Response of Cardiac Resynchronization Therapy Optimization With Ventricle to Ventricle Timing in Heart Failure Patients

• Sponsor: Abbott Medical Devices (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00187200
• Collaborator: (none)
• Enrollment: 816
• Location: 1
• Arms: 2
• Duration (Months): 62.9
• Patients Per Site Per Month: 13

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the benefit of interventricular (V-V) delay optimization in reducing the non-responder rate in patients with cardiac resynchronization defibrillator (CRT-D) devices. The primary endpoint of this study is CRT responder rate.

For patients enrolled with new CRT-D systems, patients are considered non-responders if BOTH of the following requirements are fulfilled:

• < 10% improvement in 6-minute hall walk, and

• no class improvement or worsening in New York Heart Association (NYHA) scale.

For those receiving CRT-D devices as replacements of older CRT-D systems, patients are considered non-responders if BOTH of the following requirements are fulfilled:

• 1 heart failure (HF) related hospitalization, and

• no class improvement or worsening in NYHA scale.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Device: Simultaneous VV Pacing; Device: Sequential VV Pacing	Phase 4

Detailed Description

Study Methods

• This is a prospective, randomized (simultaneous biventricular (BiV) pacing vs. sequential BiV pacing) study.

• Any patient that receives an FDA approved St. Jude Medical (SJM) CRT-D with V-V timing is eligible for enrollment.

• At 3 months post enrollment (or at implant for CRT-D replacements), patients screened as non-responders are randomized to either simultaneous or sequential BiV pacing. Patients requiring a replacement CRT-D device that are identified as non-responders to CRT are enrolled at the screening/randomization visit.

• Patients are followed for a period of 6 months post randomization:

• Enrollment (1 week pre CRT-D implant to < 2 weeks post CRT-D implant)

• Screening/Randomization Visit (3 months post enrollment)

• Follow-up Visit (6 months post randomization)

• Total # of centers - 80 centers

• Sample size - 800 patients screened for CRT non-responders

Study Design

• Study Type: Interventional
• Actual Enrollment: 816 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: RESPONSE HF - Response of Cardiac Resynchronization Therapy Optimization With Interventricular (VV) Timing in Heart Failure Patients
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Simultaneous VV Pacing Programmed to simultaneous biventricular pacing	Device: Simultaneous VV Pacing; Right ventricular and left ventricular pacing delivered simultaneously.
Active Comparator: Sequential VV Pacing Programmed to sequential biventricular pacing	Device: Sequential VV Pacing; Right ventricular and left ventricular pacing delivered sequentially.

Outcome Measures

Primary Outcome Measures

1. CRT Responder Rate [6 months]

   Patients underwent baseline NYHA class and 6-minute hall walk distance (6-MHWD) assessment. After device implantation AV delays were optimized and all patients were programmed to simultaneous biventricular (BiV) pacing. At the 3-month follow-up, the NYHA class and 6-MHWD were reassessed. Non-responders were randomized 1:1 to either sequential BiV pacing with VV optimization or simultaneous BiV pacing. The responder rate at 6 months post randomization was compared between the two groups. Which is why the numbers are broken further down in the Outcome Measure table.

Secondary Outcome Measures

1. NYHA Class Progression [6 months]

   New York Heart Association (NYHA) functional classification provides a way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina pain.

2. 6 Minute Hall Walk Distance Test (6-MHWD) [6 months]

   Patients were considered non-responders if the 6-MHWD had not improved by greater than or equal to 10% compared to baseline. This statement is accurate and appropriate.

3. Left Ventricular Ejection Fraction (LVEF) [Randomization and 9 months]

   Ejection fraction is a measurement of the percentage of blood leaving your heart each time it contracts. The left ventricle is the heart's main pumping chamber, so ejection fraction is usually measured only in the left ventricle (LV).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient has a standard indication for a CRT-D.

• Patient has the ability to complete a 6-minute hall walk with the only limiting factor to be fatigue or shortness of breath.

• Patient is geographically stable and willing to comply with the required follow-up schedule.

• Prior to 1 month of randomization, patient's HF medications are maintained stable and remain stable throughout the study.

• Patients requiring a CRT-D replacement must comply with BOTH of the following:

• 1 HF related hospitalization

• No class improvement or worsening in NYHA scale

Exclusion Criteria:

• Patient's life expectancy is less than 12 months.

• Patient has had cardiac surgery within 6 months of enrollment.

• Patient has an epicardial ventricular lead system.

• Patient is less than 18 years old.

• Patient is pregnant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ohio State University	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Abbott Medical Devices

Investigators

• Principal Investigator: Raul Weiss, MD, Ohio State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abbott Medical Devices
• ClinicalTrials.gov Identifier: NCT00187200
• Other Study ID Numbers: CRD299
• First Posted: Sep 16, 2005
• Last Update Posted: Feb 5, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Recruitment Details	816 patients were enrolled in the trial. Of the patients screened at the 3-month follow up, 572 patients were classified as responders and 102 patients as non-responders.
Pre-assignment Detail	102 of the patients were non-responders, but only 93 were randomized of which 57 completed the study and had data available for analysis. of the 816 participants screened only 93 wre randomized to treatment. This statement is accurate and appropriate.

Arm/Group Title	Simultaneous Pacing V-V Timing	Sequential VV Pacing
Arm/Group Description	Patients maintained on simultaneous V-V delay	V-V delay was optimized
Period Title: Overall Study
STARTED	49	44
COMPLETED	31	26
NOT COMPLETED	18	18

Baseline Characteristics

Arm/Group Title	Simultaneous Pacing V-V Timing	Sequential VV Pacing	Total
Arm/Group Description	Patients maintained on simultaneous V-V delay	V-V delay was optimized	Total of all reporting groups
Overall Participants	31	26	57
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 41.9%	15 57.7%	28 49.1%
>=65 years	18 58.1%	11 42.3%	29 50.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.2 (8.0)	62.4 (11.2)	65.6 (10.7)
Sex: Female, Male (Count of Participants)
Female	9 29%	5 19.2%	14 24.6%
Male	22 71%	21 80.8%	43 75.4%
Region of Enrollment (participants) [Number]
United States	31 100%	26 100%	57 100%

Outcome Measures

1. Primary Outcome

Title	CRT Responder Rate
Description	Patients underwent baseline NYHA class and 6-minute hall walk distance (6-MHWD) assessment. After device implantation AV delays were optimized and all patients were programmed to simultaneous biventricular (BiV) pacing. At the 3-month follow-up, the NYHA class and 6-MHWD were reassessed. Non-responders were randomized 1:1 to either sequential BiV pacing with VV optimization or simultaneous BiV pacing. The responder rate at 6 months post randomization was compared between the two groups. Which is why the numbers are broken further down in the Outcome Measure table.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Per protocol analysis.

Arm/Group Title	Simultaneous Pacing V-V Timing	Sequential VV Pacing
Arm/Group Description	Patients maintained on simultaneous V-V delay per protocol	V-V delay was optimized per protocol
Measure Participants	33	26
Responders	16 51.6%	20 76.9%
Non-Responders	17 54.8%	6 23.1%

2. Secondary Outcome

Title	NYHA Class Progression
Description	New York Heart Association (NYHA) functional classification provides a way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina pain.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Per protocol analysis

Arm/Group Title	Simultaneous Pacing V-V Timing	Sequential VV Pacing
Arm/Group Description	Patients maintained on simultaneous V-V delay	V-V delay was optimized
Measure Participants	30	26
NYYHA Class Improved by 1 category	11 35.5%	17 65.4%
NYHA Class Improved by more than 1 category	1 3.2%	1 3.8%
NYHA Class Unchanged	17 54.8%	7 26.9%
NYHA Class Worsened	1 3.2%	1 3.8%

3. Secondary Outcome

Title	6 Minute Hall Walk Distance Test (6-MHWD)
Description	Patients were considered non-responders if the 6-MHWD had not improved by greater than or equal to 10% compared to baseline. This statement is accurate and appropriate.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Simultaneous Pacing V-V Timing	Sequential VV Pacing
Arm/Group Description	Patients maintained on simultaneous V-V delay	V-V delay was optimized
Measure Participants	30	26
Responder	10 32.3%	13 50%
Non-Responder	20 64.5%	13 50%

4. Secondary Outcome

Title	Left Ventricular Ejection Fraction (LVEF)
Description	Ejection fraction is a measurement of the percentage of blood leaving your heart each time it contracts. The left ventricle is the heart's main pumping chamber, so ejection fraction is usually measured only in the left ventricle (LV).
Time Frame	Randomization and 9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Simultaneous Pacing V-V Timing	Sequential VV Pacing
Arm/Group Description	Patients maintained on simultaneous V-V delay	V-V delay was optimized
Measure Participants	30	26
Randomization	30.6 (10.5)	30.7 (10.5)
9 Month Follow-up Visit	32.6 (11.8)	32.1 (11.6)

Adverse Events

Arm/Group Title	Simultaneous Pacing V-V Timing		Sequential VV Pacing
Arm/Group Description	Patients maintained on simultaneous V-V delay		V-V delay was optimized
All Cause Mortality
	Simultaneous Pacing V-V Timing		Sequential VV Pacing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Simultaneous Pacing V-V Timing		Sequential VV Pacing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/31 (25.8%)		2/26 (7.7%)
Cardiac disorders
ONSET OF ATRIAL FIBRILLATION	1/31 (3.2%)	1	0/26 (0%)	0
RV Lead Dislodgment or Migration	1/31 (3.2%)	1	0/26 (0%)	0
RV Elevated Pacing Thresholds	1/31 (3.2%)	1	0/26 (0%)	0
RV Decreased R/P-Wave Amplitude/Loss of Sensing	1/31 (3.2%)	1	0/26 (0%)	0
LV Loss of capture	1/31 (3.2%)	1	0/26 (0%)	0
Therapy/Aborted Therapy for Non-Ventricular Rhythm:AF/AFL	1/31 (3.2%)	1	0/26 (0%)	0
MULTIPLE ICD FIRING, NSTEMI	1/31 (3.2%)	1	0/26 (0%)	0
CHEST PAIN AND AICD FIRING	1/31 (3.2%)	1	0/26 (0%)	0
Infections and infestations
BACTEREMIA	0/31 (0%)	0	1/26 (3.8%)	1
Nervous system disorders
LEFT BRAIN TIA	0/31 (0%)	0	1/26 (3.8%)	1
Other (Not Including Serious) Adverse Events
	Simultaneous Pacing V-V Timing		Sequential VV Pacing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/31 (22.6%)		12/26 (46.2%)
Blood and lymphatic system disorders
ANEMIA	0/31 (0%)	0	1/26 (3.8%)	1
Cardiac disorders
DIAPHRAGMATIC CAPTURE BY ATRIAL LEAD	1/31 (3.2%)	1	0/26 (0%)	0
CHF EXACERBATION	0/31 (0%)	0	1/26 (3.8%)	1
CHF EXACERBATION + NEAR SYNCOPE	0/31 (0%)	0	1/26 (3.8%)	1
SHORTNESS OF BREATH	0/31 (0%)	0	1/26 (3.8%)	1
NEAR SYNCOPE WITH GENERAL WEAKNESS	1/31 (3.2%)	1	0/26 (0%)	0
HOSPITALIZATION FOR WEAKNESS WITH ICD FIRING X 2	0/31 (0%)	0	1/26 (3.8%)	1
HOSPITALIZATION FOR NEAR SYNCOPE	0/31 (0%)	0	1/26 (3.8%)	1
ACUTE VIRAL PERICARDITIS	0/31 (0%)	0	1/26 (3.8%)	1
ABDOMINAL AORTIC ANEURYSM	1/31 (3.2%)	1	0/26 (0%)	0
SYNCOPE	1/31 (3.2%)	1	0/26 (0%)	0
COPD (CHRONIC)	1/31 (3.2%)	1	0/26 (0%)	0
EXACERBATION CONGESTIVE HEART FAILURE	0/31 (0%)	0	1/26 (3.8%)	1
General disorders
DIZZY SPELL	1/31 (3.2%)	1	0/26 (0%)	0
SINUS INFECTION	1/31 (3.2%)	1	0/26 (0%)	0
Infections and infestations
MRSA INFECTED LEFT ARM DIALYSIS GRAFT	0/31 (0%)	0	1/26 (3.8%)	1
Renal and urinary disorders
PNEUMONIA AND WORSENING KIDNEY FUNCTION	0/31 (0%)	0	1/26 (3.8%)	1
END STAGE RENAL DZ - (WORSENING OF KNOWN DISEASE)	0/31 (0%)	0	1/26 (3.8%)	1
WORSENING RENAL FUNCTION	0/31 (0%)	0	1/26 (3.8%)	1

Limitations/Caveats

Due to the lower than expected non-responder rate at 3 months, the study did not reach the target randomized sample size.

More Information

Certain Agreements

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

Publications and presentation should be presented to sponsor 30 days (manuscripts) or 7 days (abstracts) prior to submission for publication. The sponsor reserves the right to deny submission of study results if based on data owned by sponsor.