Anaesthesia in adult patients undergoing cardiac surgery. MedDRA version: 16.0 Level: LLT Classification code 10021722 Term: Induction and maintenance anaesthesia System Organ Class: 100000004865
Conditions
Interventions
Product Name: Remimazolam for Injection 25mg
Product Code: CNS7056, ONO-2745
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Remimazolam
CAS Number: 1001415-66-2
Cur
Sponsors
PAION UK Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients scheduled for major elective cardiac surgery, i.e. 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 and surgery of the aortic arch • Scheduled to receive mechanical ventilation via tracheal intubation (oropharyngeal or nasotracheal) • Age at least 18 years • Weight between 55 and 150 kg inclusive • Body Mass Index (BMI) 18 to = 35 kg/m2 • Willingness and ability to give informed consent, to understand, participate and comply with all study requirements • For women with childbearing potential: negative pregnancy test Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: • Thoraco-abdominal replacement of the aorta or other procedure expected to be accompanied by a massive hemorrhage (at least 15% of the circulating blood volume) • History of or planned cooling below 34ºC • 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) • Severe renal insufficiency or end-stage renal disease (estimated glomerular filtration rate below 30 mL/min/1.73 m2) • Clinically uncontrolled coagulation abnormalities, or coagulation abnormalities not under adequate treatment • Total bilirubine =3.0 mg/dL or AST and/or ALT =2.5 x ULN during 7 days prior to starting administration of the investigational product • Scheduled for heart or lung transplantation • Infectious cardiac disorders (e.g. endocarditis, myocarditis) • Sepsis • Emergency surgery, status of shock or coma • Ejection fraction of less than 20% • Acute right heart failure • Pre-operative use of phosphodiesterase 3 inhibitors • History of resuscitation • Known resistance to benzodiazepines or history of paradoxical effects after administration of benzodiazepines • History of hypersensitivity to benzodiazepines, propofol, remifentanil hydrochloride, rocuronium bromide, flumazenil or other anesthetic agents • Use of benzodiazepines within 5 times their half-life or 5 times the half-life of their active metabolites. Exception: Single dose pre-medication before the surgery according to local standards is allowed. • Epilepsy • Myasthenia gravis or myasthenic syndrome • History of any severe allergy • Dependence from alcohol or drugs or history of alcohol or drug abuse • Acute alcoholic intoxication or ethanol intake within 48 hours prior to surgery • Acute narrow-angle glaucoma • Female patients of childbearing potential without acceptable method of birth control or not surgically sterile • Pregnant or breast feeding female patients • Patients in receipt of any investigational drug within 30 days or less than 7 half-lives (whichever was longer) before the start of the study , or scheduled to receive one during the study period • Administration of remimazolam in the past • Unable to communicate well with the investigator • Other reasons that, according to the investigator, exclude the patient from the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • to compare: - 2 doses of remimazolam against each other and against propofol during induction of general anesthesia and - remimazolam versus the combination of propofol and sevoflurane during maintenance of general anesthesia regarding efficacy and safety;Secondary Objective: • to collect data on pharmacokinetics to provide bridging to the PK data collected in Japanese subjects • to support the design of a phase III study in general anesthesia • to investigate pharmacoeconomic aspects For more details please see Secondary endpoints in Section E.5.2.;Primary end point(s): Efficacy: Proportion of patients with successful anesthesia, i.e. no use of rescue sedative.;Timepoint(s) of evaluation of this end point: Phase of general anaesthesia (Day 1). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: •Time to loss of consciousness •Time to intubation completed •Successful intubation •Time with Narcotrend index = 60 •Time to extubation •Time to discharge from PACU / ICU •Time on the IMC •Time to transfer to normal ward •Time to discharge from hospital •Intra-operative awakening/memory •Body motion •Use of rescue medication Safety: During general anesthesia and recovery: •Blood pressure, heart rate •Blood gas analysis •Bradycardia •Low cardiac output syndrome •Abnormalities in Narcotrend •Use of vasopressors •Duration of mechanical ventilation During general anesthesia only: •Ejection fraction •Cardiac output index •Cardiostability •Parameters measured via PICCO catheter •QTc prolongations During recovery from general anesthesia only: •Airway interventions •Adverse events post general anesthesia •Adverse events of special interest After recovery: •Post-operative admission to ICU when plan was to admit to PACU •Re-admission to ICU after discharge from ICU or PACU •Re-admission to the IMC •Re-surgery after 6 – 8 hours From screening through discharge •Increase of troponin, myocardial infarctions •Physical examination •Adverse events •General safety laboratory •Electrocardiogram •Cognitive function •Quality of life Pharmacokinetics, Pharmacoeconomics ;Timepoint(s) of evaluation of this end point: Phase of general anaesthesia (Day 1), phase of recovery (Day 1 to Day N) including phase of intensive care unit (ICU) sedation depending on the medical condition of the patient, follow up phase I (48 hours post discharge form post-anasthesia care unit or ICU), follow up phase II (starts at the end of FU phase I and ends with the discharge from the hospital). | — |
Countries
Germany
Contacts
Public ContactClinical trial information
PAION GmbH
Outcome results
None listed