EPIC: ECG for Programming in CRT

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03936608
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arms: 2
• Actual Duration (Months): 7
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Patients with heart failure and left bundle branch block benefit from Cardiac Resynchronization Therapy (CRT) that delivers pacing from right ventricle (RV) and left ventricle (LV) synchronously, resulting in electrical ventricular resynchrony followed by revere structural cardiac remodeling and thereby reduced heart failure symptoms, hospitalizations and death. It is not known if programming an individually optimized RV-LV pacing offset to maximize electrical resynchrony can improve benefit from CRT.

The proposed study is a randomized controlled trial in patients undergoing implant of a CRT pacemaker/defibrillator device for clinical indications to evaluate benefit of RV-LV offset programming using electrocardiogram (ECG) vs. standard nominal CRT programming without RV-LV offset. Patients receiving CRT devices will be randomized to either (A) active intervention of programming RV-LV pacing offset to optimize ECG or to (B) active control of nominally programming CRT device without RV- LV offset. The patients will be followed to evaluate change in echocardiogram, quality of life, functional evaluation and a blood marker for heart failure.

Condition or Disease	Intervention/Treatment	Phase
Systolic Heart Failure; Cardiac Resynchronization Therapy; Electrocardiography	Device: Programming individualized RV-LV pacing offset to optimize ECG; Device: Nominally programming CRT device without RV-LV offset	N/A

Detailed Description

Once the eligibility for the study is determined and patient has consented for participation, all study participants will undergo a baseline evaluation (within 6 weeks prior to 2 weeks after CRT device implant/upgrade). Echocardiogram, quality-of-life questionnaire, 6-minute hall walk, blood test, vital signs, ECGs, device interrogation and baseline demographic and medical history including chart review will be obtained. After CRT device implant/upgrade, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs and echocardiography. A randomized assignment using a random allocation table in REDCap will be used to program patients to (A) intervention or (B) control RV-LV offset setting. Patients will return for study follow-up between 3-12 months. Follow-up evaluations will include echocardiography, quality-of-life questionnaire, 6-minute hall walk test, blood test, vital signs, ECGs, device interrogation, and follow-up medical history including chart review. The patients will continue to be in extended follow-up through review of their medical charts till the end of the study (12 months from date of CRT implant/upgrade of the the last study participant).

Treatment and control arms: All study patients will receive standard of care clinically indicated medical and device therapy per their treating physicians. After implant of a clinically indicated CRT device or upgrade of a preexisting pacemaker or defibrillator device to CRT system, participants will be randomized 1:1 to treatment arms (A) active intervention of programming individualized RV-LV pacing offset to optimize ECG or to (B) active control of nominally programming CRT device without RV-LV offset. Of note, both intervention and control treatment are active FDA-approved CRT therapies and no investigational device or programming will be used, and no clinically indicated treatment will be withheld from any patient. At any time, if in the judgment of the patient's treating physicians or the research team, any treatment including CRT programming different from the study protocol is necessitated for clinical reasons, the appropriate clinically indicated changes will be made. At the end of the study, if the participant is clinically doing well and the programmed CRT settings are deemed clinically appropriate they will be retained, else the CRT programming may be changed as per standard of care.

Enrolled participants who have a failed or unsatisfactory LV lead implant will not be randomized.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Electrocardiogram for Programming in Cardiac Resynchronization Therapy
• Actual Study Start Date: Apr 22, 2019
• Actual Primary Completion Date: Nov 21, 2019
• Actual Study Completion Date: Nov 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Individualized RV-LV Pacing Offset	Device: Programming individualized RV-LV pacing offset to optimize ECG; After CRT device implant, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs. The RV-LV offset that optimizes the paced QRS morphology on ECG will be programmed.
Active Comparator: No RV-LV Pacing Offset	Device: Nominally programming CRT device without RV-LV offset; After CRT device implant, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs. Nominal standard-of-care CRT programming with no RV-LV offset will be programmed.

Outcome Measures

Primary Outcome Measures

1. The Primary Outcome is Echocardiographic LV End-systolic Volume. [3-12 months]

   LV end-systolic volume is a reliable surrogate for clinical outcomes in clinical heart failure trials.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients ≥18 years of age who are able to give consent.

• Diagnosis of systolic heart failure.

• Planned to undergo new CRT device implant (or upgrade of preexisting pacemaker or defibrillator device to CRT system) for standard clinical indications.

• Expected to have over 95% heart beats resynchronized with CRT (absence of competing arrhythmias or plans to not immediately activate CRT therapy).

Exclusion Criteria:

• Unable to comply with the study follow-up.

• Life expectancy ≤1 year.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: Amit Noheria, MBBS, SM, Washington University School of Medicine
• Study Director: Sandeep Sodhi, MD, Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 13, 2019

More Information

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03936608
• Other Study ID Numbers: 201901208
• First Posted: May 3, 2019
• Last Update Posted: Dec 3, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Washington University School of Medicine: CRT Programming
• Additional relevant MeSH terms: Heart Failure, Systolic

Study Results

Participant Flow

Arm/Group Title	Individualized RV-LV Pacing Offset	No RV-LV Pacing Offset
Arm/Group Description	Programming individualized RV-LV pacing offset to optimize ECG: After CRT device implant, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs. The RV-LV offset that optimizes the paced QRS morphology on ECG will be programmed.	Nominally programming CRT device without RV-LV offset: After CRT device implant, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs. Nominal standard-of-care CRT programming with no RV-LV offset will be programmed.
Period Title: Overall Study
STARTED	2	2
COMPLETED	0	0
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Individualized RV-LV Pacing Offset	No RV-LV Pacing Offset	Total
Arm/Group Description	Programming individualized RV-LV pacing offset to optimize ECG: After CRT device implant, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs. The RV-LV offset that optimizes the paced QRS morphology on ECG will be programmed.	Nominally programming CRT device without RV-LV offset: After CRT device implant, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs. Nominal standard-of-care CRT programming with no RV-LV offset will be programmed.	Total of all reporting groups
Overall Participants	2	2	4
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	66	43	54.5
Sex: Female, Male (Count of Participants)
Female	2 100%	1 50%	3 75%
Male	0 0%	1 50%	1 25%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	2 100%	2 100%	4 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Randomization Groups (Count of Participants)
Count of Participants [Participants]	2 100%	2 100%	4 100%

Outcome Measures

1. Primary Outcome

Title	The Primary Outcome is Echocardiographic LV End-systolic Volume.
Description	LV end-systolic volume is a reliable surrogate for clinical outcomes in clinical heart failure trials.
Time Frame	3-12 months

Outcome Measure Data

Analysis Population Description

Study prematurely terminated, no data analysis was performed

Arm/Group Title	Individualized RV-LV Pacing Offset	No RV-LV Pacing Offset
Arm/Group Description	Programming individualized RV-LV pacing offset to optimize ECG: After CRT device implant, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs. The RV-LV offset that optimizes the paced QRS morphology on ECG will be programmed.	Nominally programming CRT device without RV-LV offset: After CRT device implant, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs. Nominal standard-of-care CRT programming with no RV-LV offset will be programmed.
Measure Participants	0	0

Adverse Events

Time Frame	6 months
Arm/Group Title	Individualized RV-LV Pacing Offset		No RV-LV Pacing Offset
Arm/Group Description	Programming individualized RV-LV pacing offset to optimize ECG: After CRT device implant, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs. The RV-LV offset that optimizes the paced QRS morphology on ECG will be programmed.		Nominally programming CRT device without RV-LV offset: After CRT device implant, participants will undergo physiologic evaluations at various (up to 10 or more) RV-LV offset settings including ECGs. Nominal standard-of-care CRT programming with no RV-LV offset will be programmed.
All Cause Mortality
	Individualized RV-LV Pacing Offset		No RV-LV Pacing Offset
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Serious Adverse Events
	Individualized RV-LV Pacing Offset		No RV-LV Pacing Offset
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Individualized RV-LV Pacing Offset		No RV-LV Pacing Offset
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.