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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04607122
Recruitment Status : Recruiting
First Posted : October 29, 2020
Last Update Posted : November 29, 2021
Sponsor:
Information provided by (Responsible Party):
CMC Ambroise Paré

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.


Condition or disease Intervention/treatment Phase
Atrial Fibrillation Cardiac Surgery Drug: Landiolol Drug: Saline Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Interest of Low-dose Landiolol Administration After Cardiac Surgery for the Prevention of Postoperative Atrial Fibrillation
Actual Study Start Date : January 27, 2021
Estimated Primary Completion Date : July 27, 2023
Estimated Study Completion Date : August 28, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Landiolol group
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
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.
Other Name: Rapibloc

Placebo Comparator: Placebo group
Saline solution infusion administrated after the surgery, on arrival at the ICU, until restoration of an effective oral beta-blocker treatment.
Drug: Saline
Continuous infusion of saline solution at the same rate as landiolol infusion.
Other Name: Sodium chloride 0.9%




Primary Outcome Measures :
  1. POAF occurrence in Intensive Care Unit (ICU) [ Time Frame: 7 days ]
    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.


Secondary Outcome Measures :
  1. Duration of POAF episode [ Time Frame: 30 days ]
    Duration (in hours) of POAF episode categorized into five groups: POAF < 6h, POAF sustained ≥ 6h, POAF sustained ≥ 12h, POAF sustained ≥ 24h and POAF sustained ≥ 48h.

  2. Day-30 POAF free days [ Time Frame: 30 days ]
  3. Need for cardioversion for POAF treatment [ Time Frame: 30 days ]
  4. Need for medical treatment for POAF treatment [ Time Frame: 30 days ]
  5. Delay between ICU admission and the first event of POAF [ Time Frame: 30 days ]
  6. Delay between the first event and the recidive of POAF [ Time Frame: 30 days ]
  7. Delay for discharge because of POAF event [ Time Frame: 30 days ]
  8. All-cause mortality [ Time Frame: 30 days ]
  9. In-ICU death [ Time Frame: 30 days ]
  10. In-hospital death [ Time Frame: 30 days ]
  11. Day-30 hospital free days [ Time Frame: 30 days ]
    Length of hospital stay

  12. Day-30 ICU free days [ Time Frame: 30 days ]
    Length of ICU stay

  13. Day-30 ventilator-free days [ Time Frame: 30 days ]
  14. Day-30 renal replacement therapy-free days [ Time Frame: 30 days ]
  15. Occurrence of major cardiovascular events [ Time Frame: 30 days ]
    Cardiogenic shock, stroke or transient ischemic attack, seizure, cardiac arrest, myocardial infarction, Reoperation for bleeding, All-cause bleeding

  16. Occurrence of drug adverse events [ Time Frame: 7 days ]
    Bradycardia: HR < 50 bpm requiring heart pacing, Atrio-ventricular block requiring pacing, Severe hypotension: MAP < 50 mmHg requiring discontinuation of the protocol and specific treatment, Major ventricular arrhythmia requiring cardioversion.

  17. Total hospital cost [ Time Frame: 30 days ]
    Cost hospital stay



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Preoperative Exclusion Criteria:

  • 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 Exclusion Criteria:

- 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).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04607122


Contacts
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Contact: Cécile Naudin, PhD (+33) 1 46 41 50 79 recherche@clinique-a-pare.fr

Locations
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France
Hôpital Privé Jacques Cartier Recruiting
Massy, France, 91300
Contact: Julien Amour, MD, PhD         
Principal Investigator: Julien Amour, MD, PhD         
CMC Ambroise Paré Recruiting
Neuilly-sur-Seine, France, 92200
Contact: Philippe Estagnasié, MD         
Principal Investigator: Philippe Estagnasié, MD         
Sponsors and Collaborators
CMC Ambroise Paré
Investigators
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Principal Investigator: Julien Amour, MD, PhD Hôpital Privé Jacques Cartier, Massy, France
Study Chair: Pierre Squara, MD CMC Ambroise Paré, Neuilly-sur-Seine, France
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Responsible Party: CMC Ambroise Paré
ClinicalTrials.gov Identifier: NCT04607122    
Other Study ID Numbers: 2019/10
2019-004829-25 ( EudraCT Number )
First Posted: October 29, 2020    Key Record Dates
Last Update Posted: November 29, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by CMC Ambroise Paré:
Postoperative atrial fibrillation
Cardiac surgery
Landiolol hydrochloride
Low dose
Prophylactic administration
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Landiolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents