Ciprofol's Impact on Oxygenator Function in Extracorporeal Membrane Oxygenation (ECMO) Patients (CIP-OXY)

Evaluating the Impact of Ciprofol on Oxygenator Performance in Patients Undergoing Extracorporeal Membrane Oxygenation: A Single-Center Randomized Controlled Trial (CIP-OXY Study)

This study evaluates the safety and effectiveness of Ciprofol, a new sedative, in critically ill patients receiving Extracorporeal Membrane Oxygenation (ECMO), a life-support system for heart or lung failure. The investigation aims to:

Assess how Ciprofol affects the oxygenator, a critical ECMO component responsible for adding oxygen to blood.

Compare the safety of Ciprofol to midazolam, a commonly used sedative. Eligibility Criteria Adults aged 18 years or older. Patients receiving ECMO and mechanical ventilation for over 72 hours. Individuals requiring sedation for medical procedures. Study Protocol

Participants will be randomly assigned to one of two groups:

Ciprofol Group: Initial sedation dose of 0.1 mg/kg, adjusted as needed. Midazolam Group: Initial sedation dose of 0.05 mg/kg, adjusted as needed. Both groups will receive pain management with remifentanil. Sedation levels will be adjusted daily by the clinical team to ensure patient safety and comfort.

Outcome Measures Primary: Oxygenator performance (oxygen and carbon dioxide levels) on Days 3 and 7.

Secondary: Changes in blood triglyceride and clotting marker (D-dimer) levels, oxygenator lifespan before replacement, and safety outcomes such as low blood pressure, respiratory issues, or allergic reactions.

Significance ECMO patients often require prolonged sedation, but current sedatives like midazolam may contribute to oxygenator damage. Ciprofol's potential for faster recovery and fewer side effects could improve sedation practices and device longevity in this high-risk population.

Study Overview

• Status: Not yet recruiting
• Conditions: Shock, Cardiogenic; ECMO Treatment; ARDS (Acute Respiratory Distress Syndrome); ECMO and Acute MI; Respiratory Failure Patients Treated With ECMO
• Intervention / Treatment: Drug: Ciprofol; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Qiancheng Xu; Phone Number: 86-18297529106; Email: qianchengxu@wnmc.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

1. Inclusion Criteria:

   • Receiving ECMO therapy with an anticipated duration exceeding 72 hours;
   • Requiring invasive mechanical ventilation;
   • Requiring sedation and analgesia treatment.

2. Exclusion Criteria:

   • BMI >45 kg/m²;
   • Age <18 years;
   • Severe hepatic (Child-Pugh Class C) or renal failure (eGFR <15 mL/min/1.73m²);
   • History of severe psychiatric disorders;
   • Pregnancy;
   • Refusal to sign informed consent;
   • Contraindications to midazolam and propofol use.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ciprofol group; Patients in this arm will receive Ciprofol, an investigational sedative, administered via continuous intravenous infusion. Dosing Protocol: Initial Dose: 0.1 mg/kg loading dose over 1-2 minutes. Maintenance Dose: 0.05-0.3 mg/kg/h, adjusted hourly based on the Richmond Agitation-Sedation Scale (RASS) score (target range: -3 to 0). Combined Analgesia: All patients will concurrently receive remifentanil (0.05-0.3 μg/kg/min) for pain control. Monitoring & Adjustments: Sedation depth assessed every 30 minutes using RASS and ( Critical-Care Pain Observation Tool) CPOT scores. Dose adjustments made to avoid hypotension (Mean Arterial Pressure) MAP < 65 mmHg or oversedation. Triglyceride levels monitored daily to guide lipid emulsion management. Safety Measures: Rescue protocol for hypotension (e.g., vasopressors) or respiratory depression (e.g., temporary ECMO flow adjustment).	Drug: Ciprofol; Continuous intravenous infusion (0.05-0.3 mg/kg/h), adjusted hourly based on the RASS score (target range: -3 to 0).
Active Comparator: Midazolam group; Patients in this arm will receive midazolam, a benzodiazepine sedative commonly used in ECMO patients, administered via continuous intravenous infusion. Dosing Protocol: Initial Dose: 0.05 mg/kg loading dose over 2-5 minutes. Maintenance Dose: 0.02-0.1 mg/kg/h, adjusted hourly based on the RASS score (target range: -3 to 0). Combined Analgesia: All patients will concurrently receive remifentanil (0.05-0.3 μg/kg/min) for pain control, identical to the Ciprofol group. Monitoring & Adjustments: Sedation depth assessed every 30 minutes using RASS and CPOT scores, consistent with the experimental group. Dose adjustments made to avoid hypotension (MAP < 65 mmHg) or oversedation. Daily monitoring of drug accumulation markers (e.g., midazolam plasma levels if available). Safety Measures: Rescue protocol for hypotension (e.g., vasopressors) or respiratory depression (e.g., ventilator support escalation).	Drug: Midazolam; Continuous intravenous infusion (0.02-0.1 mg/kg/h), adjusted hourly based on the RASS score (target range: -3 to 0).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Oxygenator Dysfunction	Definition: Meeting ≥2 of the following: Post-oxygenator PaO₂/FiO₂ <200 mmHg ΔTransmembrane pressure (ΔdP) ≥20% from baseline or Transmembrane pressure (TMP)>50 mmHg from baseline CO₂ clearance <20% [(Pre-MLCO₂ - Post-MLCO₂)/Pre-MLCO₂] at gas flow ≥10 L/min	At Day 3 and Day 7 of ECMO support

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygenator Transmembrane Pressure (TMP) Gradients	Transmembrane pressure (TMP) will be assessed using continuous inline pressure monitoring via the ECMO circuit's integrated pressure sensors (e.g., pre- and post-oxygenator pressure transducers). TMP is calculated as: TMP (mmHg) = Post-oxygenator Pressure - Pre-oxygenator Pressure	Daily from Day 1 to Day 7
Post-oxygenator Oxygenation Index (PaO₂/FiO₂ Ratio)	The post-oxygenator PaO₂/FiO₂ ratio will be measured daily to evaluate oxygenator efficiency. A value <200 mmHg indicates impaired oxygenation capacity.	Daily from Day 1 to Day 7
Oxygenator Lifespan	Definition: Time (hours) from ECMO initiation to oxygenator replacement. Replacement Criteria: Meeting ≥2 composite dysfunction criteria.	Through ECMO weaning or Day 30, whichever comes first
Lipid Profile Changes	Measure: Serum triglycerides (TG)	At 24 hours, 72 hours, and Day 7
Plasma D-dimer Concentration (μg/mL)	Description: Absolute plasma D-dimer levels measured as a biomarker of hypercoagulability and thromboembolic risk. Threshold: >5 μg/mL (defined as high thrombotic risk per International Society on Thrombosis and Haemostasis [ISTH] guidelines).	At 24 hours, 72 hours, and Day 7 post-ECMO initiation.
Incidence of delirium		At 24h post-sedation discontinuation
ECMO Pump Head Malfunction	Definition: Occurrence of any of the following: Pump head rupture (visible crack or leak) Pump head thrombosis (ultrasound-confirmed thrombus within the pump housing) Mechanical failure (unplanned pump stoppage requiring emergency intervention)	During ECMO support (up to 30 days)
Thromboembolic Events	Definition: Radiologically confirmed: Arterial embolism: Cerebral or limb artery occlusion (CT angiography/ultrasound) Venous thrombosis: Lower extremity DVT or pulmonary embolism (CT pulmonary angiography/Doppler) Intracardiac thrombus: Echocardiographic or CT evidence Grading: Major: Life-threatening or requiring intervention (e.g., thrombectomy) Minor: Asymptomatic or managed medically	From ECMO initiation until 48 hours after decannulation
ECMO Weaning Success	Definition: Successful decannulation without re-initiation of ECMO within 24 hours.	Through study completion (Day 30)
7-day mortality rate	All-cause death rate at Day 7 post-ECMO initiation.	At Day 7
28-day mortality rate	All-cause death rate at Day 28 post-ECMO initiation.	At Day 28
ICU Length of Stay (LOS)	Duration from ICU admission to discharge (days).	Through hospital discharge, up to 90 days
Duration of Mechanical Ventilation	Measure: Time (hours) from intubation to sustained extubation (48 hours without reintubation).	From ECMO initiation to successful extubation (up to 28 days)

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Wannan Medical College

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 29, 2025
• First Submitted That Met QC Criteria: April 12, 2025
• First Posted (Actual): April 18, 2025

Study Record Updates

• Last Update Posted (Actual): April 18, 2025
• Last Update Submitted That Met QC Criteria: April 12, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; ECMO; Midazolam; Ciprofol; Sedative; Oxygenator function; Oxygenator thrombosis
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Shock; Lung Injury; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Shock, Cardiogenic; Acute Lung Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anesthetics; Central Nervous System Depressants; Neurotransmitter Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 202507

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
• product manufactured in and exported from the U.S.: No