Clinical trial NCT05891145: Remimazolam for Postoperative Atrial Fibrillation
Official title: The Effect of Remimazolam on Postoperative New-onset Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coronary Artery Bypass Grafting
Remimazolam
Keywords: Remimazolam
CABG
Postoperative atrial fibrillation
Postoperative new-onset atrial fibrillation
Coronary artery disease
CAD
Coronary artery bypass graft
Myocardial infarction
Revascularization
Anesthesia
Ischemic heart disease
Lead sponsor: Yangzhou University
Sponsor class: OTHER
First posted: 2023-06-06
Enrollment: 50
Sex: ALL
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A first open-phase trial in which 50 patients (randomized 1:1 to Remimazolam and control groups) will be enrolled as a pilot study to obtain parameters for sample size calculation. A double-blind randomized controlled trial will be conducted to explore remimazolam's effect on POAF and inflammatory factors' blood levels in patients that receive selective CABG.
Primary purpose: TREATMENT

Brief summary: Atrial fibrillation (AF) is the most common cardiac severe arrhythmia globally and is associated with an increased risk of mortality and morbidity, with a loss of 6.0 million disability-adjusted life-years worldwide in 2017, conferring 0.24% of total disability-adjusted life-years globally. Due to the absence of knowledge of AF pathogenesis, currently, available therapies do not prevent AF onset or progression in 85% of patients. Despite the identification of novel druggable targets that are involved in the pathogenesis of AF, the translation of these findings to clinical drug studies is limited.

Postoperative atrial fibrillation (POAF) is the most common type of secondary AF. The incidence of POAF after coronary artery bypass grafting (CABG) is approximately 30%. About 16% of patients developed POAF in cardiac surgery even with the international guideline recommended perioperative beta-blocker intervention.

Remimazolam is a newly approved benzodiazepine sedative indicated for the induction and maintenance of procedural sedation in adults, with significantly reduced sedation and recovery time. It was also found to be with an anti-inflammatory effect and therefore might have an impact on POAF since AF is closely related to the inflammatory response of myocardial tissue and inflammatory factors such as TNF-α. So, the RePAF trial intends to explore whether remimazolam application in induction and maintenance for general anesthesia during cardiac surgery can reduce the incidence of POAF in patients with CABG, and the effect on the postoperative plasma levels of inflammatory factors and stress factors.

Detailed description: Postoperative atrial fibrillation (POAF) presented a 30% incidence in cardiac surgery and 16% even under beta-blocker treatment, leading to serious complications. Inflammation is a key mechanism that promotes POAF. Remimazolam is a newly approved benzodiazepine sedative with anti-inflammatory effects. However, the impact of remimazolam on POAF remains unknown.

To explore whether or not remimazolam can reduce the POAF in coronary artery bypass grafting (CABG) patients, a first open-phase trial in which 50 patients (randomized 1:1 to Remimazolam and control groups) will be enrolled as a pilot study to obtain parameters for sample size calculation. A double-blind randomized controlled trial will be then conducted to explore remimazolam's effect on POAF and inflammatory factors' blood levels in patients that receive selective CABG.

The blood level of inflammatory factors, stress factors (epinephrine, norepinephrine, cortisol, adrenocorticotropic hormone, corticotropin-releasing hormone), myocardial injury markers, and hemodynamic parameters will also be assessed.

This 2-phase clinical trial will provide novel evidence for the newly approved sedative drug, remimazolam, and with detailed data for inflammatory and myocardial injury endpoints.

Eligibility criteria: Inclusion Criteria:

* 50-70 years old;
* BMI 18-28 kg/m2；
* Selective CABG surgery will be performed at the Yangzhou Institute Heart and Great Vessels, the Affiliated Hospital of Yangzhou University, Yangzhou, China.
* Patients agree to participate in this study and sign the informed consent form.

Exclusion Criteria:

* Emergency surgery;
* with any other type of cardiac surgery;
* pre-operative supraventricular arrhythmia;
* with moderate or severe valve disease before surgery;
* with a history of chemotherapy or radiotherapy;
* with a history of thoracic or cardiovascular surgery;
* diuretics usage before the surgery.

Primary outcomes:
measure: postoperative Atrial Fibrillation (POAF)
timeFrame: 7 days after the operation.
Secondary outcomes:
measure: Inflammatory factors
timeFrame: 1) immediately after the operation, 2) 24 hours after the operation.
measure: Stress factors
timeFrame: 1) immediately after the operation, 2) 24 hours after the operation.
Other outcomes:
measure: Myocardial injury markers
timeFrame: 7 days after the operation.
measure: Arterial blood pressure (BP)
timeFrame: 7 days after the operation.
measure: Cardiac index (CI)
timeFrame: 7 days after the operation.
measure: systemic vascular resistance (SVR)
timeFrame: 7 days after the operation.
measure: stroke volume variation (SVV)
timeFrame: 7 days after the operation.
Locations:
city: Yangzhou
country: China
facility: The Affiliated Hospital of Yangzhou University.
state: Jiangsu
Study officials:
References: