Remimazolam for Postoperative Atrial Fibrillation

NCT05891145 | Recruiting DMC

• 1 other identifier: 2023-YKL01-16
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• postoperative Atrial Fibrillation (POAF)

  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.

  7 days after the operation.

Secondary Outcomes (2)

• Inflammatory factors

  1) immediately after the operation, 2) 24 hours after the operation.

• Stress factors

  1) immediately after the operation, 2) 24 hours after the operation.

Other Outcomes (5)

• Myocardial injury markers

  7 days after the operation.

• Arterial blood pressure (BP)

  7 days after the operation.

• Cardiac index (CI)

  7 days after the operation.

Study Arms (2)

Remimazolam group

EXPERIMENTAL

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

Drug: Remimazolam

Control group

ACTIVE COMPARATOR

General anesthesia was induced with 0.1 mg/kg midazolam.

Drug: midazolam

Interventions

Remimazolam DRUG

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

Remimazolam group

midazolam DRUG

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

Control group

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yangzhou University: lead

Study Sites (1)

The Affiliated Hospital of Yangzhou University.

Yangzhou, Jiangsu, 225000, China

RECRUITING

MeSH Terms

Conditions

Coronary Artery Disease; Myocardial Infarction; Myocardial Ischemia

Interventions

remimazolam; Midazolam

Condition Hierarchy (Ancestors)

Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Xiaojun He, MD, Ph.D.

CONTACT

+86-13524954567; xhe34baltimore@163.com

Zhuan Zhang, MD, Ph.D.

CONTACT

+86-15062791355; zhangzhuancg@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 1. 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. 2. 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. 3. 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Model Details: 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.

Study Record Dates

• First Submitted: May 17, 2023
• First Posted: June 6, 2023
• Study Start: February 1, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 6, 2023

Record last verified: 2023-05

Locations

CN (1)