Partial Cardiac Denervation for Preventing Atrial Fibrillation After CABG (CALM)
Cardiac Autonomic Neuromodulation in Myocardial Revascularization (CALM): A Multicenter Randomized Controlled Trial of Partial Cardiac Denervation for the Prevention of Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting
Postoperative atrial fibrillation (POAF) is the most common arrhythmia following cardiac surgery and is associated with increased risks of mortality, stroke, myocardial infarction, and hospital readmission. The cardiac autonomic nervous system plays an important role in the development of POAF and may represent a potential target for preventive intervention.
The CALM trial is a multicenter, randomized controlled trial designed to evaluate the efficacy and safety of partial cardiac denervation for the prevention of POAF in patients undergoing isolated coronary artery bypass grafting (CABG). A total of approximately 1,470 participants will be randomly assigned in a 1:1 ratio to undergo CABG with partial cardiac denervation or CABG alone. Partial cardiac denervation consists of transection of the ligament of Marshall and resection of the Waterston fat pad.
The trial will evaluate the incidence of POAF within the first 6 postoperative days and the occurrence of long-term adverse clinical events. Participants will undergo scheduled rhythm monitoring and clinical follow-up, and all participants will be followed until the last enrolled participant completes 3 years of follow-up after surgery.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
Postoperative atrial fibrillation (POAF) is a common complication after coronary artery bypass grafting (CABG) and is associated with increased risks of stroke, myocardial infarction, prolonged hospitalization, and other adverse outcomes. Autonomic imbalance and excessive activation of the intrinsic cardiac autonomic nervous system are considered important contributors to the development of POAF. Previous studies of pharmacological or biological autonomic modulation have shown variable efficacy, and their effects may be transient.
A previous single-center randomized trial conducted by the investigators showed that partial cardiac denervation, consisting of transection of the ligament of Marshall and resection of the Waterston fat pad, reduced the incidence of POAF after CABG without increasing perioperative complications. The CALM trial is designed to evaluate whether these findings can be reproduced across multiple centers and to investigate the potential long-term clinical and autonomic effects of this intervention.
This is a prospective, multicenter, randomized controlled trial involving approximately 1,470 patients undergoing isolated CABG with or without cardiopulmonary bypass. Participants will be randomly assigned in a 1:1 ratio to partial cardiac denervation in addition to standard CABG or to standard CABG alone. Centralized randomization will be stratified by participating center and baseline CHA2DS2-VASc score. Treatment allocation will be disclosed to the operating surgeon only after induction of anesthesia. Participants, outcome assessors, electrocardiographic reviewers, clinical event adjudicators, and statisticians will remain blinded to treatment allocation.
In the intervention group, the ligament of Marshall, located between the left atrial appendage and the left pulmonary veins, will be transected using electrocautery. The Waterston fat pad, located in the interatrial groove between the right atrium and the right pulmonary veins, will then be completely resected down to the epicardial surface. No additional denervation procedure will be performed in the control group. Other aspects of CABG and perioperative care will follow routine clinical practice at each participating center.
Continuous electrocardiographic monitoring will be performed during the early postoperative period, and scheduled ambulatory electrocardiographic monitoring will be conducted during follow-up. Electrocardiographic recordings will be centrally reviewed by an independent ECG Core Laboratory. Suspected clinical endpoint events will be adjudicated by an independent Clinical Event Adjudication Committee blinded to treatment allocation. Participants will undergo scheduled clinical follow-up for assessment of arrhythmias, cardiac autonomic function, and long-term clinical outcomes. All participants will be followed until the last enrolled participant has completed 3 years of follow-up after surgery.
研究の種類
研究の種類
入学 (推定)
入学
段階
段階
- 適用できない
連絡先と場所
研究連絡先
研究連絡先
- 名前:Ziang Yang, M.D.
- 電話番号:86+19801109287
- メール:yzang47@163.com
研究場所
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Beijing Municipality
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Beijing、Beijing Municipality、中国、100000
- Fuwai Hospital, PUMC & CAMS
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コンタクト:
- Wei Feng, M.D.
- 電話番号:86+13801018685
- メール:fengwei@fuwai.com
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主任研究者:
- Wei Feng, M.D.
-
主任研究者:
- Zhan Hu, M.D.
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Guangdong
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Guangzhou、Guangdong、中国、510080
- Guangdong Provincial People's Hospital
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コンタクト:
- Qiang Gao, M.D.
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Henan
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Zhenzhou、Henan、中国、451464
- Fuwai Central China Cardiovascular Hospital
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コンタクト:
- Junlong Hu, M.D.
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Hunan
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Changsha、Hunan、中国、410011
- The Second Xiangya Hospital of Central South University
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コンタクト:
- Xiaobo Liao, M.D.
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Jiangsu
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Nanjing、Jiangsu、中国、210006
- Nanjing First Hospital, Nanjing Medical University
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コンタクト:
- Fei Xiang, M.D.
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-
参加基準
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Adults aged 18 years or older.
- Scheduled to undergo isolated coronary artery bypass grafting, either with or without cardiopulmonary bypass.
- Able and willing to provide written informed consent.
- No atrial fibrillation detected on preoperative 24-hour electrocardiographic monitoring.
Exclusion Criteria:
- Previous cardiac surgery.
- Emergency surgery.
- Preoperative critical condition.
- Left ventricular ejection fraction of 30% or lower.
- Left atrial diameter greater than 50 mm.
- Prior history of atrial fibrillation.
- Use of antiarrhythmic medications other than beta-blockers within 2 weeks before surgery.
- Planned concomitant cardiac procedures, including but not limited to congenital heart disease surgery or left ventricular reconstruction.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:防止
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:トリプル
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
介入なし:Control group
CABG alone |
|
|
実験的:Intervention group
Partial cardiac denervation + CABG. Partial cardiac denervation consists of transection of the ligament of Marshall and resection of the Waterston fat pad. |
The intervention has been described in previous studies. Briefly, intraoperative partial cardiac denervation is achieved by transection of the left LOM and resection of the right Waterston fat pad using electrocautery. During the procedure, the pulmonary trunk is first gently retracted to the right to expose the LOM located between the left atrial appendage and the left pulmonary veins. The LOM is then transected using electrocautery. Subsequently, the right atrium is retracted to the left to expose the Waterston fat pad located in the interatrial groove. The Waterston fat pad is completely excised with electrocautery down to the epicardial surface. |
この研究は何を測定していますか?
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of Postoperative Atrial Fibrillation Within 6 Postoperative Days
時間枠:From admission to the intensive care unit after surgery until postoperative day 6.
|
The proportion of participants with documented new-onset postoperative atrial fibrillation (POAF). POAF is defined as an episode of atrial fibrillation characterized by irregularly irregular RR intervals and the absence of discernible P waves, lasting more than 30 seconds. Continuous electrocardiographic recordings will be centrally reviewed by the blinded ECG Core Laboratory. |
From admission to the intensive care unit after surgery until postoperative day 6.
|
|
Time to First Occurrence of the Composite Clinical Outcome
時間枠:From surgery until 3 years after enrollment of the last participant, with a minimum follow-up of 3 years for each participant.
|
Time from surgery to the first occurrence of any component of the composite outcome, including all-cause death, stroke, systemic embolism, myocardial infarction, readmission for cardiac reasons, or post-discharge atrial fibrillation. Suspected clinical events will be adjudicated by an independent Clinical Event Adjudication Committee blinded to treatment allocation. Post-discharge atrial fibrillation events will be reviewed by the blinded ECG Core Laboratory. |
From surgery until 3 years after enrollment of the last participant, with a minimum follow-up of 3 years for each participant.
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Postoperative Length of Hospital Stay
時間枠:From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days)
|
The number of days from the date of surgery to hospital discharge. |
From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days)
|
|
Total Hospitalization Costs
時間枠:From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days)
|
Total medical costs incurred during the index hospitalization. |
From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days)
|
|
Incidence of Perioperative All-Cause Mortality
時間枠:From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days)
|
The proportion of participants who die from any cause during the perioperative hospitalization. |
From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days)
|
|
Incidence of Perioperative New-Onset Stroke
時間枠:From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days)
|
The proportion of participants who experience a new-onset stroke during the perioperative hospitalization, as adjudicated by the blinded Clinical Event Adjudication Committee according to predefined endpoint criteria. |
From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days)
|
|
Incidence of Perioperative Myocardial Infarction
時間枠:From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days)
|
The proportion of participants who experience myocardial infarction during the perioperative hospitalization, as adjudicated by the blinded Clinical Event Adjudication Committee according to predefined endpoint criteria. |
From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days)
|
|
Postoperative Atrial Fibrillation Burden Within 6 Postoperative Days
時間枠:From admission to the intensive care unit after surgery until postoperative day 6.
|
The proportion of analyzable electrocardiographic monitoring time spent in atrial fibrillation during the early postoperative monitoring period, as determined by the blinded ECG Core Laboratory. |
From admission to the intensive care unit after surgery until postoperative day 6.
|
|
Number of Postoperative Atrial Fibrillation Episodes Within 6 Postoperative Days
時間枠:From admission to the intensive care unit after surgery until postoperative day 6.
|
The total number of documented postoperative atrial fibrillation episodes per participant during the early postoperative monitoring period, as determined by the blinded ECG Core Laboratory. |
From admission to the intensive care unit after surgery until postoperative day 6.
|
|
Duration of Postoperative Atrial Fibrillation Within 6 Postoperative Days
時間枠:From admission to the intensive care unit after surgery until postoperative day 6.
|
The cumulative duration of documented postoperative atrial fibrillation episodes during the early postoperative monitoring period, as determined by the blinded ECG Core Laboratory. |
From admission to the intensive care unit after surgery until postoperative day 6.
|
|
Incidence of Post-Discharge Atrial Fibrillation
時間枠:From discharge until the end of study follow-up, with a minimum follow-up of 3 years for each participant.
|
The proportion of participants with atrial fibrillation documented after discharge by scheduled 3-day ambulatory electrocardiographic monitoring or by clinically obtained electrocardiographic recordings. All suspected events will be reviewed by the blinded ECG Core Laboratory. |
From discharge until the end of study follow-up, with a minimum follow-up of 3 years for each participant.
|
|
Post-Discharge Atrial Fibrillation Burden
時間枠:At 3 months, 1 year, and annually thereafter until study completion, with a minimum follow-up of 3 years for each participant.
|
The proportion of analyzable ambulatory electrocardiographic monitoring time spent in atrial fibrillation during each scheduled 3-day monitoring period, as determined by the blinded ECG Core Laboratory. |
At 3 months, 1 year, and annually thereafter until study completion, with a minimum follow-up of 3 years for each participant.
|
|
Incidence of Non-Atrial Fibrillation Arrhythmias
時間枠:From surgery until the end of study follow-up, with a minimum follow-up of 3 years for each participant.
|
The proportion of participants with predefined non-atrial fibrillation arrhythmias, including third-degree atrioventricular block, frequent premature atrial contractions, and frequent premature ventricular contractions, as determined by the blinded ECG Core Laboratory. |
From surgery until the end of study follow-up, with a minimum follow-up of 3 years for each participant.
|
|
Heart Rate Variability Parameters
時間枠:During the first 6 postoperative days and at 3 months, 1 year, and annually thereafter until study completion, with a minimum follow-up of 3 years for each participant.
|
Cardiac autonomic function will be assessed using time-domain and frequency-domain heart rate variability parameters obtained from electrocardiographic monitoring. Measurements will be centrally analyzed by the blinded ECG Core Laboratory. |
During the first 6 postoperative days and at 3 months, 1 year, and annually thereafter until study completion, with a minimum follow-up of 3 years for each participant.
|
|
Health-Related Quality of Life Assessed Using the EuroQol 5-Dimension 5-Level Questionnaire
時間枠:At 3 months, 1 year, and annually thereafter until study completion, with a minimum follow-up of 3 years for each participant.
|
Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L). An EQ-5D-5L health utility index will be calculated using the Chinese population value set. The index ranges from -0.391 to 1.000, with higher scores indicating better health status. A score of 1.000 represents full health, 0 represents a health state equivalent to death, and negative values represent health states considered worse than death. Scores will be compared between the two treatment groups at scheduled follow-up assessments. |
At 3 months, 1 year, and annually thereafter until study completion, with a minimum follow-up of 3 years for each participant.
|
|
Atrial Fibrillation-Related Quality of Life Assessed Using the Atrial Fibrillation Effect on QualiTy-of-Life Questionnaire
時間枠:At 3 months, 1 year, and annually thereafter until study completion, with a minimum follow-up of 3 years for each participant.
|
Atrial fibrillation-related quality of life will be assessed using the Atrial Fibrillation Effect on QualiTy-of-Life Questionnaire (AFEQT). The AFEQT Overall Summary Score ranges from 0 to 100, with higher scores indicating better atrial fibrillation-related health status and quality of life and lower scores indicating greater impairment. Scores will be compared between the two treatment groups at scheduled follow-up assessments. |
At 3 months, 1 year, and annually thereafter until study completion, with a minimum follow-up of 3 years for each participant.
|
|
Incidence of Reoperation for Bleeding
時間枠:From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days).
|
The proportion of participants who require surgical re-exploration because of postoperative bleeding. |
From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days).
|
|
Incidence of Postoperative Blood Transfusion
時間枠:From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days).
|
The proportion of participants who receive a blood transfusion after surgery during the index hospitalization. |
From the date of surgery through discharge from the index hospitalization (an estimated period of up to 30 days).
|
|
Incidence of Delayed Moderate or Greater Pericardial Effusion
時間枠:From discharge from the index hospitalization through 30 days after discharge.
|
The proportion of participants who develop new-onset moderate or greater pericardial effusion within 30 days after discharge from the index hospitalization, as documented by echocardiography. |
From discharge from the index hospitalization through 30 days after discharge.
|
協力者と研究者
協力者
協力者
捜査官
捜査官
- 主任研究者:Mario Gaudino, M.D.、Weill Medical College of Cornell University
研究記録日
主要日程の研究
研究開始 (推定)
研究開始
一次修了 (推定)
一次修了
研究の完了 (推定)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
その他の研究ID番号
- NCRC2026001
- 2026-12M-SXZX1-05 (その他の助成金/資金番号:Chinese Academy of Medical Sciences)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- CSR
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