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EUCTR2018-000174-29

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

Datenbasis: WHO (Import vom 26.01.2020)
Geändert: 22.12.2019
Krankheitskategorie:

Health conditions (Datenquelle: WHO)

Induction and maintenance of general anaesthesia (GA)
MedDRA version: 21.1Level: LLTClassification code 10018061Term: General anesthesiaSystem Organ Class: 100000004865
MedDRA version: 21.1Level: 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]

Interventions (Datenquelle: WHO)


Product Name: Remimazolam
Product Code: CNS7056
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Remimazolam
Current Sponsor code: CNS7056
Other descriptive name: REMIMAZOLAM
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Trade Name: Propofol
Product Name: Propofol
Pharmaceutical Form: Emulsion for injection/infusion
INN or Proposed INN: PROPOFOL
Other descriptive name: PROPOFOL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Inclusion/Exclusion Criteria (Datenquelle: WHO)

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 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 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 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 postoperative 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 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), dextran, 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 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 s

Weitere Angaben zur Studie im WHO-Primärregister

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000174-29

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2018-000174-29-NL

Weitere Informationen zur Studie

Registrationsdatum der Studie

23.05.2018

Einschluss der ersten teilnehmenden Person

09.10.2018

Rekrutierungsstatus

Authorised-recruitment may be ongoing or finished

Wissenschaftlicher Titel (Datenquelle: WHO)

Phase III confirmatory efficacy and safety trial of remimazolam (CNS7056) compared with propofol for intravenous anaesthesia during elective surgery

Studientyp (Datenquelle: WHO)

Interventional clinical trial of medicinal product

Design der Studie (Datenquelle: WHO)

Controlled: yesRandomised: yesOpen: noSingle blind: yesDouble blind: noParallel group: yesCross over: noOther: noIf controlled, specify comparator, Other Medicinial Product: yesPlacebo: noOther: noNumber of treatment arms in the trial: 2

Phase (Datenquelle: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no

Primäre Endpunkte (Datenquelle: WHO)

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

Sekundäre Endpunkte (Datenquelle: WHO)

Timepoint(s) of evaluation of this end point: During the maintenance phase of the GA;Secondary end point(s): The key secondary endpoint (KSE) is haemodynamic instability defined as critical decrease(s) in mean arterial blood pressure (MAP) between start of IMP and 15 minutes after the first skin incision.
For this endpoint, each event from the following categories will be counted and summed up per patient:
• Incidence of MAP dropping below 65 mmHg for at least 1 minute duration
• Incidence of a MAP decrease of more than 20% below the calculated (mean) baseline MAP value for at least 1 minute duration
• Incidence of a MAP decrease of more than 30% below the calculated (mean) baseline MAP value for at least 1 minute duration
• Number of norepinephrine boluses (0.01 mg) required or, if an infusion is used to maintain MAP equal to or above 65 mmHg, then each time interval of 2 minutes duration of continuous norepinephrine infusion will be counted as one event.
The baseline MAP is calculated based on all blood pressure (BP) measurements that are taken after signing the informed consent form (ICF) and before arrival at the operation room (OR) suite.
This endpoint is a safety endpoint.
Other secondary endpoints for efficacy comprise
• Percentage of time of NCT index (NCI) =60 and =40 during the maintenance phase
• Percentage of time of NCI <40 during the maintenance phase
• Percentage of patients with NCI =60 and =40 during =90% of the maintenance phase
• Percentage of patients who were administered rescue sedative medication
• The occurrence of intra-operative awakening (explicit awareness)
• Time from start of IMP to first NCI =60
• Time from start of IMP to loss of palpebral reflex
• Time from start of IMP to loss of consciousness (LOC, i.e., modified observer’s assessment of alertness / sedation [MOAA/S] = 0)
• Time from stop of IMP to response to verbal command (MOAA/S =4)
• Time from stop of IMP to end of extubation
• Time from stop of IMP to orientation to time, place, person and situation
• Time from stop of IMP to Modified Aldrete Score = 10
• Investigator’s overall satisfaction with IMP

Kontakt für Auskünfte (Datenquelle: WHO)

PAION UK Limited

Studiendurchführungsorte

Durchführungsländer (Datenquelle: WHO)

Belgium, Denmark, France, Germany, Italy, Netherlands, Switzerland, United Kingdom

Kontakt für weitere Auskünfte zur Studie

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

Clinical Trial Information
Martinstrasse 10-12
PAION Deutschland GmbH
00492414453101
info@paion.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Clinical Trial Information
Martinstrasse 10-12
PAION Deutschland GmbH
00492414453101
info@paion.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

PAION UK Limited

Weitere Studienidentifikationsnummern

Secondary ID (Datenquelle: WHO)

CNS7056-022;2018-000174-29-DE