Population Pharmacokinetics and Pharmacodynamics of Ciprofol

NCT ID: NCT07301242

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-10-28

Study Completion Date

2026-12-31

Brief Summary

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The goal of this observational study is to learn how the anesthetic drug ciprofol works in older adults who are having limb surgery under general anesthesia at Shanghai Geriatric Medical Center. The study will help researchers build a population model to better understand how the drug moves through the body (PK) and how it affects patients (PD). This model may help doctors use a Target-Controlled Infusion (TCI) system to adjust the drug dose more precisely.

The main question it aims to answer is: Does ciprofol work safely and effectively in older adults during orthopedic surgery?

Participants already receiving ciprofol as part of their regular anesthesia care will:

1. Provide blood samples at different time points during and after surgery.
2. Have their vital signs and anesthesia-related data recorded before, during, and after surgery.
3. Be monitored for side effects and recovery indicators such as the Aldrete score and signs of postoperative delirium.

Researchers will use this information to:

1. Build and test a population PK/PD model for ciprofol.
2. Simulate recommended TCI dosing plans.
3. Explore how individual responses to ciprofol relate to recovery and safety outcomes.

This study may help improve anesthesia care for elder adults by making drug dosing safer and more effective.

Detailed Description

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Elderly patients undergoing orthopedic limb surgery represent a growing population with unique perioperative challenges. Age-related physiological changes-including reduced hepatic and renal function, altered body composition, and decreased cardiac output-significantly affect the pharmacokinetics (PK) and pharmacodynamics (PD) of anesthetic drugs. These changes increase the difficulty of maintaining adequate anesthesia depth and hemodynamic stability.

Ciprofol, a novel intravenous anesthetic, has shown promising efficacy and safety in clinical practice. However, existing PK/PD models are largely derived from healthy volunteers or younger patients, and cannot adequately predict drug behavior in elderly orthopedic patients who often present with comorbidities and heightened surgical stress. This gap may lead to risks such as drug accumulation and circulatory depression, or insufficient dosing and intraoperative awareness.

This single-center, observational, prospective study at Shanghai Geriatric Medical Center aims to construct and validate a population PK/PD model of ciprofol specifically for elderly patients undergoing orthopedic limb surgery. The model will support precise control of effect-site concentration via Target-Controlled Infusion (TCI) systems, enabling individualized anesthesia management.

Study Objectives 1.Primary Objective: To develop and validate a population PK/PD model of ciprofol tailored to elderly orthopedic patients, and to evaluate its accuracy in predicting effect-site concentrations.

2.Secondary Objectives:

1. To simulate recommended TCI dosing regimens based on the new model and compare them with current drug label recommendations, assessing clinical value and optimization potential.
2. To evaluate the anesthetic efficacy and safety of ciprofol in this patient population.

3.Exploratory Objectives: To investigate the influence of covariates (e.g., age, sex, BMI, hepatic and renal function) on PK/PD parameters, and to explore correlations between individual PK/PD parameters and recovery outcomes such as Aldrete score and postoperative delirium incidence.

Study Design

1.Type: Single-center, observational, biosample-utilization study. 2.Population: 45 elderly patients (≥65 years, ASA I-III) scheduled for elective orthopedic limb surgery under general anesthesia.

3.Procedures:

1. Collection of perioperative clinical data (vital signs, BIS monitoring, anesthesia-related indicators).
2. Serial blood sampling at predefined time points for plasma concentration measurement.
3. Monitoring of anesthetic efficacy (induction success, BIS values, recovery times) and safety endpoints (hypotension, bradycardia, hypoxemia, injection pain).

4.Endpoints:

1. Primary Endpoint: Accuracy of the population PK/PD model in predicting effect-site concentrations.
2. Secondary Endpoints: Differences between model-recommended dosing and label-based dosing; incidence of ciprofol-related adverse events; anesthetic efficacy indicators.
3. Exploratory Endpoints: Covariate effects on PK/PD parameters; correlation of PK/PD parameters with Aldrete score recovery and postoperative delirium.

Data Management and Analysis All perioperative data will be recorded and stored electronically, with double-entry verification and query resolution procedures to ensure accuracy. PK/PD modeling will be performed using nonlinear mixed-effects modeling (NONMEM). Model evaluation will include goodness-of-fit plots, visual predictive checks, and bootstrap validation. Simulations will be conducted to compare TCI dosing regimens derived from the new model with standard recommendations.

Expected Significance This study will fill an important gap in anesthetic pharmacology by providing a validated PK/PD model of ciprofol for elderly orthopedic patients. The findings are expected to improve perioperative anesthesia management, enhance patient safety, and support individualized dosing strategies in clinical practice.

Conditions

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Hip Fractures (ICD-10 72.01-72.2) Osteoarthritis, Knee and Hip Femoral Neck Fractures

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Elderly Orthopedic Limb Surgery Cohort

Inclusion Criteria:

Age ≥65 years; BMI 18-30 kg/m²; ASA physical status classification I-III; Scheduled for elective orthopedic limb surgery under general anesthesia; Expected duration of surgery \>30 minutes; Willing to participate and able to provide written informed consent.

Exclusion Criteria:

Known allergy to ciprofol or related medications, or any contraindication to their use; Preoperative cognitive impairment (Mini-Cog score \<3); History of severe cerebrovascular disease or related complications; History of neuromuscular system diseases or psychiatric disorders; History of sedative medication use; History of alcohol abuse or substance use disorder; Bradycardia (heart rate \<60 beats per minute); Hypotension (mean arterial pressure \<55 mmHg); QT interval prolongation; Uncooperative or unable to communicate effectively.

Ciprofol

Intervention Type DRUG

Ciprofol is used as an intravenous anesthetic agent for sedation and anesthesia induction/maintenance in elderly patients undergoing elective orthopedic limb surgery. In this observational study, ciprofol is administered according to standard clinical practices, and data on its pharmacokinetics, pharmacodynamics, safety, and effectiveness in this specific population will be collected.

Interventions

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Ciprofol

Ciprofol is used as an intravenous anesthetic agent for sedation and anesthesia induction/maintenance in elderly patients undergoing elective orthopedic limb surgery. In this observational study, ciprofol is administered according to standard clinical practices, and data on its pharmacokinetics, pharmacodynamics, safety, and effectiveness in this specific population will be collected.

Intervention Type DRUG

Other Intervention Names

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Cipepofol Sishuning

Eligibility Criteria

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Inclusion Criteria

* Age ≥65 years;
* BMI: 18-30 kg/m²;
* ASA physical status classification I-III;
* Scheduled for elective orthopedic limb surgery under general anesthesia;
* Expected duration of surgery \>30 minutes;
* Willing to participate and able to provide written informed consent.

Exclusion Criteria

* Known allergy to ciprofol or related medications, or any contraindication to their use;
* Preoperative cognitive impairment;
* History of severe cerebrovascular disease or related complications;
* History of neuromuscular system diseases or psychiatric disorders;
* History of sedative medication use;
* History of alcohol abuse or substance use disorder;
* Bradycardia (heart rate \<60 beats per minute);
* Hypotension (mean arterial pressure \<55 mmHg);
* QT interval prolongation;
* Uncooperative or unable to communicate effectively.
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shanghai Geriatric Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Xue Zhang

Attending Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Xue Zhang

Role: PRINCIPAL_INVESTIGATOR

Shanghai Geriatric Medical Center

Locations

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Shanghai Geriatric Medical Center

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Xue Zhang

Role: CONTACT

Phone: 02164175590

Email: [email protected]

Facility Contacts

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Clinical Research Coordinator

Role: primary

Other Identifiers

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ZCLY2025-021

Identifier Type: -

Identifier Source: org_study_id