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Clinical Phase III study in patients undergoing surgery to confirm ability of remimazolam to induce hypnotic effect in comparison with propofol

Phase 1
Conditions
Induction and maintenance of general anaesthesia (GA)
MedDRA version: 20.0Level: LLTClassification code 10018061Term: General anesthesiaSystem Organ Class: 100000004865
MedDRA version: 20.0Level: LLTClassification code 10054434Term: Induction and maintenance of anesthesiaSystem Organ Class: 100000004865
Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]
Registration Number
EUCTR2018-000174-29-FR
Lead Sponsor
PAION UK Limited
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
500
Inclusion Criteria

In order to be eligible to participate in this trial, an individual must meet all of the following 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 GA and planned to be extubated immediately post-operatively
• Total intravenous GA with the requirement for mechanical ventilation via endotracheal tube and necessary invasive BP monitoring either due to severity of illness, severity of concomitant diseases, type of surgery or decisions of the anaesthesia 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 urine pregnancy test taken shortly before the start of the administration of the IMP as well as consent to use highly effective birth control during the trial period (from the time of consent until the end of the trial follow-up procedures). 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.
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 350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this trial:
- Patients scheduled for spinal anaesthesia, epidural anaesthesia (central neuroaxial anaesthesia) or regional anaesthesia. The placement of a peridural catheter with a test dose application (up to 3 mL) to verify correct positioning to achieve post-operative analgesia and the regional administration of local anaesthetic for post-operative analgesia after wound closure is accepted.
- Patients undergoing transplant surgery, cardiac surgery, intracranial neurosurgery, 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 ICF and before arrival in the OR suite.
- Patients with total bilirubin of =3.0 mg/dL or =3 times increase in aspartate aminotransferase or alanine aminotransferase than the institutional reference range in laboratory tests during screening.
- Patients with end-stage renal disease 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 anaesthetic 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 on 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 difficult airways, known difficulties in airway maintenance or mask ventilation.
- Patients in whom NCT may not provide 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 prior to the beginning of administration of the IMP.
- 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 trial for any other reason

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: This is a confirmatory trial to establish non-inferior efficacy of remimazolam compared with propofol for induction and maintenance of GA for the purpose of elective surgery.;Secondary Objective: This is a confirmatory trial to establish superior haemodynamic stability associated with the use of remimazolam compared with propofol for the induction and maintenance of GA for the purpose of elective surgery.;Primary end point(s): The primary efficacy endpoint (PEP) is the anaesthetic effect of remimazolam and propofol assessed as percent (%) of time of Narcotrend (NCT) Index =60 during the maintenance phase of the GA defined as the time between the first skin incision and the completion of the last skin suture;Timepoint(s) of evaluation of this end point: During the maintenance phase of the GA
Secondary Outcome Measures
NameTimeMethod
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