LBBP + CSP Versus LBBP Alone for Cardiac Resynchronization Therapy (LOTTO-CRT)
Left Bundle Branch Pacing + Coronary Sinus Pacing Versus Left Bundle Branch Pacing Alone for Cardiac Resynchronization Therapy in Patients Eligible for CRT-P A Randomized Crossover Pilot Clinical Trial
The purpose of this pilot clinical trial is to evaluate whether a novel cardiac resynchronization strategy, called LOT-CRT, is more effective than standard physiological pacing alone (LBBAP) in patients with heart failure.
This is a randomized, single-center, crossover pilot study involving 10 patients. All participants will receive a specialized pacemaker (CRT-P) with leads implanted in two specific areas: the Left Bundle Branch Area (LBBAP) and the Coronary Sinus (CS).
Because of the crossover design, each patient will serve as their own control, receiving two different pacing configurations in a random order: Active Phase (LOT-CRT): Simultaneous pacing of the left bundle branch and the coronary sinus. Control Phase (LBBAP alone): Pacing only the left bundle branch area. Each treatment phase will last 6 months, for a total follow-up of 12 months per patient.
By testing both strategies in the same patient, this study will help clinicians identify the most effective way to restore heart synchrony and improve clinical outcomes in patients with advanced heart failure and conduction delays.
研究概览
地位
条件
详细说明
This is a single-center, randomized, crossover pilot clinical trial. Each patient will serve as their own control. Following the successful implantation of a device capable of stimulating the LBBAP and the coronary sinus, participants will be randomly assigned to one of two treatment sequences:
Sequence A: LOT-CRT (LBBAP + CS) for 6 months, followed by LBBAP alone Sequence B: LBBAP alone for 6 months, followed by LOT-CRT Each treatment phase will last 6 months, followed by an end-point evaluation and a crossover. Since the hemodynamic effect of electrical stimulation is immediate, no washout period is required between phases.
This study was designed as an exploratory pilot study; therefore, no formal sample size calculation was performed. The number of patients enrolled is considered adequate to assess the feasibility of the procedure, the safety of the crossover design, and to identify preliminary signals of clinical and electrical efficacy.
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习地点
-
-
Antioquia
-
Medellín、Antioquia、哥伦比亚、050036
- Clinica CardioVID
-
-
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Age ≥18 years
- Standard CRT-P indications according to ESC 2021 (EF ≤50%, QRS ≥130 ms, sinus rhythm or controlled AF)
- NYHA class II-IV
- Coronary venous anatomy suitable for placement of a coronary sinus electrode.
- Signed informed consent.
- Successful implantation of electrodes in the coronary sinus and in the left bundle branch area (LBBAP)
Exclusion Criteria:
- Concomitant indication for implantation of an implantable cardioverter-defibrillator (ICD) or CRT-D
- Significant uncorrected valvular disease or scheduled or anticipated cardiac surgery during the study period.
- Anatomical or technical contraindication for lead implantation in the coronary sinus or for lead implantation in the coronary sinus (such as sinus stenosis, coronary sinus branches unsuitable for cannulation, inability to advance and/or stabilize the lead, among others)
- Persistent atrial fibrillation with uncontrolled rate
- Comorbidities that may limit life expectancy to <1 year
- Participation in another clinical trial that could confound the evaluation of results within the last 6 months.
- Pregnancy or inadequate contraception
- In the researcher's opinion, the participant would not comply with the activities and visits outlined in the study protocol
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：交叉作业
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
有源比较器：Sequence A
LOT-CRT (LBBAP + CS) for 6 months, followed by LBBAP alone
|
The CS lead will be implanted in a posterolateral or lateral vein using venography and standard IV delivery sheaths. Proper lead placement is confirmed by stable fixation, pacing capture, and absence of diaphragmatic pacing. The configuration for each phase of the study (LOT-CRT or LBBAP alone) will be assigned during randomization.
其他名称：
The LBBAP lead will be implanted via a transvenous approach using the C315His sheath, targeting the left bundle branch area in the right ventricular septum, ideally between the basal septum and the mid-septal region. Criteria for confirming successful LBBAP capture will include:
其他名称：
|
|
有源比较器：Sequence B
LBBAP for 6 months only, followed by LOT-CRT
|
The CS lead will be implanted in a posterolateral or lateral vein using venography and standard IV delivery sheaths. Proper lead placement is confirmed by stable fixation, pacing capture, and absence of diaphragmatic pacing. The configuration for each phase of the study (LOT-CRT or LBBAP alone) will be assigned during randomization.
其他名称：
The LBBAP lead will be implanted via a transvenous approach using the C315His sheath, targeting the left bundle branch area in the right ventricular septum, ideally between the basal septum and the mid-septal region. Criteria for confirming successful LBBAP capture will include:
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Compare the effects of the LOT-CRT strategy versus left bundle branch block pacing (LBBAP) alone in each patient, comparing baseline to the end of the study FEVI, quality of life and functional class by NYHA.
大体时间：12 months
|
Investigators will evaluate the following parameters in each patient: Left ventricular ejection fraction (LVEF) by echocardiography and electrocardiogram; functional capacity (NYHA class) using the 6-minute walk test and symptoms reported by the patient; quality of life (MLHFQ) using the MLHFQ quality of life scale
|
12 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change in end-systolic diameter
大体时间：12 months
|
Absolute (mm) and relative (%) change in LVESV between baseline and 6 months.
|
12 months
|
|
QRS Duration
大体时间：12 months
|
Absolute (ms) and relative (%) changes in the 12-lead ECG.
|
12 months
|
|
Change in end-diastolic diameter
大体时间：12 months
|
Absolute (mm) and relative (%) change in LVEDV between baseline and 6 months.
|
12 months
|
|
NT-proBNP
大体时间：12 months
|
Absolute (ng/mL) and relative (%) change in NT-proBNP from baseline to 6 months
|
12 months
|
|
Echocardiographic responder
大体时间：12 months
|
LVEF ≥10% elevation or LVESV ≥15% decreased
|
12 months
|
|
Echocardiographic super-responder
大体时间：12 months
|
LVEF ≥50% or LVESV ≥30% decrease
|
12 months
|
|
Composite Clinical Outcome
大体时间：12 months
|
Cardiovascular Death or Hospitalization for Heart Failure
|
12 months
|
|
Procedural parameters
大体时间：12 months
|
Thresholds, P- and R-waves, impedance of each electrode.
|
12 months
|
|
Procedure Time/Fluoroscopy
大体时间：12 months
|
Total procedure time in minutes/ total fluoroscopy time in minutes.
|
12 months
|
合作者和调查者
调查人员
- 首席研究员：Juan F Agudelo, Electrophysiologist、Clinica CardioVID
- 研究主任：Susana Rios, Medical Epidemiologist、Clinica CardioVID
出版物和有用的链接
一般刊物
- Su L, Wang S, Wu S, Xu L, Huang Z, Chen X, Zheng R, Jiang L, Ellenbogen KA, Whinnett ZI, Huang W. Long-Term Safety and Feasibility of Left Bundle Branch Pacing in a Large Single-Center Study. Circ Arrhythm Electrophysiol. 2021 Feb;14(2):e009261. doi: 10.1161/CIRCEP.120.009261. Epub 2021 Jan 9.
- Herweg B, Welter-Frost A, Vijayaraman P. The evolution of cardiac resynchronization therapy and an introduction to conduction system pacing: a conceptual review. Europace. 2021 Apr 6;23(4):496-510. doi: 10.1093/europace/euaa264.
- Chung MK, Patton KK, Lau CP, Dal Forno ARJ, Al-Khatib SM, Arora V, Birgersdotter-Green UM, Cha YM, Chung EH, Cronin EM, Curtis AB, Cygankiewicz I, Dandamudi G, Dubin AM, Ensch DP, Glotzer TV, Gold MR, Goldberger ZD, Gopinathannair R, Gorodeski EZ, Gutierrez A, Guzman JC, Huang W, Imrey PB, Indik JH, Karim S, Karpawich PP, Khaykin Y, Kiehl EL, Kron J, Kutyifa V, Link MS, Marine JE, Mullens W, Park SJ, Parkash R, Patete MF, Pathak RK, Perona CA, Rickard J, Schoenfeld MH, Seow SC, Shen WK, Shoda M, Singh JP, Slotwiner DJ, Sridhar ARM, Srivatsa UN, Stecker EC, Tanawuttiwat T, Tang WHW, Tapias CA, Tracy CM, Upadhyay GA, Varma N, Vernooy K, Vijayaraman P, Worsnick SA, Zareba W, Zeitler EP. 2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure. Heart Rhythm. 2023 Sep;20(9):e17-e91. doi: 10.1016/j.hrthm.2023.03.1538. Epub 2023 May 20.
- Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IM, Barrabes JA, Boriani G, Braunschweig F, Brignole M, Burri H, Coats AJS, Deharo JC, Delgado V, Diller GP, Israel CW, Keren A, Knops RE, Kotecha D, Leclercq C, Merkely B, Starck C, Thylen I, Tolosana JM; ESC Scientific Document Group. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J. 2021 Sep 14;42(35):3427-3520. doi: 10.1093/eurheartj/ehab364. No abstract available.
- Sieniewicz BJ, Gould J, Porter B, Sidhu BS, Teall T, Webb J, Carr-White G, Rinaldi CA. Understanding non-response to cardiac resynchronisation therapy: common problems and potential solutions. Heart Fail Rev. 2019 Jan;24(1):41-54. doi: 10.1007/s10741-018-9734-8.
- Burri H, Jastrzebski M, Cano O, Curila K, de Pooter J, Huang W, Israel C, Joza J, Romero J, Vernooy K, Vijayaraman P, Whinnett Z, Zanon F. EHRA clinical consensus statement on conduction system pacing implantation: endorsed by the Asia Pacific Heart Rhythm Society (APHRS), Canadian Heart Rhythm Society (CHRS), and Latin American Heart Rhythm Society (LAHRS). Europace. 2023 Apr 15;25(4):1208-1236. doi: 10.1093/europace/euad043.
- Upadhyay GA, Jastrzebski M, Foley P, Chandrasekaran B, Whinnett Z, Schaller RD, Gardas R, Richardson T, Moskal P, Kudlik D, Stadler RW, Zimmerman P, Burrell J, Waxman R, Cornelussen RN, Lyne J, Herweg B, Vijayaraman P. Echocardiographic response from left bundle branch area pacing optimized cardiac resynchronization therapy (LOT-CRT) vs traditional CRT. Heart Rhythm. 2025 Oct;22(10):2616-2624. doi: 10.1016/j.hrthm.2025.04.026. Epub 2025 Apr 18.
- Chen X, Li X, Bai Y, Wang J, Qin S, Bai J, Wang W, Liang Y, Chen H, Su Y, Ge J. Electrical Resynchronization and Clinical Outcomes During Long-Term Follow-Up in Intraventricular Conduction Delay Patients Applied Left Bundle Branch Pacing-Optimized Cardiac Resynchronization Therapy. Circ Arrhythm Electrophysiol. 2023 Sep;16(9):e011761. doi: 10.1161/CIRCEP.122.011761. Epub 2023 Aug 14.
- Parale C, Bootla D, Jain A, Satheesh S, Anantharaj A, Ahmed AS, Sukumaran SK, Balaguru S, Selvaraj R. Comparison of electrocardiographic parameters between left bundle optimized cardiac resynchronization therapy (LOT-CRT) and left bundle branch pacing-cardiac resynchronization therapy (LBBP-CRT). Pacing Clin Electrophysiol. 2023 Aug;46(8):840-847. doi: 10.1111/pace.14793. Epub 2023 Jul 21.
- Jastrzebski M, Foley P, Chandrasekaran B, Whinnett Z, Vijayaraman P, Upadhyay GA, Schaller RD, Gardas R, Richardson T, Kudlik D, Stadler RW, Zimmerman P, Burrell J, Waxman R, Cornelussen RN, Lyne J, Herweg B. Multicenter Hemodynamic Assessment of the LOT-CRT Strategy: When Does Combining Left Bundle Branch Pacing and Coronary Venous Pacing Enhance Resynchronization?: Primary Results of the CSPOT Study. Circ Arrhythm Electrophysiol. 2024 Nov;17(11):e013059. doi: 10.1161/CIRCEP.124.013059. Epub 2024 Oct 23.
- Vijayaraman P. Left Bundle Branch Pacing Optimized Cardiac Resynchronization Therapy: A Novel Approach. JACC Clin Electrophysiol. 2021 Aug;7(8):1076-1078. doi: 10.1016/j.jacep.2021.04.005. Epub 2021 Jul 28. No abstract available.
- Glikson M, Burri H, Abdin A, Cano O, Curila K, De Pooter J, Diaz JC, Drossart I, Huang W, Israel CW, Jastrzebski M, Joza J, Karvonen J, Keene D, Leclercq C, Mullens W, Pujol-Lopez M, Rao A, Vernooy K, Vijayaraman P, Zanon F, Michowitz Y, Nielsen JC, Boersma L, Blomstrom-Lundqvist C, Kronborg MB, Chung MK, Tse HF, Khan HR, Leyva F, Rojel-Martinez U, Rucinski M, Varma N. European Society of Cardiology (ESC) clinical consensus statement on indications for conduction system pacing, with special contribution of the European Heart Rhythm Association of the ESC and endorsed by the Asia Pacific Heart Rhythm Society, the Canadian Heart Rhythm Society, the Heart Rhythm Society, and the Latin American Heart Rhythm Society. Europace. 2025 Mar 28;27(4):euaf050. doi: 10.1093/europace/euaf050.
- Jastrzebski M, Moskal P, Huybrechts W, Curila K, Sreekumar P, Rademakers LM, Ponnusamy SS, Herweg B, Sharma PS, Bednarek A, Rajzer M, Vijayaraman P. Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT): Results from an international LBBAP collaborative study group. Heart Rhythm. 2022 Jan;19(1):13-21. doi: 10.1016/j.hrthm.2021.07.057. Epub 2021 Jul 30.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他研究编号
- Clinica CardioVID
- ERP -2025-14209 (其他赠款/资助编号：Medtronic)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
IPD 计划说明
Individual participant data, appropriately anonymized, that support the reported results will be made available to qualified researchers for the purposes of scientific research or meta-analysis. Requests must be addressed to the Principal Investigator and include a formal proposal. All requests will be subject to approval by the institutional ethics committee. As this is a study with a small sample size (10 patients), the protocol strictly enforces confidentiality; therefore, prior approval is always required to share these data.
The data will be available from 6 months to 5 years following the publication of the main results.
IPD 共享时间框架
IPD 共享访问标准
IPD 共享支持信息类型
- 研究方案
- 树液
- 企业社会责任
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
在美国制造并从美国出口的产品
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.