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

NCT06013345 | Completed Phase 3

• 1 other identifier: Coopertaive-PFA
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atrial Fibrillation

Keywords

Analgosedation; Remimazolam; Atrial Fibrillation; Pulsed field ablation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• 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: 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

• 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

Study Arms (3)

Arm P

ACTIVE COMPARATOR

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

Arm R

EXPERIMENTAL

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

Arm TIVA (Total Intravenous Anesthesia)

ACTIVE COMPARATOR

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

Interventions

Remimazolam DRUG

analgosedation without secured airway

Arm R

Propofol DRUG

analgosedation with secured airway

Arm P

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Charles University, Czech Republic: lead

Study Sites (1)

University Hospital Kralovske Vinohrady

Prague, Czechia, 10034, Czechia

Location

Related Publications (1)

• Sochorova V, Kunstatova V, Osmancik P, Duska F, Herman D, Waldauf P, Poviser L, Karch J, Znojilova L, Filipcova V, Hozmanova J, Vesela J, Hozman M. COOPERATIVE-PFA: A Three-Arm Randomized Controlled Trial. Circulation. 2025 Jul 22;152(3):150-159. doi: 10.1161/CIRCULATIONAHA.125.074427. Epub 2025 Apr 27.

  PMID: 40287932 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

remimazolam; Propofol

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Study arms, analgosedation and TIVA protocols: 1. Conventional propofol analgosedation (arm P): current standard practice in most centres, a combination of short-acting benzodiazepine (midazolam) at the beginning, short-acting opioid (sufentanil in this study) and propofol boluses before and during the application of ablation pulses with unsecured airway 2. Optimised continuous intravenous analgosedation (arm R): ultrashort-acting benzodiazepine (remimazolam) and ketamine with unsecured airway 3. Total intravenous anaesthesia with secured airway (arm TIVA): continuous propofol infusion using target controlled infusion (TCI) and short acting opioid boluses - sufentanil

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: August 28, 2023
• Study Start: October 25, 2023
• Primary Completion: September 30, 2024
• Study Completion: December 1, 2024
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

CZ (1)