Fospropofol Disodium ED95 for Elderly Spinal Anesthesia Sedation

95% Effective Dose (ED95) of Fospropofol Disodium for Adjunctive Sedation During Spinal Anesthesia in Elderly Patients Undergoing Lower Extremity Surgery

This study aims to determine the 95% effective dose (ED95) of fospropofol disodium, a new sedative drug, for adjuvant sedation during spinal anesthesia in elderly patients (aged 65 years and older) undergoing lower extremity surgery (e.g., hip/knee replacement, lower limb fracture fixation).

Study Overview

• Status: Not yet recruiting
• Conditions: Lower Extremity Surgery
• Intervention / Treatment: Drug: Fospropofol Disodium

Detailed Description

Fospropofol disodium, the only water-soluble propofol prodrug marketed in China, features mild effects on respiratory and circulatory systems, low injection pain, no lipid metabolism-related adverse reactions, and suitable duration of action-making it a promising sedative for elderly patients. However, clinical data on its use in adjuvant sedation during spinal anesthesia are lacking, with no reports on its effective dose in this specific scenario. This prospective sequential trial aims to determine the 95% effective dose (ED95) of fospropofol disodium for sedation induction and maintenance in elderly patients (≥65 years) undergoing lower extremity surgery with spinal anesthesia, providing evidence-based guidance for safe and rational clinical use.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ya-Qun Zhou, Dr.; Phone Number: +86-027-83663171; Email: yqzhou2019@hust.edu.cn
• Study Contact Backup: Name: Xi-Jian Ke, Dr.; Phone Number: +86-027-83665431; Email: kexijian@hust.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥65 years, no gender restriction
• Scheduled for elective lower extremity surgery with spinal anesthesia
• ASA physical status classification Ⅰ-Ⅲ
• BMI 18.5-28.0
• Written informed consent obtained from patients or their guardians

Exclusion Criteria:

• Age <65 years；
• Non-lower extremity surgery or conversion to general anesthesia；
• ASA physical status classification Ⅳ or above；
• BMI <18.5 or >28.0；
• History of drug abuse or alcohol dependence；
• Preoperative use of sedative or analgesic drugs；
• Refusal to participate or inability to sign informed consent；
• Severe arrhythmia or myocardial infarction within 3 months；
• Severe liver or kidney dysfunction；
• Severe respiratory diseases；
• Coagulopathy；
• Uncorrected severe electrolyte disturbance；
• History of mental illness or cognitive impairment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fospropofol Disodium - Sedation ED95 Exploration; This arm aims to explore the 95% effective dose (ED95) of fospropofol disodium for sedation in elderly patients undergoing lower extremity surgery with spinal anesthesia.

Drug: Fospropofol Disodium; The initial induction dose is 6.0mg/kg, with a dose gradient of 0.5mg/kg (range: 4.0-8.0mg/kg). Sedation success is defined as a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score ≤3 within 3 minutes after drug administration. Dose adjustment follows the k=3 sequential design: ① 3 consecutive successes → next patient receives a 0.5mg/kg lower dose; ② 1 failure → next patient receives a 0.5mg/kg higher dose; ③ 2 consecutive failures → skip the next gradient. Immediately after successful induction (MOAA/S ≤3 within 3 minutes), continuous infusion of fospropofol disodium for sedation maintenance will be initiated. The initial maintenance rate is 6.0mg/kg/h, with a gradient of 0.5mg/kg/h (range: 3.0-7.5mg/kg/h). Maintenance success is defined as MOAA/S score ≤3 in ≥4 of 6 assessments (once every 10 minutes). Dose adjustment follows the k=3 sequential design: ① 3 consecutive successes → next patient receives a 0.5mg/kg/h lower rate; ② 1 failure → next patient receives a 0.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
95% Effective Dose (ED95) of Fospropofol Disodium for Sedation in Elderly Patients Undergoing Lower Extremity Surgery with Spinal Anesthesia	The primary outcome is the 95% effective dose (ED95) of fospropofol disodium for adjuvant sedation during spinal anesthesia in elderly patients (≥65 years), including two key components: ① Induction ED95: The intravenous bolus dose at which 95% of patients achieve a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score ≤3 within 3 minutes of administration (dose range: 4.0-8.0mg/kg, gradient: 0.5mg/kg); ② Maintenance ED95: The continuous intravenous infusion rate at which 95% of patients maintain an MOAA/S score ≤3 in ≥4 out of 6 intraoperative assessments (performed every 10 minutes) after successful induction (rate range: 3.0-7.5mg/kg/h, gradient: 0.5mg/kg/h). Both ED95 values (and their 95% confidence intervals [CI]) will be calculated using Probit regression analysis, with sedation success (effective=1, ineffective=0) as the dependent variable and dose/rate as the independent variable.	① Induction ED95: Assessed at 3 minutes after completion of the fospropofol disodium induction bolus; ② Maintenance ED95: Assessed throughout the intraoperative maintenance phase (6 evaluations, 10 minutes apart).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Induction Onset Time of Fospropofol Disodium	The time from the start of fospropofol disodium bolus injection (sedation induction phase) to the first achievement of a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score ≤3.	From the start of fospropofol disodium bolus injection to the first achievement of MOAA/S score ≤3, assessed up to 5 minutes.
Recovery Time After Sedation Maintenance Discontinuation	The time from the cessation of fospropofol disodium continuous infusion (start of surgical skin closure) to the recovery of MOAA/S score to 5 (full alertness, rapid response to name called in normal tone).	From the moment of maintenance infusion cessation (start of surgical skin closure) to the time when MOAA/S score returns to 5, assessed up to 30 minutes.
Incidence of Respiratory Depression	The proportion of patients with respiratory depression, defined as either respiratory rate <8 breaths per minute (bpm) or oxygen saturation (SpO₂) <90% (sustained for ≥10 seconds) during the entire sedation period (induction + maintenance).	Throughout the sedation period (from induction drug injection to maintenance infusion cessation) and within 10 minutes postoperatively.
Intraoperative Changes in Mean Arterial Pressure (MAP)	Change in mean arterial pressure (MAP) relative to baseline value (recorded after lumbar anesthesia stabilization pre-sedation). Key observation points include: 1 minute, 3 minutes, 5 minutes post-induction; and at each MOAA/S assessment time point during maintenance (every 10 minutes). The maximum decrease/increase percentage of MAP from baseline is calculated (e.g., maximum MAP decrease = [(baseline MAP - intraoperative minimum MAP)/baseline MAP] × 100%).	Baseline (pre-sedation), 1/3/5 min post-induction, and every 10 minutes during maintenance.
Intraoperative Changes in Heart Rate (HR)	Change in heart rate (HR) relative to baseline value (recorded after lumbar anesthesia stabilization pre-sedation). Key observation points include: 1 minute, 3 minutes, 5 minutes post-induction; and at each MOAA/S assessment time point during maintenance (every 10 minutes). The maximum decrease/increase percentage of HR from baseline is calculated (e.g., maximum HR decrease = [(baseline HR - intraoperative minimum HR)/baseline HR] × 100%).	Baseline (pre-sedation), 1/3/5 min post-induction, and every 10 minutes during maintenance.
Incidence of Postoperative Adverse Reactions	The proportion of patients experiencing adverse reactions within 24 hours postoperatively, including: Cardiovascular reactions: Hypertension (SBP >160 mmHg or increase of ≥30% from baseline), tachycardia (HR >100 bpm); Gastrointestinal reactions: Nausea, vomiting; Neurological/psychological reactions: Postoperative agitation (restlessness, inability to cooperate with nursing care), dizziness; Others: Injection site pain, pruritus, paresthesia (recorded if persistent for ≥24 hours postoperatively).	Within 24 hours postoperatively (assessed during ward rounds or follow-up).

Collaborators and Investigators

• Sponsor: Ya-Qun Zhou
• Investigators: Principal Investigator: Ya-Qun Zhou, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: December 18, 2025
• First Submitted That Met QC Criteria: December 31, 2025
• First Posted (Estimated): January 12, 2026

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Spinal Anesthesia; Elderly Patients; Fospropofol Disodium; Lower Extremity Surgery; Adjunctive Sedation; 95% Effective Dose
• Additional Relevant MeSH Terms: fospropofol
• Other Study ID Numbers: LBFED95

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No