Chronic Kidney Diseases, Renal Transplantation
Conditions
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
Interventions
DRUGRemimazolam Besylate
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/
Sponsors
Qianfoshan Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Signed informed consent 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
Exclusion criteria
Hepatic, psychiatric, or neurological disorders 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 Major infection/trauma within 1 month prior Gastrointestinal surgery affecting drug absorption within 1 month prior Vaccination within 1 month prior or planned during study Blood loss/donation \>400 mL within 3 months prior Blood transfusion within 1 month prior INR \>1.5, PT \>ULN+4 seconds, or APTT \>15×ULN Significant bleeding history within 3 months prior Current anticoagulant therapy Any condition deemed unsuitable by investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sedation Depth (PD) | Induction: every 1minutes until MOAA/S≤1; Maintenance: every 10 minutes; Recovery: every 2 minutes until 3 consecutive MOAA/S=5. | MOAA/S score (0 to 5) + Narcotrend Index (NCI 0 to 100) |
| Narcotrend Index (NCI) Values | Continuous monitoring during infusion + 30 min post-stop | Anesthesia depth index (0-100 scale) |
| Time to Full Alertness (3 consecutive MOAA/S=5) | Time from infusion stop to sustained alertness | Time from infusion stop to sustained alertness |
| Time to Loss of Consciousness (MOAA/S ≤1) | 0 to 10 minutes after infusion start | Time from infusion start to first MOAA/S score ≤1 |
| CNS 7054 (Metabolite) PK Parameters | 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. | Maximum Plasma Concentration |
| Remimazolam 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. | Blood concentration (ng/mL) of Remimazolam |
| Remimazolam PK Parameters | 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. | Maximum Plasma Concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Agitation Incidence | PACU stay (0 to 2 hours) | RASS score ≥2 |
| Delayed Recovery Incidence | End of surgery to PACU discharge | Extubation time \>30 min post-surgery |
| Intraoperative Awareness Incidence | Upon PACU discharge (Day 1) | Positive Brice questionnaire response |
| Postoperative Nausea/Vomiting Incidence | PACU admission to Postoperation Day 6 | Postoperative Nausea/Vomiting occurrence |
| Intraoperative Bradycardia Incidence | Intra-operative period | HR \<45 bpm for \>1 min |
| Serum Creatinine Level | Preoperation, Postoperation Days 1 to 6 | Blood creatinine concentration |
| Estimated Glomerular Filtration Rate | Preoperation, Postoperation Days 1 to 6 | Kidney filtration rate |
| Intraoperative Hypotension Incidence | Intra-operative period | MAP \<65 mmHg for \>1 minute |
| Postoperative Urine Output | Postoperation Days 1 to 6 | 24-hour urine volume |
| Injection Pain Incidence | During induction (0 to 10 minutes) | Participant-reported pain during drug administration |
Other
| Measure | Time frame | Description |
|---|---|---|
| VDR Genotype Effect on Remimazolam Maximum Plasma Concentration | Pre-dose (Day 1) | Correlation of VDR polymorphisms with peak concentration |
| VDR Genotype Effect on CNS 7054 Terminal Elimination Half-Life | Pre-dose (Day 1) | Correlation of VDR polymorphisms with metabolite half-life |
| POR Genotype Effect on Remimazolam Clearance | Pre-dose (Day 1) | Correlation of POR polymorphisms with systemic clearance |
| CYP3A Genotype Effect on Remimazolam Area Under the Curve (0 to last measurable t) | Pre-dose (Day 1) | Correlation of CYP3A polymorphisms with total exposure |
Countries
China
Contacts
Primary Contactguanghan wu
Outcome results
None listed