolled hepatic, central nervous system, respiratory, or metabolic dysfunction, or other clinically significant findings at screening that, in the investigator’s or medical monitor’s opinion, should exclude them from the study. •Poorly controlled hypertension (e.g. systolic blood pressure ≥160 mmHg under antihypertensive medication at screening) •Severe renal insufficiency or end-stage renal disease (creatinine clearance below 30 mL/min or estimated glomerular filtration rate below 30 mL/min/1.73 m2). •Clinically uncontrolled coagulation abnormalities, or coagulation abnormalities not under adequate treatment •Scheduled for heart or lung transplantation •Infectious cardiac disorders (e.g. endocarditis, myocarditis) •Sepsis •Emergency surgery, status of shock or coma •Ejection fraction from left ventricle of less than 20% •Acute right heart failure
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E.5 End points |
E.5.1 | Primary end point(s) |
Successful sedation is defined as a Narcotrend index of 60 or less during at least 85% of the maintenance time and no rescue sedative medication administered. The maintenance starts at arrival at the operation theater and ends with the completion of the last skin suture. In clinics with no change in the location of the patient between induction and start of the surgery, maintenance starts when the anesthesiologist permits the surgical team to start the surgical procedure including preparation of the surgical site(s). The primary endpoint is an efficacy endpoint.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase of general anesthesia (Day 1). |
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E.5.2 | Secondary end point(s) |
The haemodynamic stability is expressed in terms of the amount of norepinephrine actually administered per body weight and time between start of the study medication (remimazolam or propofol) for induction of the general anesthesia and the completion of the last skin suture. A lower amount of norepinephrine actually administered corresponds to a higher hemodynamic stability. The key secondary endpoint is a safety endpoint.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Phase of general anesthesia (Day 1). |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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) | 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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Germany |
Netherlands |
Poland |
Switzerland |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |