Clinical phase II study of the sedative remimazolam in general narcosis in adult patients undergoing heart surgery, including subsequent care in the post-anaesthesia/intensive care unit, in order to evaluate the effects, tolerability, and metabolism of remimazolam

• Conditions: Anaesthesia in adult patients undergoing cardiac surgery.; MedDRA version: 16.0Level: LLTClassification code 10021722Term: Induction and maintenance anaesthesiaSystem Organ Class: 100000004865; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

• Registration Number: EUCTR2013-001113-32-DE
• Lead Sponsor: PAION UK Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-04-26
• Last Update Posted: 23 February 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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

• 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • to compare:<br>- 2 doses of remimazolam against each other and against propofol during induction of general anesthesia<br>and<br>- remimazolam versus the combination of propofol and sevoflurane during maintenance of general anesthesia<br>regarding efficacy and safety;Secondary Objective: • to collect data on pharmacokinetics to provide bridging to the PK data collected in Japanese subjects<br>• to support the design of a phase III study in general anesthesia<br>• to investigate pharmacoeconomic aspects<br><br>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).