Remimazolam Infusion in Kidney Transplant Patients: A Multicenter Study

NCT07045467 | Recruiting Phase 1

• 1 other identifier: YXLL-KY-2024(103)
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of remimazolam (CNS 70754) in healthy adult participants. The main questions it aims to answer are: What are the key pharmacokinetic parameters of remimazolam, including peak concentration (Cmax), time to peak concentration (Tmax), area under the curve (AUC), and elimination half-life (T1/2)? What is the effect of remimazolam on consciousness, as measured by the MOAA/S scale and Narcotrend monitoring during anesthesia? Researchers will compare the pharmacokinetic and pharmacodynamic effects of remimazolam to see if the drug provides consistent and predictable sedation without significant adverse effects. Participants will: Receive continuous Infusion of Remimazolam. Have blood samples taken at various time points to measure plasma concentrations and calculate PK parameters. Be monitored for consciousness and sedation levels using the MOAA/S scale and Narcotrend. Undergo safety assessments, including laboratory tests, vital signs monitoring, and physical examinations throughout the study. This study will help determine the drug's behavior in the body and its impact on sedation, providing valuable information for its future clinical use in anesthesia and other medical applications. Last updated on December 22, 2024

Conditions

Chronic Kidney Diseases; Renal Transplantation

Outcome Measures

Primary Outcomes (22)

• Remimazolam Plasma Concentration

  Blood concentration (ng/mL) of Remimazolam

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.

• Remimazolam PK Parameters

  Maximum Plasma Concentration

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.

• Remimazolam PK Parameters

  Area Under the Curve (0 to last measurable t)

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes

• Remimazolam PK Parameters

  Area Under the Curve (0 to infinity)

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes

• Remimazolam PK Parameters

  Time to Cmax

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes

• Remimazolam PK Parameters

  Terminal Elimination Half-Life

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes

• Remimazolam PK Parameters

  Total Body Clearance

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes

• Remimazolam PK Parameters

  Renal Clearance

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes

• Remimazolam PK Parameters

  Apparent Volume of Distribution (Terminal)

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes

• Remimazolam PK Parameters

  Mean Residence Time

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes

• Remimazolam PK Parameters

  Percentage of AUC Extrapolated

  Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes

• CNS 7054 (Metabolite) PK Parameters

  Maximum Plasma Concentration

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.

• CNS 7054 (Metabolite) PK Parameters

  Area Under the Curve (0 to last measurable t)

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.

• CNS 7054 (Metabolite) PK Parameters

  Area Under the Curve (0 to infinity)

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.

• CNS 7054 (Metabolite) PK Parameters

  Time to Cmax

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.

• CNS 7054 (Metabolite) PK Parameters

  Terminal Elimination Half-Life

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.

• CNS 7054 (Metabolite) PK Parameters

  Mean Residence Time

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.

• CNS 7054 (Metabolite) PK Parameters

  Percentage of AUC Extrapolated

  During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.

• Sedation Depth (PD)

  MOAA/S score (0 to 5) + Narcotrend Index (NCI 0 to 100)

  Induction: every 1minutes until MOAA/S≤1; Maintenance: every 10 minutes; Recovery: every 2 minutes until 3 consecutive MOAA/S=5.

• Time to Loss of Consciousness (MOAA/S ≤1)

  Time from infusion start to first MOAA/S score ≤1

  0 to 10 minutes after infusion start

• Time to Full Alertness (3 consecutive MOAA/S=5)

  Time from infusion stop to sustained alertness

  Time from infusion stop to sustained alertness

• Narcotrend Index (NCI) Values

  Anesthesia depth index (0-100 scale)

  Continuous monitoring during infusion + 30 min post-stop

Secondary Outcomes (10)

• Postoperative Urine Output

  Postoperation Days 1 to 6

• Serum Creatinine Level

  Preoperation, Postoperation Days 1 to 6

• Estimated Glomerular Filtration Rate

  Preoperation, Postoperation Days 1 to 6

• Intraoperative Hypotension Incidence

  Intra-operative period

• Intraoperative Bradycardia Incidence

  Intra-operative period

Other Outcomes (4)

• VDR Genotype Effect on Remimazolam Maximum Plasma Concentration

  Pre-dose (Day 1)

• CYP3A Genotype Effect on Remimazolam Area Under the Curve (0 to last measurable t)

  Pre-dose (Day 1)

• POR Genotype Effect on Remimazolam Clearance

  Pre-dose (Day 1)

Study Arms (1)

All enrolled participants receive Remimazolam Besylate via continuous IV infusion

EXPERIMENTAL

All enrolled participants receive a standardized Remimazolam Besylate-based anesthesia protocol for renal transplant surgery, as follows: 1. Intervention Drug: ◦ Remimazolam Besylate (Trade name: Rymazol®), supplied as a lyophilized powder (25 mg/vial) reconstituted with sterile water. 2. Dosing Regimen: * Induction: Continuous IV infusion at 6 mg/kg/h until loss of consciousness (defined as MOAA/S score ≤1). * Maintenance: Titrated IV infusion (0.5-2 mg/kg/h) to maintain target anesthesia depth (Narcotrend Index: 27-60) until end of surgery. 3. Ancillary Medications (per protocol §7.2): * Analgesia: Sufentanil (0.4-0.5 μg/kg induction; 10 μg at peritoneum closure) + Remifentanil infusion intraoperatively. * Muscle Relaxant: Rocuronium (0.6 mg/kg induction; 0.15 mg/kg bolus PRN). * Immunosuppression: Methylprednisolone 750 mg + Furosemide 60 mg pre-reperfusion. * Prohibited Agents: Sevoflurane, propofol, midazolam, dexmedetomidine, or etomidate. 4. Depth Monitoring: * Real-time Narcot

Drug: Remimazolam Besylate

Interventions

Remimazolam Besylate DRUG

This is the first clinical trial evaluating Remimazolam's pharmacokinetics (PK), pharmacodynamics (PD), and safety in renal transplant recipients-a population with unique physiological alterations due to end-stage renal disease and graft reperfusion. Key differentiators include: Population-Specific Dosing Protocol: Induction: 6 mg/kg/h until MOAA/S ≤1 (vs. 5-12 mg/kg/h in general surgery). Maintenance: Titrated (0.5-2 mg/kg/h) to Narcotrend Index 27-60 (lower than typical BIS 40-60 targets), accounting for altered drug metabolism post-transplant. Transplant-Specific Context: Administered alongside standard immunosuppressants (methylprednisolone 750 mg + furosemide 60 mg at reperfusion) but prohibits common sedatives (midazolam/propofol) to isolate Remimazolam's effects. PK/PD sampling accounts for graft function dynamics (e.g., blood draws during reperfusion and post-op days 1-6). Exploratory Genetic Analysis: First study linking VDR/

All enrolled participants receive Remimazolam Besylate via continuous IV infusion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years and \<65 years
• Chronic renal failure scheduled for renal transplantation
• Body mass index (BMI) 18-30 kg/m² (inclusive)
• Weight ≥50 kg (males) or ≥45 kg (females)
• ASA physical status classification III or IV

You may not qualify if:

• Coagulopathy
• Heart failure
• Respiratory failure
• Long-term sedative or antidepressant use
• Pregnancy or lactation
• Inability to communicate or cooperate
• Participation in other drug/device trials within 3 months prior
• Positive hepatitis B surface antigen (HBsAg)
• Positive hepatitis C antibody (HCV-Ab)
• Positive HIV antibody
• Positive syphilis antibody
• Use of hepatic enzyme inhibitors/inducers within 30 days prior (per Appendix 1)
• Known hypersensitivity to ≥2 substances
• Alcohol consumption \>14 units/week within 6 months prior\*
• Drug abuse history within 3 months prior

Sponsors & Collaborators

• Qianfoshan Hospital: lead

Study Sites (1)

Shandong First Medical University Hospital

Jinan, Shangdong, 250014, China

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

guanghan wu

CONTACT

+8618763995357; guanghanwu2021@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Anesthesiology and Perioperative Medicine

Study Record Dates

• First Submitted: June 5, 2025
• First Posted: July 1, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Locations

CN (1)