Efficacy and Safety of Fospropofol Disodium Versus Propofol for Sedation in Mechanically Ventilated ICU Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of fospropofol disodium for injection compared to propofol for sedation in mechanically ventilated ICU patients.

Detailed Description
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This is a randomized, open-label, small sample study using fospropofol disodium and propofol for sedation in mechanically ventilated ICU patients. Subjects are randomized to different treatment groups (including 1 for fospropofol disodium and 1 for propofol). Remifentanil is co-administered with fospropofol or propofol. Efficacy and safety profiles of fospropofol disodium are to be evaluated.

Official Title
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Efficacy and Safety of Fospropofol Disodium Versus Propofol for Sedation in Mechanically Ventilated ICU Patients

Conditions
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Critical Illness

Intervention / Treatment
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* Drug: Fospropofol disodium for injection
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged >= 18 and <= 75 years; Endotracheal intubated; Patients currently on mechanical ventilation <= 96 hours and expected to be mechanically ventilated >= 24 hours; Demand for light/moderate sedation (a RASS score of -3 to 0). Exclusion Criteria: Informed Consent is unsigned； Participated in any other interventional research within 3 months; Tracheostomy; BMI <= 18 and >= 35 kilograms per square meter Pregnant; Lactant; Known or suspected allergy to various components of the study drug or to opioids and their salvage drugs, or other diseases (such as pancreatitis associated with hyperlipidemia) for which lipid emulsion should not be used; Patients who cannot be evaluated for RASS for various reasons (such as mental illness, acquired or congenital mental retardation, deafness, severe neuromuscular disease, Parkinson's disease, Huntington's disease, Alzheimer's disease, cerebrovascular disease, coma, or severe cognitive impairment due to structural diseases such as stroke, intracranial hemorrhage, head injury, malignancy, hypoxic brain injury, or cerebral edema); Patients with an expected survival period of less than 48 hours; Severe hepatic insufficiency (CTP score is 10-15 points); Chronic kidney disease (CKD grade 3 above); Unstable angina pectoris or acute myocardial infarction; Left ventricular ejection fraction <= 30%; Heart rate < 50bpm(intravenous pumping of isoproterenol <4ug/min, heart rate ≥50bpm may not be excluded); Type 2 second-degree or third-degree atrioventricular block (except those implanted a pacemaker); Two vasoconstrictors are used to maintain SBP above 90mmHg after sufficient fluid resuscitation; Myasthenia gravis; Patients with a history of drug abuse, drug abuse, alcohol abuse and long-term use of psychotropic drugs within 2 years before the screening period. Binge drinking is defined as regular drinking more than 14 times per week (1 time = 150ml of wine or 360ml of beer or 45ml of spirits);

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fospropofol disodium for injection<br>Fospropofol disodium continuous infusion to reach a RASS score of -3 to 0. Remifentanil continuous infusion of 4 to 9 ug/kg/h for analgesia.The dosage adjustment plan was determined by the attending physician. Whether to use other sedative drugs is up to the attending physician. | Drug: Fospropofol disodium for injection<br>* Fospropofol disodium for injection continuous infusion to reach a RASS score of -3 to 0. Remifentanil continuous infusion of 4 to 9 ug/kg/h for. The dosage adjustment plan was determined by the attending physician. Whether to use other sedative drugs is up to the attending physician.<br>* Other names: Remifentanil;|
| Active Comparator: propofol<br>Propofol continuous infusion to reach a RASS score of -3 to 0. Remifentanil continuous infusion of 4 to 9 ug/kg/h for analgesia. The dosage adjustment plan was determined by the attending physician. Whether to use other sedative drugs is up to the attending physician. | Drug: Propofol<br>* Propofol for injection continuous infusion to reach a RASS score of -3 to 0. Remifentanil continuous infusion of 4 to 9 ug/kg/h for. The dosage adjustment plan was determined by the attending physician. Whether to use other sedative drugs is up to the attending physician.<br>* Other names: Remifentanil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time spent reaching sedation goals | Proportion of RASS assessment time points for subjects meeting target sedation levels among all RASS assessment time points during study drug administration without rescue sedation. | Within 7 days of the study began | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive ventilator free time within 7 days | The time without invasive ventilation within 7 days of the study began | Within 7 days of the study began | 
| Rate of successful extubation within 7 days | The proportion of participants who experienced successful extubation within 7 days of the study began | Within 7 days of the study began | 
| Incidence of unexpected extubation | Incidence of all extubation not planned by the attending physician | Within 7 days of the study began | 
| Proportion of delirium in the ICU | Delirium as a percentage of all evaluable mental patients in the ICU | During ICU stay | 
| Non-ICU survival time within 28 days | The time of survival outside of ICU within 7 days of the study began | Within 28 days of the study began | 
| Case fatality rate within 28 days | After follow-up, the fatality rates of all enrolled patients (including those still in ICU, transferred out and discharge) within 28 days of the study began | Within 28 days of the study began | 
| Percentage of time spent that trial drug was discontinued due to adverse events | Percentage of time the trial drug was discontinued due to any adverse event suspected to be related to the trial drug | Within 7 days of the study began | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fospropofol, Propofol, Sedation, Intensive care unit