Efficacy and Safety of Fospropofol for Same-day Bidirectional Endoscopy in Elderly Patients

Efficacy and Safety of Fospropofol Disodium Sedation for Same-day Bidirectional Endoscopy in Elderly Patients: a Prospective, Single-center, Randomized, Double-blind, Non-inferiority Trial

Introduction: Fospropofol disodium is a novel prodrug that has improved pharmacokinetic and pharmacodynamic properties compared with propofol. This trial aims to compare the efficacy and safety of fospropofol versus propofol sedation for same-day bidirectional endoscopy in elderly patients.

Methods and analysis: This is a prospective, single-center, double-blind, randomized, propofol-controlled, non-inferiority trial. A total of 256 adult patients scheduled for same-day bidirectional endoscopy under sedation will be randomly allocated, in a 1:1 ratio, to a fospropofol group or a propofol group (n=128 in each group). All patients will receive analgesic pretreatment with sufentanil 5 μg. Two minutes later, an initial bolus dose of fospropofol 6.5 mg/kg or 1.5 mg/kg propofol and supplemental doses of fospropofol 1.6 mg/kg or 0.5 mg/kg propofol will be titrated as needed to the target sedation levels during the procedures. The primary outcome is the success rate of same-day bidirectional endoscopy. Secondary outcomes include the time to successful induction of sedation, duration, time to being fully alert, time to patient discharge, endoscopist satisfaction, patient satisfaction, and the top-up frequency and dosage of sedative medications. The safety endpoints consist of adverse events (AEs) concerning cough reflex, gag reflexes, body movement, muscular tremor, pain on injection. Sedation-related AEs, including episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in mean blood pressure ≥30% of baseline), and bradycardia, will be also recorded. Data will be analyzed on the intention-to-treat basis.

Discussion: The investigators hypothesize that the efficacy and safety of fospropofol sedation for elderly patients undergoing same-visit bidirectional endoscopy will not be inferior to that of propofol. The findings will provide daily practice of sedation regimens for same-day bidirectional endoscopy in elderly patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Elderly Patients
• Intervention / Treatment: Drug: Propofol; Drug: fospropofol sedation

• Study Type: Interventional
• Enrollment (Estimated): 256
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 65 years or older
• American Society of Anesthesiologists (ASA) physical status I to III
• Body mass index (BMI) 18-30 kg/m2
• Scheduled for same-day bidirectional endoscopy under sedation

Exclusion Criteria:

• Severe cardiovascular, pulmonary, renal, or liver diseases
• Previous hypotension (systolic blood pressure ≤90 mmHg), bradycardia (heart rate <50 beats/min), or hypoxemia (SpO2 <90%)
• Neurocognitive or psychiatric disorders
• Contraindications to gastroscopy (gastric retention, long-term aspirin administration, etc.)
• Hypersensitivity to study medications
• Drug or alcohol misuse
• Definite upper respiratory tract infection
• Refusal for participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: propofol	Drug: Propofol; propofol
Experimental: fospropofol	Drug: fospropofol sedation; Fospropofol sedation for same-day bidirectional endoscopy in elderly patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The success rate of same-day bidirectional endoscopy	The success rate of the gastrointestinal endoscopy was assessed according to the following criteria : 1) completion of the gastrointestinal endoscopy; 2) no need for rescue sedative/anesthetic, which means the top-up doses of the experimental drugs were administered no more than five times within any 15-min window from the initial administration to the end of the procedure.	Immediate time after sedation emergence

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time to successful induction of sedation	the time counted from the start of drug administration to the achievement of a sedation score (MOAA/S ) ≤ 1	Immediate time after sedation emergence
Time to being fully alert	the time from gastrointestinal endoscopy extraction or/and the time from the last drug administration to a MOAA/S score of 5 on three consecutive measurements;	Immediate time after sedation emergence
Time to patient discharge	Time to patient discharge	Immediate time of hospital discharge
Endoscopist's satisfaction questionnaire	Endoscopist's satisfaction	Immediate time after sedation procedure completion
Patient's satisfaction questionnaire	Patient's satisfaction	Immediate time of hospital discharge
The top-up frequency and dosage of sedative medications	The top-up frequency and dosage of sedative medications	Immediate time after sedation emergence
Incidence of adverse events (AEs) at timepoint 1	Episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in mean blood pressure ≥30% of baseline), and bradycardia.	baseline (Prior to sedation)
Incidence of adverse events (AEs) at timepoint 2	Episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in mean blood pressure ≥30% of baseline), and bradycardia.	Intraoperative (during sedation)
Incidence of adverse events (AEs) at timepoint 3	Episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in mean blood pressure ≥30% of baseline), and bradycardia.	Intraoperative (the timepoint of sedation emergence)
Incidence of adverse events (AEs) at timepoint 4	Episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in mean blood pressure ≥30% of baseline), and bradycardia.	15 min in post-anesthesia care unit
Incidence of adverse events (AEs) at timepoint 5	Episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in mean blood pressure ≥30% of baseline), and bradycardia.	30 min in post-anesthesia care unit
Incidence of adverse events (AEs) at timepoint 6	Episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in mean blood pressure ≥30% of baseline), and bradycardia.	Immediate time of hospital discharge

Collaborators and Investigators

• Sponsor: Shanghai 6th People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: January 21, 2024
• First Submitted That Met QC Criteria: February 8, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: elderly; sedation; propofol; bidirectional endoscopy; fospropofol
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol; Fospropofol
• Other Study ID Numbers: XWANG

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