A Randomized, Single-blind, Propofol-controlled Phase III Study Evaluating the Efficacy and Safety of Remimazolam in GA in Adult Patients Undergoing Cardiac Surgery, Including Follow-up Sedation in the Post-anesthesia Care Unit/ICU
Overview
- Phase
- Phase 3
- Intervention
- Propofol
- Conditions
- Anesthesia
- Sponsor
- Paion UK Ltd.
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Success of Procedure
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This study investigates the use of remimazolam as a sedative/hypnotic in general anesthesia. Remimazolam or propofol will be administered together with fentanyl/sufentanil/remifentanil as opioid analgesics and a neuromuscular blocker.
In total, 530 patients will be randomized. This group of 530 patients will be split randomly into 2 groups as follows:
• 106 patients will be randomized to induction with propofol plus fentanyl or sufentanil or remifentanil and a neuromuscular blocker. Throughout maintenance, the patients will receive propofol and remifentanil until weaning from the mechanical ventilation on the ICU or PACU within 24 hours after induction.
Afterwards, sedation with propofol as study medication has to be ended. If necessary, the sedation is to be continued with the hospital's own supplies (propofol or other sedative).
• 424 patients will be randomized to induction with remimazolam 6.0 mg/kg/hr together with fentanyl or sufentanil or remifentanil and a neuromuscular blocker. Throughout maintenance, the patients will receive remimazolam and remifentanil until weaning from the mechanical ventilation on the ICU or PACU within 24 hours after induction.
The primary endpoint is 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Scheduled for major non-emergency 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(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 18 to ≤40 kg/m2
- •Willingness and ability to give informed consent, to understand, participate and comply with all study requirements
- •For women of childbearing potential: negative pregnancy test (serum or urine strip) as well as using a highly effective method of birth control. Such methods include:
- •Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, with the following routes of administration: oral, intravaginal, transdermal
- •Progestogen-only hormonal contraception associated with inhibition of ovulation, with the following routes of administration: oral, injectable, implantable
- •Intrauterine device
- •Intrauterine hormone-releasing system
Exclusion Criteria
- •Re-do cardiac surgery
- •Surgical procedures that comprised the use of drugs and/or devices that were not approved for marketing
- •Severe tricuspidal insufficiency (III grade)
- •Planned cooling of the patient's body 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, excluded patients from the study
- •Poorly controlled hypertension (e.g. systolic blood pressure ≥160 mmHg under antihypertensive medication at screening)
- •Patients with 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). Measuring only one of both parameters was sufficient to assess the eligibility of a patient.
- •Patients with clinically uncontrolled coagulation abnormalities, or with coagulation abnormalities not under adequate treatment
Arms & Interventions
Propofol
Propofol for induction will be given as a bolus administered manually at 2.0-2.5 mg/kg slowly over approximately 1 minute. Immediately after the propofol bolus for induction has been given, propofol maintenance will be started at a dose of 3.0-9.0 mg/kg/hr and adjusted as needed.
Intervention: Propofol
Remimazolam
Remimazolam for induction will be given at 6.0 mg/kg/hr, which can be increased to 12.0 mg/kg/hr for one minute if loss of consciousness is not reached after 3 minutes. Immediately after the remimazolam dose for induction has been given, remimazolam maintenance will be given at 1.0 mg/kg/hr and adjusted by down-titration or up-titration to a maximum of 3.0 mg/kg/hr.
Intervention: Remimazolam
Outcomes
Primary Outcomes
Success of Procedure
Time Frame: During maintenance phase of operation - between arrival at operation theatre and completion of last skin suture (estimated up to 24 hours).
A narcotrend index of 60 or less during at least 85% of the maintenance time and no rescue sedative medication administered.
Secondary Outcomes
- Hemodynamic stability(From the start of study medication until completion of the last skin suture (estimated up to 24 hours).)