RePAF: Remimazolam for Postoperative Atrial Fibrillation

Sponsor

Yangzhou University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05891145

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Bypass Grafting Remimazolam	Drug: Remimazolam Drug: midazolam	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Masking Description:

The random numbers will be generated by the Power Analysis and Sample Site Software 9.0 (PASS 9.0), sealed with envelopes, and assigned in the order of enrollment by researchers. The randomized envelopes shall only be opened before anesthesia and resealed right after the operation. Unblinding of results: the monitoring committee did the data unblinding after all enrollment, follow-up, and data entry. Unblinded data was limited to the data monitoring committee and statistical analysts. Patients can have emergency unblinding under the following conditions: 1) serious adverse events; 2) The result of the unblinding was needed for the following treatment. 3) other emergency situations that investigators thought necessary for unblinding, the detailed reasons need to be recorded.

Primary Purpose:

Treatment

Official Title:

The Effect of Remimazolam on Postoperative New-onset Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting

Actual Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Remimazolam group General anesthesia was induced with 0.1 mg/kg of remimazolam and maintained with 0.1 mg•kg-1•h-1 remimazolam.	Drug: Remimazolam Remimazolam is dispensed at 2 mg/ml by the designated researchers who are not involved in enrollment, anesthesia administration, and postoperative follow-up.
Active Comparator: Control group General anesthesia was induced with 0.1 mg/kg midazolam.	Drug: midazolam Midazolam is dispensed at 1 mg/ml by the designated researchers who are not involved in enrollment, anesthesia administration, and postoperative follow-up.

Arm

Intervention/Treatment

Experimental: Remimazolam group

General anesthesia was induced with 0.1 mg/kg of remimazolam and maintained with 0.1 mg•kg-1•h-1 remimazolam.

Drug: Remimazolam

Remimazolam is dispensed at 2 mg/ml by the designated researchers who are not involved in enrollment, anesthesia administration, and postoperative follow-up.

Active Comparator: Control group

General anesthesia was induced with 0.1 mg/kg midazolam.

Drug: midazolam

Midazolam is dispensed at 1 mg/ml by the designated researchers who are not involved in enrollment, anesthesia administration, and postoperative follow-up.

Outcome Measures

Primary Outcome Measures

postoperative Atrial Fibrillation (POAF) [7 days after the operation.]
POAF is defined as postoperative new-onset Atrial Fibrillation (AF) lasting more than the 30 s or hemodynamic instability requiring treatment. AF is defined as 1) irregular R-R interval (in the presence of AV conduction), 2) P-wave disappearance, and 3) irregular atrial activity according to the AHA guidelines.

Secondary Outcome Measures

Inflammatory factors [1) immediately after the operation, 2) 24 hours after the operation.]
Blood level of TNF-α
Stress factors [1) immediately after the operation, 2) 24 hours after the operation.]
Blood level of epinephrine, norepinephrine, cortisol, adrenocorticotropic hormone, corticotropin-releasing hormone.

Other Outcome Measures

Myocardial injury markers [7 days after the operation.]
Myocardial injury markers (cTnT, cTnI, CK-MB)
Arterial blood pressure (BP) [7 days after the operation.]
Hemodynamic parameters
Cardiac index (CI) [7 days after the operation.]
Hemodynamic parameters
systemic vascular resistance (SVR) [7 days after the operation.]
Hemodynamic parameters
stroke volume variation (SVV) [7 days after the operation.]
Hemodynamic parameters

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.