Étude clinique pour confirmer l’efficacité et l’innocuité du remimazolam (CNS7056) comparé au propofol pour l’anesthésie intraveineuse en chirurgie non urgente

Drug: Remimazolam;Drug: Propofol

Inclusion criteria

- Male or female ASA III/IV patients at least 18 years old, scheduled for an elective
surgical procedure of a minimum duration of approximately 90 minutes under general
anesthesia (GA) and planned to be extubated immediately post-operatively.

- Total intravenous GA with the requirement for mechanical ventilation via endotracheal
tube and necessary invasive blood pressure (BP) monitoring either due to severity of
illness, severity of concomitant diseases, type of surgery or decisions of the
anesthesia staff.

- Patients scheduled to stay in the hospital long enough after the surgical procedure to
perform all trial follow-up procedures (~1 day)

- For female patients of childbearing potential: Negative result of a pregnancy test
taken shortly before the start of the administration of the IMP as well as consent to
use highly effective birth control from the last menstrual cycle prior to the start of
the IMP until the end of the trial follow-up procedures. Highly effective methods of
birth control include:

- Combined (estrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation: oral, intravaginal and transdermal

- Progestogen-only hormonal contraception associated with inhibition of ovulation:
oral, injectable and implantable

- Intrauterine device (IUD)

- Intrauterine hormone-releasing system (IUS)

- Bilateral tubal occlusion

- Vasectomised partner (provided that the partner is the sole sexual partner of the
female patient of childbearing potential and that the vasectomised partner has
received medical assessment of the surgical success)

- Sexual abstinence (this method is not acceptable in Switzerland)

Women who had their last menstruation at least two years ago or who underwent surgical
interventions (surgical birth control, bilateral oophorectomy, hysterectomy, etc.) are
regarded as having no childbearing potential

Exclusion criteria

- Patients scheduled for spinal anesthesia, epidural anesthesia (central neuraxial
anesthesia) or regional anesthesia. The placement of a peridural catheter with a test
dose application of a local anesthetic drug (up to 5 mL) to verify correct positioning
to achieve post-operative analgesia and the regional administration of local
anesthetic for post-operative analgesia after wound closure is accepted.

- Patients undergoing transplant surgery, cardiac surgery, or intracranial neurosurgery,
patients which have to be in prone position for surgery, emergency surgery, or any
surgical procedure with the need for or scheduled for post-operative ventilator
support.

- Patients undergoing surgical procedures that require keeping the BP at a high level,
e.g. surgical procedures in beach chair position

- Patients with severe hypertension, i.e., one baseline result of systolic BP 200 mmHg
or more and / or diastolic BP of 120 mmHg or more. Baseline is defined as the time
after signature of the informed consent form (ICF) and before arrival in the operating
room (OR) suite.

- Patients with total bilirubin of =3.0 mg/dL or =3 times increase in aspartate
aminotransferase (ASAT) or alanine aminotransferase (ALAT) than the institutional
reference range in laboratory tests, or any other laboratory results that make the
patient unsuitable for the trial. All laboratory tests relevant for subject's
enrolment must be performed within 7 days prior to start of IMP*

* If the screening samples for the central laboratory were taken earlier than within
the last 7 days prior to start of IMP, the lab parameters relevant for subject's
enrolment are to be determined in a local laboratory within 7 days prior to start of
IMP. If results from samples taken within 7 days prior to the start of the IMP/the
surgery from a local laboratory are available, these can be used. If no results from
the last 7 days prior to the start of the IMP/the surgery are available, samples need
to be taken for the purpose of this trial and to be analysed in a local laboratory.

- Patients with end stage renal disease (ESRD) requiring scheduled dialysis

- Patients with known anaphylactic reactions to benzodiazepines, propofol, opioid
analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), dextran, neuromuscular
blocking agents, flumazenil, naloxone, or other anesthetic agents, or a medical
condition such that these agents are contraindicated (according to local label)

- Presence of acute alcoholic or illicit drug intoxication, shock or coma state

- Known current dependency from central nervous system depressant drugs or alcohol

- Patients with gastroparesis or delayed gastric emptying, gastric reflux or any other
increased risk for gastric aspiration

- Patients with an anticipated (small mouth opening, impaired neck movement, goitre,
head and neck tumours or any other anatomical reason) or known airway difficulties or
with known difficulties in airway maintenance or mask ventilation

- Patients in whom Narcotrend (NCT) may not provide reliable results due to organic
defect of the brain or forehead, or any neurologic disease interfering with the EEG
monitoring

- Patients on treatment with valproate

- Any pregnant or breast-feeding patient

- Patients who participated in any clinical trial within 30 days or 5 times the
half-life of the drug under investigation, whichever is longer, prior to the beginning
of administration of the IMP. Exception: Non-interventional trials as defined in the
European Clinical Trials Directive 2001/20/EC: A trial where the medicinal product(s)
is (are) prescribed in the usual manner in accordance with the terms of the marketing
authorisation. The assignment of the patient to a particular therapeutic strategy is
not decided in advance by a trial protocol but falls within current practice and the
prescription of the medicine is clearly separated from the decision to include the
patient in the study. No additional diagnostic or monitoring procedures shall be
applied to the patients and epidemiological methods should be used for the analysis of
the collected data.

- Any patient judged to lack the ability to give informed consent or perform the trial
assessments (e.g., due to dementia)

- Any patient judged by the Principal Investigator (PI) or Sub-Investigator to be
inappropriate for the subject for any other reason