COnventional Vs. Optimised PERiprocedural Analgosedation Vs. Total IntraVEnous Anaesthesia for Pulsed-Field Ablation (COOPERATIVE-PFA)

Conventional Vs. Optimised Periprocedural Analgosedation Vs. Total Intravenous Anaesthesia for Pulsed-field Ablation: a Randomised Controlled Trial

A prospective single blinded (subject blinded) 1:1:1 randomised control trial with three parallel arms testing superiority of analgosedation regimen based on remimazolam and total intravenous anesthesia over propofol based analgosedation. The primary composite endpoint consists of hypoxaemia, hypotension, or hypertension requiring intervention.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Propofol; Drug: Propofol; Drug: Remimazolam

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 10034
    • University Hospital Královské Vinohrady

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Atrial fibrillation (AF) (paroxysmal, persistent or long standing persistent) with indication for catheter ablation
• Age above 18 years
• Capacity to give informed consent

Exclusion Criteria:

• Heart failure (NYHA III-IV), irrespective of left ventricular ejection fraction
• Left ventricular ejection fraction < 20%
• Significant valvulopathy (moderate or severe aortic stenosis, severe mitral regurgitation, severe aortic regurgitation, moderate and severe mitral stenosis, severe tricuspid regurgitation)
• Obstructive sleep apnoea syndrome (AHI >30)
• Low oxygen saturation (<93%) at baseline
• High aspiration risk (hiatal hernia, gastroesophageal reflux disease on chronic pharmacotherapy)
• Hypersensitivity to the study drugs
• Chronic kidney disease (stage 4 and 5 of CKD), liver cirrhosis
• Anticipated difficult airways
• ASA (American Society of Anaesthesiologists) score > 4
• Schizophrenia
• Epilepsy
• Other individual contraindications (will be reported in detail)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm P; Patients in arm P will be administered 2-3 mg midazolam IV before the beginning of the procedure, 5-10 mcg sufentanil IV and a loading dose of propofol 0,8-1,0 mg/kg in 2-5 minutes before the start of the ablation phase. During the procedure, boluses of 0,5 mg/kg propofol will be repeated as needed, in case of inappropriate analgosedation, boluses of midazolam and/or sufentanil can also 0be repeated.	Drug: Propofol; analgosedation with secured airway; Drug: Propofol; TIVA with secured airway
Experimental: Arm R; Patients in arm R will be administered 2,5 mg loading dose of remimazolam followed by continuous infusion at 0,5 mg/h/kg of ideal body weight (IBW, calculated using the Miller formula) and a dose of ketamine 1 mg/kg IBW 2-5 minutes before the beginning of the ablation phase. In case of inadequate sedation depth, a bolus of 2,5 mg remimazolam can be repeated as needed. If the patient shows signs of pain or discomfort, a single dose of ketamine - 0,5 mg/kg IBW - will be administered, followed by a bolus of 5-10 mcg sufentanil if needed. The continuous infusion will be terminated as the last ablation pulses are delivered.	Drug: Remimazolam; analgosedation without secured airway
Active Comparator: Arm TIVA (Total Intravenous Anesthesia); Patients randomised in arm TIVA will be administered light analgosedation with spontaneous ventilation for the first part of the procedure. The analgosedation will be induced and maintained with bolus of 5 mcg sufentanil IV and propofol infusion dosed by TCI system (the target plasma concentration for propofol 1-2 mcg/ml). Before the beginning of the ablation phase, general anesthesia will be induced with one bolus of 5-10 mcg sufentanil (the TCI target 3-7 mcg/ml for induction and 3-5 mcg/ml for the rest of the procedure), and a bolus of rocuronium 0,2-0,4 mg/kg IBW. Then, the airways will be secured with a laryngeal mask (LMA), the patient ventilated (0,4 - 0,45 FiO2, the target EtCO2 30 - 45 mmHg). After the last ablation pulse is delivered, infusion of propofol will be ceased and LMA extracted at the return of consciousness, muscle strength and sufficient spontaneous ventilation. If residual muscle relaxation occurs, sugammadex will be administered.	Drug: Propofol; analgosedation with secured airway; Drug: Propofol; TIVA with secured airway

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary composite endpoint (rate of hypoxaemia, hypotension, or hypertension events)	Composite endpoint consisting of the rate of (1) hypoxaemia events requiring intervention, (2) hypotension events requiring intervention or leading to the procedure interruption, or (3) hypertension events requiring intervention	Procedure duration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of haemodynamic instability events (hypoxemia, hypotension, hypertension; defined above), each five minutes of a continuous instability counts as a new event, as well as an instability persisting despite an intervention		Procedure duration
Total number of interventions a) jaw thrust b) nasopharyngeal airway administration c) LMA / orotracheal intubation d) increasing FiO2 (oxygen flow) e) hypotensive drugs administration f) vasoactive drugs administration (ephedrine, noradrenaline)		Procedure duration
Total procedural time		Procedure duration
Analgosedation depth by bispectral (BIS) monitoring: area under the curve of BIS index (measured every 3 minutes during the procedure)		Procedure duration
Procedural sedation quality	PROcedural Sedation Assessment Survey - a previously validated form	12-24 hours after the procedure
Difficult sedation score	1-10 scale (10 = the worst), reported by an anaesthesiologist	Procedure duration
Operator's satisfaction score	1-10 scale (10 = the worst), reported by the operating physician	Procedure duration
Total number of serious adverse events	death, cardiopulmonary resuscitation (chest compression or adrenaline administration), an emergency intubation or prolonged stay in intensive care unit	From randomization until discharge
carbon dioxide partial pressure after the procedure	partial pressure (kPa) of CO2 measured in an arterial blood sample	blood sample taken after the procedure (up to 10 minutes)
Total number of: a) hypoxemia events hypoxaemia <85% (more than 60s) b) hypotension events = systolic blood pressure (SBP) < 85 mmHg (more than 60s) c) hypertension event = SBP > 200 mmHg (more than 60s)		Procedure duration
28-day serious adverese events	death, a condition related to the procedure requiring inpatient hospitalization	discharge to the day 28

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2023
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: August 17, 2023
• First Submitted That Met QC Criteria: August 25, 2023
• First Posted (Actual): August 28, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 30, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Remimazolam; Pulsed field ablation; Analgosedation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Propofol
• Other Study ID Numbers: Coopertaive-PFA

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