P-REMI trial

JRCT ID: jRCT2031230657

Registered date:27/02/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Japanese pediatric surgical patients undergoing general anesthesia
• Date of first enrollment: 19/02/2024
• Target sample size: 120
• Study type: Interventional

Intervention(s)

[Dose finding stage].
<Anesthesia induction phase>
CNS7056 is intravenously administered at a dose of 0.2 mg/kg per minute until the patients lose consciousness with the patient's general condition is observed. If the patients do not lose their consciousness even after the predetermined maximum dose is administered, another anesthetic is administered for anesthesia induction.
<Anesthesia maintenance phase>
After loss of consciousness due to CNS7056 administration, a continuous intravenous infusion of CNS7056 starts at the prescribed dose rate. The administration rate is adjusted to control anesthesia level while monitoring the general condition of the patients. If an attending anesthesiologist observes possible signs of arousal, a bolus dose of up to 0.2 mg/kg of CNS7065 is administered as needed. If signs of arousal continue, rescue alternative anesthetic is used for the following anesthesia maintenance and CNS7056 administration is terminated.
[Verification stage]
CNS7056 is administered for anesthesia induction and maintenance using the dose regimen determined on the results of the dose finding stage.

Outcome(s)

Primary Outcome

[Anesthesia induction] Percentage of patients who achieved loss of consciousness after the administration of CNS7056 alone
[Anesthesia maintenance]
Percentage of anesthetic efficacy that CNS7056 provides (1) no awareness and amnesia during general anesthesia, (2) no rescue administration of anesthetic during maintenance of anesthesia, and (3) intentional movement during anesthesia

Secondary Outcome

[Efficacy]
1. Time from start of CNS7056 administration to the patients' loss of consciousness
2. no anesthetic awareness and amnesia
3. no administration of rescue anesthetic during induction and maintenance of anesthesia
4. intentional movement during anesthesia
5. Patient State Index
6. Time from the end of CNS7056 administration to the following points
(1) extubation, (2) recovery of response to stimuli, (3) recovery to communicative status, and (4) to meet the criteria for discharge from the operating room

[Safety]
1. Adverse events
2. Side effect
3. Clinical laboratory tests results
4. Physical examination (blood pressure, heart rate, respiratory rate, body temperature, saturation of peripheral oxygen)
5.Electrocardiogram (12-lead ECG at rest, 3- or 5- lead ECG)
6. Percentage of patients with a >=30% reduction of systolic blood pressure compared to baseline
7. Number of vasopressor administration
8. Observation of CNS7056 administration site
9. Observation of emergence agitation
10. Presence or absence of flumazenil administration and re-sedation after the administration

[Pharmacokinetics]
Plasma concentrations of CNS7056 and CNS7054, which is a metabolite of CNS7056

Key inclusion & exclusion criteria

• Age minimum: >=
• Age maximum: < 18age old
• Gender: Both

Include criteria

1, A modified gestational age of>=45 weeks and <18 years old at the time of obtaining informed consent from a surrogate
2. Patients whose trachea are intubated, and who are artificially ventilated
3. Patients scheduled to be hospitalized for at least 3 days from the day before surgery to the day after surgery
4. American Society of Anesthesiologists physical status I-III
5. Patients who have been fully informed about the clinical trial, and a legal guardian (a surrogate) of the patients provide informed consent. Patients who provide informed assent, if the patient is a junior high school student or older. If the patient is under junior high school age, written assent is obtained whenever possible.

Exclude criteria

1. Pregnant, lactating girl, potential pregnant, or patients who cannot consent to contracept during the study period (from the time of obtaining consent to the end of all prescribed observations). For female patients of childbearing potential, a negative pregnancy urine test must be performed from the date of obtaining consent to prior to administration of the study drug
2. Patients scheduled to receive regional anesthesia (spinal anesthesia, epidural anesthesia, or peripheral nerve block) from the time of admission to the operating room until completion of tracheal intubation (excluding the use topical local anesthetic such as Emla cream to secure intravenous line for fluid infusion or blood sampling, and test dose of local anesthetic (<=3 mL) for epidural catheter placement
3. Patients scheduled to undergo neurosurgery (excluding spine and spinal cord surgery), hepatectomy, liver transplantation, or cardiac surgery (excluding catheter intervention)
4. Emergency surgery patient
5. Patients with a scheduled surgery time less than 1 hour
6. Patients with hypertension or hypotension requiring medical treatment
7. Obese (>=30% overweight) or emaciation (>20% underweight) classified using Weight-for-Height Charts
8. Patients who require respiratory management with tracheal intubation postoperatively, and patients expected to have delayed extubation
9. Patients who have received remimazolam within 1 month
10. Patients who are taking benzodiazepines regularly or have a history of tolerance to benzodiazepines
11. Patients with a history of hypersensitivity to benzodiazepines, remifentanil hydrochloride, fentanyl citrate, rocuronium bromide, sugammadex sodium, or flumazenil
12. Patients with a history of hypersensitivity to lactose and dextran
13. Patients with acute angle-closure glaucoma
14. Patients with myasthenia gravis or myasthenic syndrome
15. Patients in shock or coma
16. Patients with rate-responsive cardiac pacemakers
17. Patients whose electroencephalogram monitoring may be unavailable due to organic brain damage
18. Patients who are expected to excessive bleeding (e.g., >15% of circulating blood volume) during surgery
19. Patients with a history of severe allergy
20. Patients with drug dependence or with a history of drug dependence
21. Patients who receive another investigational drug within 120 days before the start of CNS7056 infusion
22. Patients who have been diagnosed with developmental delay or have communication difficulty excluding neonates, infants, toddlers, and preschoolers
23. Patients whom the investigator or subinvestigator determines to be inappropriate for inclusion in the clinical trial

Related Information

• Primary Sponsor: Masui Kenichi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,Mundipharma