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

Sponsor

Charles University, Czech Republic (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06013345

Collaborator

(none)

126

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: Remimazolam Drug: Propofol Drug: Propofol	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

126 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Study arms, analgosedation and TIVA protocols: 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 Optimised continuous intravenous analgosedation (arm R): ultrashort-acting benzodiazepine (remimazolam) and ketamine with unsecured airway Total intravenous anaesthesia with secured airway (arm TIVA): continuous propofol infusion using target controlled infusion (TCI) and short acting opioid boluses - sufentanilStudy arms, analgosedation and TIVA protocols: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 Optimised continuous intravenous analgosedation (arm R): ultrashort-acting benzodiazepine (remimazolam) and ketamine with unsecured airway Total intravenous anaesthesia with secured airway (arm TIVA): continuous propofol infusion using target controlled infusion (TCI) and short acting opioid boluses - sufentanil

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm P Patients in arm P will be administered 2-3 mg midazolam i.v. before the beginning of the procedure, 5-10 mcg sufentanil i.v. 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 be repeated.	Drug: Propofol analgosedation 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 (ideal body weight) 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. In case 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 infusion will be stopped as the last ablation pulses are delivered	Drug: Remimazolam analgosedation without secured airway
Experimental: Arm TIVA (Total Intravenous Anesthesia) General anaesthesia in patients randomised in arm TIVA will be induced and maintained with a bolus of 10 mcg sufentanil and propofol dosed by TCI system, model Schneider (plasma effect setting). The target plasma concentration for propofol will be set at 5-8 mcg/ml at induction and 4-6 mcg/ml for the rest of the procedure. After the induction, a laryngeal mask (LMA) will be inserted, the patient will be ventilated with 0,3 - 0,4 fraction of inspired oxygen (FiO2), minute ventilation set to achieve end tidal CO2 30 - 40 mmHg. At the beginning of the ablation phase, one bolus of 5-10 mcg sufentanil can be repeated. The dosage of TIVA can be changed so that no sign of discomfort is observed in the patient during ablation pulses. After the last ablation pulse is delivered, infusion of propofol will be ceased and LMA extracted at the return of consciousness.	Drug: Propofol TIVA with secured airway

Arm

Intervention/Treatment

Active Comparator: Arm P

Patients in arm P will be administered 2-3 mg midazolam i.v. before the beginning of the procedure, 5-10 mcg sufentanil i.v. 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 be repeated.

Drug: Propofol

analgosedation 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 (ideal body weight) 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. In case 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 infusion will be stopped as the last ablation pulses are delivered

Drug: Remimazolam

analgosedation without secured airway

Experimental: Arm TIVA (Total Intravenous Anesthesia)

General anaesthesia in patients randomised in arm TIVA will be induced and maintained with a bolus of 10 mcg sufentanil and propofol dosed by TCI system, model Schneider (plasma effect setting). The target plasma concentration for propofol will be set at 5-8 mcg/ml at induction and 4-6 mcg/ml for the rest of the procedure. After the induction, a laryngeal mask (LMA) will be inserted, the patient will be ventilated with 0,3 - 0,4 fraction of inspired oxygen (FiO2), minute ventilation set to achieve end tidal CO2 30 - 40 mmHg. At the beginning of the ablation phase, one bolus of 5-10 mcg sufentanil can be repeated. The dosage of TIVA can be changed so that no sign of discomfort is observed in the patient during ablation pulses. After the last ablation pulse is delivered, infusion of propofol will be ceased and LMA extracted at the return of consciousness.

Drug: Propofol

TIVA with secured airway

Outcome Measures

Primary Outcome Measures

Primary composite endpoint (rate of hypoxaemia, hypotension, or hypertension events) [Procedure duration]
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

Secondary Outcome Measures

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 30s) b) hypotension events = systolic blood pressure (SBP) < 85 mmHg (more than 30s) c) hypertension event = SBP > 200 mmHg (more than 30s) [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 [12-24 hours after the procedure]
PROcedural Sedation Assessment Survey - a previously validated form
Difficult sedation score [Procedure duration]
1-10 scale (10 = the worst), reported by an anaesthesiologist
Operator's satisfaction score [Procedure duration]
1-10 scale (10 = the worst), reported by the operating physician
Total number of serious adverse events [From randomization until discharge]
death, cardiopulmonary resuscitation (chest compression or adrenaline administration), an emergency intubation or prolonged stay in intensive care unit
carbon dioxide partial pressure after the procedure [blood sample taken after the procedure (up to 10 minutes)]
partial pressure (kPa) of CO2 measured in an arterial blood sample

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 < 40%
Significant valvulopathy (moderate or severe aortic stenosis, severe mitral regurgitation, severe aortic regurgitation, moderate and severe mitral stenosis)
Tricuspid regurgitation velocity above 2.8m/s
Obstructive sleep apnoea syndrome
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)