Guided CRT Implantation for Chronic Heart Failure

(CRT-DRIVE Trial)

Recruiting at 18 trial locations

Overseen By Claudia M Amatruda, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: XSpline S.p.A.

Disqualifiers: Atrial fibrillation, Pacemaker, Angina, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for implanting a device to assist individuals with chronic heart failure. It employs innovative technology to customize device placement using 3D images of the heart's electrical activity and veins. The researchers hope this approach will significantly improve heart function after six months. Suitable candidates have heart failure with symptoms such as shortness of breath, have received stable treatment for six months, and meet specific heart condition criteria, such as left bundle branch block (a particular heart rhythm issue). As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could transform heart failure treatment.

Will I have to stop taking my current medications?

The trial requires that participants have been on stable medical treatment for at least 6 months, so you will not need to stop your current medications if they have been stable.

What prior data suggests that this CRT implantation method is safe?

Research has shown that cardiac resynchronization therapy (CRT), a treatment for heart failure, is generally safe. Studies have found that most patients, including older adults, tolerate CRT well, so age should not be a barrier to receiving it. Although trials for the new XSpline-guided CRT are recent, CRT itself has been safely used in many people.

Most patients experience few serious side effects with CRT. However, like any medical procedure, some risks exist. Discussing these risks with a doctor is important for better understanding. Overall, evidence suggests that CRT, including this new guided method, is a safe option for treating heart failure. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Guided CRT Implantation for Chronic Heart Failure trial because it aims to demonstrate that using the XSpline guidance system can be just as effective as current CRT methods. Unlike the standard CRT procedures, which rely on anatomical landmarks and fluoroscopy, XSpline offers a more precise and potentially safer way to guide the implantation of CRT devices. This could lead to improved outcomes for patients, with the hope of achieving a similar or better reduction in heart failure symptoms as existing treatments. If successful, this method could make CRT implantation more accessible and effective for a broader range of patients.

What evidence suggests that this CRT implantation guided by XSpline is effective for chronic heart failure?

Research has shown that Cardiac Resynchronization Therapy (CRT), when guided by XSpline technology, may improve heart function in people with chronic heart failure. In earlier studies, about 75% of patients receiving CRT experienced significant improvement, with a 15% or more reduction in the size of their heart's left ventricle after six months. This trial will use the XSpline method to guide CRT implantation, employing advanced 3D images to accurately place the device leads in the heart. This approach may enhance the treatment's precision and effectiveness by targeting the areas of the heart that need the most help, potentially improving patient outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Angelo Auricchio, MD PhD FESC

Principal Investigator

Istituto Cardiocentro Ticino

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic heart failure, left bundle branch block (LBBB), and a specific type of heart rhythm issue. They must have symptoms of heart failure despite stable treatment for 6 months and not be pregnant or at risk of pregnancy without contraception. Exclusions include recent heart attacks, certain surgeries, severe kidney disease, other major cardiac conditions, or participation in conflicting studies.

Inclusion Criteria

My medical treatment has been stable for at least 6 months.

I have heart failure symptoms that affect my daily activities.

I haven't had any heart procedures in the last 6 months.

Exclusion Criteria

I had a heart attack in the last 40 days.

I have unstable chest pain.

Subject has a life expectancy of less than one year in the opinion of the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-procedural Planning

Creation of a cloud-based pre-procedural multimodality CRT-roadmap by integration of 3D images from ECG and coronary venous anatomy from cardiac computed tomography

1-2 weeks

CRT Implantation

CRT implantation guided by non-invasive electrical and venous anatomy assessment using XSPLINE technology

1 week

Follow-up

Participants are monitored for safety and effectiveness after CRT implantation, with a focus on reduction of left ventricular end-systolic volume

6 months

What Are the Treatments Tested in This Trial?

Interventions

• XSpline

Trial Overview

The study tests if guiding CRT implantation using XSpline—a non-invasive method combining ECG and CT imaging to create a detailed roadmap—improves outcomes. The goal is that patients will show significant improvement in the size of their left ventricle after six months compared to standard placement methods.

How Is the Trial Designed?

Group I: CRT implantation guided by XSpline Experimental Treatment 1 Intervention

The sample size estimation was based on two recent studies including CRT patients with similar clinical and demographic characteristics as in this study: the SMART-MSP and the SMART CRT. The SMART-MSP is a prospective, observational study that enrolled 584 CRT recipients at 52 US sites. In a typical modern CRT population, 75% of patients had a reduction of the end-systolic volume ≥ 15% at 6-month follow-up. The SMART-CRT study enrolled 699 CRT patients randomized to a treatment arm and a control group. At 6-months follow-up, a reduction of LVESV ≥15% was achieved for 67.7% of the patients in the control group and for 74.8% of those in the treatment arm. Therefore, it is assumed that in a modern CRT population at least 70% of the patients will have a reduction of the LVESV ≥15% of the baseline value at 6-months after CRT implantation. To demonstrate that this proportion of patients can be equally achieved with the approach tested in this study at least 150 patients need to be included.

XSpline is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as CRT for:

• Heart failure
• Left bundle branch block
• Irregular heart signaling conditions

Approved in United States as CRT for:

• Moderate to severe heart failure
• Left bundle branch block
• Irregular heart signaling conditions

Approved in Canada as CRT for:

• Heart failure
• Left bundle branch block
• Irregular heart signaling conditions

Approved in Japan as CRT for:

• Heart failure
• Left bundle branch block
• Irregular heart signaling conditions

Approved in China as CRT for:

• Heart failure
• Left bundle branch block
• Irregular heart signaling conditions

Approved in Switzerland as CRT for:

• Heart failure
• Left bundle branch block
• Irregular heart signaling conditions

Who Is Running the Clinical Trial?

XSpline S.p.A.

Lead Sponsor

Trials

1

Recruited

150+

Published Research Related to This Trial

The combination of electromagnetic navigation and electroanatomical mapping systems significantly reduces x-ray exposure during the implantation of cardiac resynchronization therapy (CRT) devices.

This technique allows for more precise targeting of delayed activation regions in the heart, which can enhance the effectiveness of CRT by avoiding scar tissue and improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining electromagnetic navigation and 3-D mapping to reduce fluoroscopy time and achieve optimal CRT response. Barbero, U., Budano, C., Golzio, PG., et al.[2019]

In a study of 151 patients who received complex cardiac devices (ICD, CRT-P, CRT-D) over two years, the overall procedural success rate was an impressive 99.3%, indicating high efficacy in implantation.

Complications occurred in 9.3% of cases, with lead displacement being the most common issue (5.3%), but there were no procedure-related deaths, highlighting the safety of these procedures when performed by experienced clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complex cardiac pacing in the setting of a district general hospital: procedural success and complications. Rahbi, H., El-Din, M., Salloum, M., et al.[2020]

The use of cardiac resynchronization therapy (CRT) devices, including CRT-P and CRT-D, has significantly increased due to better operator experience and expanded patient eligibility.

In a specific case, innovative device programming successfully achieved effective biventricular pacing despite challenges with repeated dislodgement of the atrial lead, highlighting advancements in CRT technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a novel pacing mode to achieve biventricular pacing in a patient with recurrent atrial lead dislodgement after CRT-D implantation. Devidutta, S., Sridevi, C., Narasimhan, C.[2020]

The study demonstrates the successful use of an electroanatomic navigation system (EnSite NavX) for the implantation of a biventricular implantable cardioverter-defibrillator (CRT-ICD) in four patients with dilated cardiomyopathy, highlighting its feasibility and safety.

Using this navigation system significantly reduced X-ray exposure during the procedure and improved the accuracy of lead placement in the coronary sinus, suggesting it could enhance patient safety and procedural outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implantation of a biventricular implantable cardioverter-defibrillator guided by an electroanatomic mapping system. Del Greco, M., Marini, M., Bonmassari, R.[2021]

A 76-year-old male with severe heart failure received a CRT pacemaker (CRT-P) after careful evaluation, but he experienced sudden cardiac death two months later, highlighting the risks even in low-risk patients.

The case emphasizes the need for more clinical trial data to guide clinicians in choosing between CRT-P and CRT-D devices, as sudden cardiac death can occur despite the absence of prior symptoms or device malfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sudden cardiac death after implantation of a cardiac resynchronization therapy pacemaker: a case report illustrating that not always less is more. Vollmann, D., Hansen, C., Hunold, P., et al.[2022]

In a study of 84 heart failure patients with biventricular pacemakers (CRT-P), 13.1% experienced unsustained ventricular tachyarrhythmias during an average follow-up of 29 months, indicating that while CRT-P can be tolerated, there is still a risk of arrhythmias.

The upgrade to a CRT-D (with a defibrillator) did not significantly prevent sudden death, as evidenced by one patient who died suddenly 15 months after the upgrade, suggesting that CRT-P may be a viable option for certain patients without an ICD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of ventricular arrhythmias in patients with cardiac resynchronization therapy without back-up ICD: a single-center experience. Bortnik, M., Degiovanni, A., Dell'era, G., et al.[2014]

In a study of 542 patients with congestive heart failure, those with a cardiac resynchronization therapy-defibrillator (CRT-D) had significantly lower all-cause mortality (18.5%) compared to those with a cardiac resynchronization therapy-pacemaker (CRT-P) (38.8%), suggesting CRT-D offers better survival benefits.

Patients with chronic renal failure, diabetes mellitus, and a history of atrial fibrillation were identified as having a higher risk of death, while treatment with beta-blockers and CRT-D devices were associated with lower mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mortality of heart failure patients after cardiac resynchronization therapy: identification of predictors. Bai, R., Di Biase, L., Elayi, C., et al.[2009]

In a study of 60 patients with chronic heart failure, those who received implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator (ICD/CRT-D) showed a significantly lower readmission rate for heart failure (30.0%) compared to the control group (56.67%), indicating improved management of heart failure with remote monitoring.

The ICD/CRT-D group also experienced a much faster diagnosis time for ventricular tachycardia/ventricular events (2.55 days) compared to the control group (37.32 days), allowing for quicker medical intervention and potentially better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ICD/CRT-D Implantation on Adverse Events and Readmission Rate in Patients with Chronic Heart Failure (CHF). Liu, P., Xing, L.[2023]

In a study of 360 heart failure patients with significant right ventricular pacing, upgrading to cardiac resynchronization therapy with defibrillator (CRT-D) significantly reduced the risk of all-cause mortality and heart failure hospitalization compared to standard ICD therapy, with only 32.4% experiencing adverse outcomes in the CRT-D group versus 78.9% in the ICD group.

The safety profile was similar between CRT-D and ICD groups, with comparable rates of procedure-related complications, indicating that CRT-D is a safer and more effective option for patients with heart failure and high right ventricular pacing burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upgrade of right ventricular pacing to cardiac resynchronization therapy in heart failure: a randomized trial. Merkely, B., Hatala, R., Wranicz, JK., et al.[2023]

From 2003 to 2013, approximately 439,010 cardiac resynchronization therapy (CRT) devices were implanted in the U.S., with a complication rate of 6.1%, indicating that while CRT is generally safe, some patients do experience complications.

The study found that the severity of comorbid conditions among patients increased over the years, leading to a higher rate of complications during CRT procedures, particularly in older patients and females, although in-hospital mortality and length of stay did not show significant changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization and in-hospital complications of cardiac resynchronization therapy: trends in the United States from 2003 to 2013. Hosseini, SM., Moazzami, K., Rozen, G., et al.[2019]

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