FREEDOM - A Frequent Optimization Study Using the QuickOpt Method

• Sponsor: Abbott Medical Devices (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00418314
• Collaborator: (none)
• Enrollment: 1,647
• Locations: 2
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 823.5
• Patients Per Site Per Month: 23.5

Study Details

Study Description

Brief Summary

The objective of this study is to demonstrate that frequent atrio-ventricular (AV/PV) and inter-ventricular (V-V) delay optimization using QuickOpt in patients with cardiac resynchronization therapy device results in improved clinical response over standard of care (i.e. empiric programming or one-time optimization using any non-intracardiac electrogram optimization methods).

Condition or Disease	Intervention/Treatment	Phase
Cardiac Arrhythmias; Heart Failure	Device: Control; Device: QuickOpt	N/A

Detailed Description

• This is a prospective, double-blinded, multicenter, randomized study

• Patient could be enrolled up to 2 weeks post CRT-D implant and are followed for 12 months post implant with follow-up visits at 3, 6, 9 and 12 months

• Patients will be randomized at enrollment to either Group 1 ("QuickOpt Group") or Group 2 ("Control Group").

• Group 1 - The patient's device is programmed to sequential biventricular pacing mode with AV/PV and VV delays optimized using QuickOpt. For Group 1 patients, optimization using QuickOpt is performed at enrollment, 3 month, 6 month, 9 month, 12 month and at any unscheduled follow-up visits.

• Group 2 - The patient's device is programmed to either simultaneous or sequential BiV pacing mode as per physician's discretion. The AV/PV and inter-ventricular (VV) delays could be programmed empirically or optimized using any non-IEGM based method as per sites standard of care. However, the Group 2 patients can be optimized only once within the first 4 weeks post implant. Any AV/PV and VV delay optimizations performed after 4 weeks post implant in Group 2 patients will be considered protocol deviations.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1647 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: FREEDOM - A Frequent Optimization Study Using the QuickOpt Method
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QuickOpt (Treatment) Frequent optimization using QuickOpt to optimize the AV/PV and VV Delays.	Device: QuickOpt; Frequent optimization using QuickOpt to optimize AV/PV and VV delays.
Active Comparator: Control Empiric programming or one-time optimization using a non-IEGM method.	Device: Control; Empiric programming or one-time optimization using a non-IEGM method.

Outcome Measures

Primary Outcome Measures

1. Heart Failure Clinical Composite Score [12 months]

   The clinical composite score classifies each randomized patient as improved, unchanged, or worse depending on the clinical response during and the clinical status at the end of the trial. Patients are considered improved if at the final visit they experienced a favorable change in NYHA functional class or in the patient global assessment (or both) but did not experience any major adverse clinical events during the course of the trial. Patients are considered worse if they experienced a major clinical event during the study duration or reported worsening of their NYHA class or global assessment at the final visit. Patients are considered unchanged if they are neither improved nor worse.

Secondary Outcome Measures

1. All-cause, Cardiovascular and Heart Failure Mortality; [12 months]

2. All Cause, Cardiovascular and Heart Failure Hospitalization [12 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient meets current CRT-D indications and be implanted with a St. Jude Medical (SJM) CRT¬D device with VV timing and a compatible lead system.

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

• Patient has the ability to independently comprehend and complete a QOL questionnaire.

Exclusion Criteria:

• Patient has an epicardial ventricular lead system.

• Patient has the ability to walk ≥ 450 meters in 6 minutes

• Patient has limited intrinsic atrial activity (≤ 40 bpm).

• Patient has persistent or permanent atrial fibrillation (AF).

• Patient has a 2° or 3° heart block.

• Patient's life expectancy is less than 1 year.

• Patient is pregnant.

• Patient is on IV inotropic agents.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai Hospital	Los Angeles	California	United States	90048
2	Ohio State Univeristy	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Abbott Medical Devices

Investigators

• Principal Investigator: William Abraham, MD, Ohio State University, Columbus, OH, USA
• Principal Investigator: Daniel Gras, MD, Nouvelles Cliniques Nantaises, Nantes, France

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abbott Medical Devices
• ClinicalTrials.gov Identifier: NCT00418314
• Other Study ID Numbers: CRD378
• First Posted: Jan 4, 2007
• Last Update Posted: Feb 19, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Arrhythmias, Cardiac

Study Results

Participant Flow

Arm/Group Title	QuickOpt (Treatment)	Control
Arm/Group Description	Frequent optimization using QuickOpt to optimize the AV/PV and VV Delays.	Empiric programming or one-time optimization using a non-IEGM method.
Period Title: Overall Study
STARTED	817	830
COMPLETED	816	828
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	QuickOpt (Treatment)	Control	Total
Arm/Group Description	Frequent optimization using QuickOpt to optimize the AV/PV and VV Delays.	Empiric programming or one-time optimization using a non-IEGM method.	Total of all reporting groups
Overall Participants	817	830	1647
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	307 37.6%	340 41%	647 39.3%
>=65 years	510 62.4%	490 59%	1000 60.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.8 (11)	66.7 (11)	66.7 (11)
Sex: Female, Male (Count of Participants)
Female	196 24%	238 28.7%	434 26.4%
Male	621 76%	592 71.3%	1213 73.6%
Region of Enrollment (participants) [Number]
United States	482 59%	487 58.7%	969 58.8%
Europe	282 34.5%	288 34.7%	570 34.6%
Canada	32 3.9%	35 4.2%	67 4.1%
Australia	17 2.1%	15 1.8%	32 1.9%
Middle East	3 0.4%	4 0.5%	7 0.4%
Southeast Asia	1 0.1%	1 0.1%	2 0.1%

Outcome Measures

1. Primary Outcome

Title	Heart Failure Clinical Composite Score
Description	The clinical composite score classifies each randomized patient as improved, unchanged, or worse depending on the clinical response during and the clinical status at the end of the trial. Patients are considered improved if at the final visit they experienced a favorable change in NYHA functional class or in the patient global assessment (or both) but did not experience any major adverse clinical events during the course of the trial. Patients are considered worse if they experienced a major clinical event during the study duration or reported worsening of their NYHA class or global assessment at the final visit. Patients are considered unchanged if they are neither improved nor worse.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	QuickOpt (Treatment)	Control
Arm/Group Description	Frequent optimization using QuickOpt to optimize the AV/PV and VV Delays.	Empiric programming or one-time optimization using a non-IEGM method.
Measure Participants	816	828
Improved	551 67.4%	559 67.3%
Unchanged	76 9.3%	86 10.4%
Worsened	189 23.1%	183 22%

2. Secondary Outcome

Title	All-cause, Cardiovascular and Heart Failure Mortality;
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	QuickOpt (Treatment)	Control
Arm/Group Description	Frequent optimization using QuickOpt to optimize the AV/PV and VV Delays.	Empiric programming or one-time optimization using a non-IEGM method.
Measure Participants	816	828
Number [participants]	44 5.4%	42 5.1%

3. Secondary Outcome

Title	All Cause, Cardiovascular and Heart Failure Hospitalization
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	QuickOpt (Treatment)	Control
Arm/Group Description	Frequent optimization using QuickOpt to optimize the AV/PV and VV Delays.	Empiric programming or one-time optimization using a non-IEGM method.
Measure Participants	816	828
Number [participants]	294 36%	303 36.5%

Adverse Events

Arm/Group Title	QuickOpt (Treatment)		Control
Arm/Group Description	Frequent optimization using QuickOpt to optimize the AV/PV and VV Delays.		Empiric programming or one-time optimization using a non-IEGM method.
All Cause Mortality
	QuickOpt (Treatment)		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	QuickOpt (Treatment)		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	120/816 (14.7%)		111/828 (13.4%)
Cardiac disorders
Coronary Angiogram	1/816 (0.1%)	1	1/828 (0.1%)	1
Cardiopulmonary Arrest	2/816 (0.2%)	2	1/828 (0.1%)	1
Arrhythmias	11/816 (1.3%)	12	10/828 (1.2%)	10
Cardiac Perforation	2/816 (0.2%)	2	5/828 (0.6%)	5
Thrombosis	0/816 (0%)	0	3/828 (0.4%)	3
Chest pain/MI	7/816 (0.9%)	10	9/828 (1.1%)	10
Coronary Sinus Dissection	1/816 (0.1%)	1	0/828 (0%)	0
Death	8/816 (1%)	8	7/828 (0.8%)	7
Device migration/malfunction	0/816 (0%)	0	2/828 (0.2%)	3
Elevated Pacing Thresholds	10/816 (1.2%)	10	3/828 (0.4%)	3
Erosion/Pocket Pain	4/816 (0.5%)	4	2/828 (0.2%)	2
Hematoma	4/816 (0.5%)	4	7/828 (0.8%)	7
Infection	10/816 (1.2%)	10	14/828 (1.7%)	15
Lead Dislodgment/Migration	40/816 (4.9%)	45	35/828 (4.2%)	44
Lead Fracture/Insulation Damage	3/816 (0.4%)	3	0/828 (0%)	0
Oversensing/Undersensing	16/816 (2%)	18	8/828 (1%)	9
Phrenic Nerve/Diaphragmatic Nerve Stimulation	11/816 (1.3%)	12	6/828 (0.7%)	7
Therapy for non-ventricular rhythm	0/816 (0%)	0	3/828 (0.4%)	3
Valve replacement	0/816 (0%)	0	2/828 (0.2%)	2
Other cardiac	4/816 (0.5%)	4	3/828 (0.4%)	3
Endocrine disorders
Endocrine disorders	2/816 (0.2%)	2	0/828 (0%)	0
Gastrointestinal disorders
Rectal Bleeding	1/816 (0.1%)	1	0/828 (0%)	0
Musculoskeletal and connective tissue disorders
Joint pain	3/816 (0.4%)	3	5/828 (0.6%)	5
Nervous system disorders
CVA/TIA	2/816 (0.2%)	2	2/828 (0.2%)	2
Neurologic other	1/816 (0.1%)	1	1/828 (0.1%)	2
Respiratory, thoracic and mediastinal disorders
Respiratory Arrest	2/816 (0.2%)	2	4/828 (0.5%)	4
Pleural Effusion	3/816 (0.4%)	4	3/828 (0.4%)	3
Respiratory other	2/816 (0.2%)	2	2/828 (0.2%)	2
Vascular disorders
DVT	3/816 (0.4%)	3	6/828 (0.7%)	9
Other (Not Including Serious) Adverse Events
	QuickOpt (Treatment)		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	184/816 (22.5%)		177/828 (21.4%)
Cardiac disorders
Cardiopulmonary Arrest	2/816 (0.2%)	2	4/828 (0.5%)	4
Arrhythmias	65/816 (8%)	83	55/828 (6.6%)	63
Elevated Pacing Thresholds	10/816 (1.2%)	13	3/828 (0.4%)	3
Undersensing/Oversensing	14/816 (1.7%)	16	11/828 (1.3%)	14
Heart Failure	61/816 (7.5%)	95	43/828 (5.2%)	63
Hematoma	7/816 (0.9%)	7	13/828 (1.6%)	13
Infection	4/816 (0.5%)	5	3/828 (0.4%)	3
Lead Dislodgement/Migration	14/816 (1.7%)	16	17/828 (2.1%)	20
MI	2/816 (0.2%)	2	5/828 (0.6%)	5
Phrenic Nerve/Diaphragmatic Nerve Stimulation	36/816 (4.4%)	47	30/828 (3.6%)	34
Therapy for non-ventricular rhythm	5/816 (0.6%)	6	16/828 (1.9%)	16
Nervous system disorders
Syncope	8/816 (1%)	9	10/828 (1.2%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Publications and presentations proposed by participating centers should be furnished to sponsor for review and comment 30 days (manuscripts) or 7 days (abstracts) prior to submission for publication. Sponsor reserves the right to deny submission of study results if based on data owned by sponsor.