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

Phase 4

Not yet recruiting

• Conditions: ECMO Treatment; ARDS (Acute Respiratory Distress Syndrome); ECMO and Acute MI; Respiratory Failure Patients Treated With ECMO; Shock, Cardiogenic
• Interventions: Drug: Ciprofol; Drug: Midazolam

• Registration Number: NCT06934811
• Lead Sponsor: First Affiliated Hospital of Wannan Medical College

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-29
• Status Verified: 2025-04
• Study First Submitted QC: 2025-04-12
• Last Update Submitted: 2025-04-12
• Study First Posted: 2025-04-18
• Last Update Posted: 2025-04-18
• Study Start: 2025-05-01
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

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

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ciprofol group	Ciprofol	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).
Midazolam group	Midazolam	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).

Primary Outcome Measures

Name	Time	Method
Composite Oxygenator Dysfunction	At Day 3 and Day 7 of ECMO support	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

Secondary Outcome Measures

Name	Time	Method
Oxygenator Transmembrane Pressure (TMP) Gradients	Daily from Day 1 to Day 7	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
Post-oxygenator Oxygenation Index (PaO₂/FiO₂ Ratio)	Daily from Day 1 to Day 7	The post-oxygenator PaO₂/FiO₂ ratio will be measured daily to evaluate oxygenator efficiency. A value \<200 mmHg indicates impaired oxygenation capacity.
Oxygenator Lifespan	Through ECMO weaning or Day 30, whichever comes first	Definition: Time (hours) from ECMO initiation to oxygenator replacement. Replacement Criteria: Meeting ≥2 composite dysfunction criteria.
Lipid Profile Changes	At 24 hours, 72 hours, and Day 7	Measure: Serum triglycerides (TG)
Plasma D-dimer Concentration (μg/mL)	At 24 hours, 72 hours, and Day 7 post-ECMO initiation.	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).
Incidence of delirium	At 24h post-sedation discontinuation
ECMO Pump Head Malfunction	During ECMO support (up to 30 days)	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)
Thromboembolic Events	From ECMO initiation until 48 hours after decannulation	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
ECMO Weaning Success	Through study completion (Day 30)	Definition: Successful decannulation without re-initiation of ECMO within 24 hours.
7-day mortality rate	At Day 7	All-cause death rate at Day 7 post-ECMO initiation.
28-day mortality rate	At Day 28	All-cause death rate at Day 28 post-ECMO initiation.
ICU Length of Stay (LOS)	Through hospital discharge, up to 90 days	Duration from ICU admission to discharge (days).
Duration of Mechanical Ventilation	From ECMO initiation to successful extubation (up to 28 days)	Measure: Time (hours) from intubation to sustained extubation (48 hours without reintubation).