Prevention of Atrial Fibrillation by Low-dose Landiolol Administration After Cardiac Surgery

NCT04607122 | Completed Phase 3

• 2 other identifiers: 2019/102019-004829-25
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 3

Brief Summary

Postoperative atrial fibrillation (POAF) is a common complication that occurs in 30-50% of patients after cardiac surgery and increases morbidity and mortality and hospital length of stay. During the perioperative period, the discontinuation of beta-blocker treatment is known to be a risk factor for developing POAF in patient undergoing cardiac surgery. Early beta-blocker reintroduction is associated with lower incidence of POAF. Unfortunately, side effects of currently available beta-blockers (including esmolol), such as low blood pressure and excessive bradycardia and/or their extended duration of action, limit their use in the post-operative period especially for prevention. Landiolol, an ultra-short acting injectable beta-blocker, offers the advantage of significantly limiting low blood pressure events while increasing therapeutic efficacy in the treatment of POAF in cardiac and non-cardiac surgery. Landiolol, when used at low dose in the postoperative period, has been showed to reduce the incidence of POAF with no increased incidence of side effect as compared to standard of care. The limitation is that these promising data come from single center studies with limited samples and conducted exclusively in Japanese population. If landiolol is approved for use in the treatment of atrial fibrillation in non-Asian patients, there are no data on the prevention of POAF in cardiac surgery. The objective of this multicenter, double-blind, randomized, placebo- controlled phase III trial is to confirm that landiolol postoperative infusion is associated with lower incidence of POAF without excess of adverse events as compared to standard of care in a non-Asian population after cardiac surgery with sternotomy.

Conditions

Atrial Fibrillation; Cardiac Surgery

Keywords

Postoperative atrial fibrillation; Cardiac surgery; Landiolol hydrochloride; Low dose; Prophylactic administration

Outcome Measures

Primary Outcomes (1)

• POAF occurrence in Intensive Care Unit (ICU)

  POAF event occurring from arrival to departure of the ICU assessed by continuous monitoring of heart rate (HR). POAF is defined as the occurrence of atrial fibrillation de novo, lasting more than 5 minutes (on the systematic reading of telemetry) and/or requiring specific medical treatment and/or cardioversion.

  7 days

Secondary Outcomes (17)

• Duration of POAF episode

  30 days

• Day-30 POAF free days

  30 days

• Need for cardioversion for POAF treatment

  30 days

• Need for medical treatment for POAF treatment

  30 days

• Delay between ICU admission and the first event of POAF

  30 days

Study Arms (2)

Landiolol group

EXPERIMENTAL

Landiolol infusion (2µg/kg/min) administrated after the surgery, on arrival at the ICU, until restoration of an effective oral beta-blocker treatment.

Drug: Landiolol

Placebo group

PLACEBO COMPARATOR

Saline solution infusion administrated after the surgery, on arrival at the ICU, until restoration of an effective oral beta-blocker treatment.

Drug: Saline

Interventions

Landiolol DRUG

Continuous infusion of landiolol starting at 1 µg/kg/min and increasing every 10-15 minutes with incremental doses of 0.5 µg/kg/min up to 2 µg/kg/min by maintaining MAP ≥ 65 mmHg and HR ≥ 50/min.

Also known as: Rapibloc

Landiolol group

Saline DRUG

Continuous infusion of saline solution at the same rate as landiolol infusion.

Also known as: Sodium chloride 0.9%

Placebo group

Eligibility Criteria

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

You may qualify if:

• Non-Asian,
• Undergoing cardiac surgery with CPB,
• Left ventricular ejection fraction (LVEF) ≥ 40%,
• Having signed a written informed consent form,
• Affiliation to the social security system.

You may not qualify if:

• Paroxystic or persistant atrial fibrillation before surgery,
• Preoperative contraindication to beta-blockers,
• Known hypersensitivity to landiolol,
• Severe conduction disorders (atrio-ventricular conduction block),
• A mental or linguistic inability to understand the study,
• Dying patient,
• Patient under protection of the adults (guardianship, curators or safeguard of justice),
• Patient included or planning to be included in another research protocol relating to medications.
• \- Postoperative contraindication to beta-blockers: severe sinus bradycardia requiring pacing, postcardiotomy low cardiac output requiring inotropic agents (noradrenaline being not considered as an inotropic agent), severe hypotension, severe acute pulmonary hypertension, reoperation for significant bleeding (\> 200 ml/h), acute respiratory distress syndrome defined by increased oxygen dependence, a PaO2/FiO2 ratio \< 200, polypnea \> 30 /min, signs of respiratory distress (retractions, thoraco-abdominal asynchrony).

Sponsors & Collaborators

• CMC Ambroise Paré: lead

Study Sites (3)

Hôpital Privé Jacques Cartier

Massy, 91300, France

Location

CMC Ambroise Paré

Neuilly-sur-Seine, 92200, France

Location

Centre Cardiologique du Nord

Saint-Denis, 93200, France

Location

Related Publications (1)

• Amour J, Naudin C, Besnard A, Merzoug M, Laverdure F, Frossard B, Morichau-Beauchant T, Geri G, Squara P. Low dose of landiolol does not prevent postoperative atrial fibrillation after cardiac surgery in non-Asian patients: a multicentre randomised study. Br J Anaesth. 2026 Jan;136(1):65-73. doi: 10.1016/j.bja.2025.09.019. Epub 2025 Nov 6.

  PMID: 41203473 RESULT

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

landiolol; Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Julien Amour, MD, PhD

  Hôpital Privé Jacques Cartier, Massy, France

  PRINCIPAL INVESTIGATOR

• Pierre Squara, MD

  CMC Ambroise Paré, Neuilly-sur-Seine, France

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2020
• First Posted: October 29, 2020
• Study Start: January 27, 2021
• Primary Completion: June 30, 2023
• Study Completion: July 22, 2023
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)