Prevention of Atrial Fibrillation by Low-dose Landiolol Administration After Cardiac Surgery (LANDIPROTEC)
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|ClinicalTrials.gov Identifier: NCT04607122|
Recruitment Status : Recruiting
First Posted : October 29, 2020
Last Update Posted : November 29, 2021
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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||400 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
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.
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.
Continuous infusion of saline solution at the same rate as landiolol infusion.
Other Name: Sodium chloride 0.9%
- 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.
- 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.
- Day-30 POAF free days [ Time Frame: 30 days ]
- Need for cardioversion for POAF treatment [ Time Frame: 30 days ]
- Need for medical treatment for POAF treatment [ Time Frame: 30 days ]
- Delay between ICU admission and the first event of POAF [ Time Frame: 30 days ]
- Delay between the first event and the recidive of POAF [ Time Frame: 30 days ]
- Delay for discharge because of POAF event [ Time Frame: 30 days ]
- All-cause mortality [ Time Frame: 30 days ]
- In-ICU death [ Time Frame: 30 days ]
- In-hospital death [ Time Frame: 30 days ]
- Day-30 hospital free days [ Time Frame: 30 days ]Length of hospital stay
- Day-30 ICU free days [ Time Frame: 30 days ]Length of ICU stay
- Day-30 ventilator-free days [ Time Frame: 30 days ]
- Day-30 renal replacement therapy-free days [ Time Frame: 30 days ]
- 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
- 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.
- Total hospital cost [ Time Frame: 30 days ]Cost hospital stay
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
|Contact: Cécile Naudin, PhD||(+33) 1 46 41 50 firstname.lastname@example.org|
|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|
|Principal Investigator:||Julien Amour, MD, PhD||Hôpital Privé Jacques Cartier, Massy, France|
|Study Chair:||Pierre Squara, MD||CMC Ambroise Paré, Neuilly-sur-Seine, France|