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-GB

Lead Sponsor: PAION UK Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 512

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 results of 2 pregnancy tests, the first test taken at the start of Screening and the second test taken shortly before the start of the administration of the IMP as well as consent to use highly effective birth control from the 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:
o Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- Oral / intravaginal / transdermal
o Progestogen-only hormonal contraception associated with inhibition of ovulation:
- Oral / injectable / implantable
o Intrauterine device (IUD)
o Intrauterine hormone–releasing system (IUS)
o Bilateral tubal occlusion
o 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).
o Sexual abstinence
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 358
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 154

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 local anaesthetic drug (up to 5 mL) to verify correct positioning to achieve post-operative analgesia and the regional administration of local anaesthetic for post-operative analgesia after wound closure (after the last skin suture) 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 as per reference range in laboratory tests which must be checked within the 7 days prior to start of IMP, or any other laboratory results that make the patient unsuitable for the trial.
- 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), neuromuscular blocking agents, flumazenil, naloxone, or other anaesthetic agents, or a medical condition such that these agents are contraindicated (according to local label). Patients with allergy/hypersensitivity to bovine lactose, dextran or any other excipient in the remimazolam product.
- Presence of acute alcoholic or illicit drug intoxication, shock or coma state
- Known current dependency on or regular use of 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 airways difficulties, 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 or 5 times the half-life of the drug under investigation in any other clinical trial, 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method

Related Trials