FIX-HF-5CA: Continued Access Protocol for the Evaluation of the OPTIMIZER Smart System

• Sponsor: Impulse Dynamics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03102437
• Collaborator: (none)
• Enrollment: 106
• Locations: 17
• Arm: 1
• Actual Duration (Months): 29.5
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a multicenter, prospective, single-arm Continued Access study of the Optimizer Smart System with CCM therapy.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Congestive Heart Failure; Chronic Heart Disease; CHF	Device: Optimizer Smart System	N/A

Detailed Description

The Continued Access study is a prospective, non-randomized, multi-center study designed to allow controlled access to the Optimizer Smart System until the PMA order has been issued by the FDA.

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Continued AccessContinued Access
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: FIX-HF-5CA: Continued Access Protocol for the Evaluation of the OPTIMIZER Smart System in Subjects With Moderate-to-Severe Heart Failure With Ejection Fraction Between 25% and 45%
• Actual Study Start Date: Jul 1, 2017
• Actual Primary Completion Date: Dec 16, 2019
• Actual Study Completion Date: Dec 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Optimizer Smart System All eligible subjects will have the Optimizer Smart System implanted and receive cardiac contractility modulation therapy (CCM).	Device: Optimizer Smart System; The Optimizer Smart System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.

Outcome Measures

Primary Outcome Measures

1. Observed Mortality Comparison to the Predicted Probability of Mortality [2 years 6 months]

   The FIX-HF-5CA Study was unofficially intended to serve as the Post-Approval Study (PAS) with the intention of collecting 3 year observed mortality data and comparing that to the predicted probability of mortality derived from two validated heart failure models [MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and SHFM (Seattle Heart Failure Model)]. The objective was to show that the observed prevalence of mortality was not worse than the derived predicted probability of mortality. Upon PMA and PMA Supplement approval of the device, however, FDA and the Sponsor stopped this 5CA study and a new PAS was initiated (NCT03970343). No long-term mortality data or final analysis was collected for this study.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Subjects who are 18 years of age or older

2. Subjects who have a baseline ejection fraction greater than or equal to 25% and less than or equal to 45% by echocardiography.

3. Subjects who, in the opinion of the Investigator (based on the current guidelines for clinical practice), have been treated for heart failure for at least 90 days and are currently receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure.

4. Subjects who are in New York Heart Association functional Class III and IV at the time of enrollment.

5. Subjects who are willing and able to return for all follow-up visits.

Exclusion Criteria:

1. Subjects who have a potentially correctible cause of heart failure, such as valvular heart disease or congenital heart disease.

2. Subjects receiving any form of inotropic support within 30 days before enrollment, including subjects on continuous IV inotrope therapy.

3. Subjects hospitalized for decompensated heart failure requiring acute treatment with intravenous loop diuretics, IV inotropes or hemofiltration within 30 days before enrollment and baseline testing.

4. Subjects who have a clinically significant amount of ambient ectopy, defined as more than 8,900 PVCs per 24 hours on baseline Holter monitoring.

5. Subjects having a PR interval greater than 375ms.

6. Subjects who are scheduled for a CABG or a PTCA procedure, or who have undergone a CABG procedure within 90 days or a PTCA procedure within 30 days of enrollment.

7. Subjects who have a biventricular pacing system, an accepted indication for such a device, or a QRS width of 130ms or greater.

8. Subjects who have had a myocardial infarction within 90 days of enrollment.

9. Subjects who have mechanical tricuspid valve.

10. Subjects who have a Left Ventricular Assist Device or prior heart transplant.

11. Subjects on dialysis.

12. Subjects who are participating in another experimental protocol.

13. Subjects who are unable to provide informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chan Heart Rhythm Institute	Mesa	Arizona	United States	85206
2	Southwest Cardiology Associates	Mesa	Arizona	United States	85206
3	Cardiovascular Consultants	Phoenix	Arizona	United States	85027
4	Arizona Arrhythmia Consultants	Scottsdale	Arizona	United States	85251
5	Pima Heart	Tucson	Arizona	United States	85745
6	Baptist Health Lexington	Lexington	Kentucky	United States	40503
7	University of Kentucky	Lexington	Kentucky	United States	40536
8	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
9	Cooper University Hospital	Camden	New Jersey	United States	08103
10	Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
11	St. Mary Research Institute	Langhorne	Pennsylvania	United States	19047
12	Jefferson Heart Institute	Philadelphia	Pennsylvania	United States	19047
13	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
14	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania	United States	19104
15	Guthrie Medical Group at Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
16	UT Southwestern Medical Center	Dallas	Texas	United States	75390
17	CHRISTUS Trinity Mother Frances Health System	Tyler	Texas	United States	75701

Sponsors and Collaborators

• Impulse Dynamics

Investigators

• Study Director: Daniel Burkhoff, MD, PhD, Impulse Dynamics

Study Documents (Full-Text)

• Study Protocol and Informed Consent Form - Mar 27, 2019

More Information

Publications

None provided.

• Responsible Party: Impulse Dynamics
• ClinicalTrials.gov Identifier: NCT03102437
• Other Study ID Numbers: CP OPT2017-004
• First Posted: Apr 5, 2017
• Last Update Posted: Nov 23, 2021
• Last Verified: Feb 1, 2021

• 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
• Keywords provided by Impulse Dynamics: Cardiac Contractility Modulation; CCM; FIX-HF-5CA; Continued Access
• Additional relevant MeSH terms: Heart Failure; Heart Diseases

Study Results

Participant Flow

Arm/Group Title	Optimizer Smart System (3-Lead)	Optimizer Smart System (2-Lead)
Arm/Group Description	All eligible subjects will have the Optimizer Smart System 3-Lead implanted and receive cardiac contractility modulation therapy (CCM). Optimizer Smart System: The Optimizer Smart System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.	All eligible subjects will have the Optimizer Smart System 2-Lead implanted and receive cardiac contractility modulation therapy (CCM). Optimizer Smart System: The Optimizer Smart System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.
Period Title: Overall Study
STARTED	70	36
COMPLETED	65	36
NOT COMPLETED	5	0

Baseline Characteristics

Arm/Group Title	Optimizer Smart System (3-Lead)	Optimizer Smart System (2-Lead)	Total
Arm/Group Description	All eligible subjects will have the Optimizer Smart System 3-Lead implanted and receive cardiac contractility modulation therapy (CCM). Optimizer Smart System: The Optimizer Smart System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.	All eligible subjects will have the Optimizer Smart System 2-Lead implanted and receive cardiac contractility modulation therapy (CCM). Optimizer Smart System: The Optimizer Smart System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.	Total of all reporting groups
Overall Participants	70	36	106
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	65	66	66
Sex: Female, Male (Count of Participants)
Female	26 37.1%	10 27.8%	36 34%
Male	44 62.9%	26 72.2%	70 66%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.4%	0 0%	1 0.9%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	9 12.9%	5 13.9%	14 13.2%
White	59 84.3%	30 83.3%	89 84%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.4%	1 2.8%	2 1.9%
Region of Enrollment (Count of Participants)
United States	70 100%	36 100%	106 100%

Outcome Measures

1. Primary Outcome

Title	Observed Mortality Comparison to the Predicted Probability of Mortality
Description	The FIX-HF-5CA Study was unofficially intended to serve as the Post-Approval Study (PAS) with the intention of collecting 3 year observed mortality data and comparing that to the predicted probability of mortality derived from two validated heart failure models [MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and SHFM (Seattle Heart Failure Model)]. The objective was to show that the observed prevalence of mortality was not worse than the derived predicted probability of mortality. Upon PMA and PMA Supplement approval of the device, however, FDA and the Sponsor stopped this 5CA study and a new PAS was initiated (NCT03970343). No long-term mortality data or final analysis was collected for this study.
Time Frame	2 years 6 months

Outcome Measure Data

Analysis Population Description

All subjects implanted with the Optimizer System.

Arm/Group Title	Optimizer Smart System (3-Lead)	Optimizer Smart System (2-Lead)
Arm/Group Description	All eligible subjects will have the Optimizer Smart System 3-Lead implanted and receive cardiac contractility modulation therapy (CCM). Optimizer Smart System: The Optimizer Smart System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.	All eligible subjects will have the Optimizer Smart System 2-Lead implanted and receive cardiac contractility modulation therapy (CCM). Optimizer Smart System: The Optimizer Smart System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.
Measure Participants	70	36
Count of Participants [Participants]	5 7.1%	0 0%

Adverse Events

Time Frame	24 Months
Arm/Group Title	Optimizer Smart System (3-Lead)		Optimizer Smart System (2-Lead)
Arm/Group Description	All eligible subjects will have the Optimizer Smart System 3-Lead implanted and receive cardiac contractility modulation therapy (CCM). Optimizer Smart System: The Optimizer Smart System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.		All eligible subjects will have the Optimizer Smart System 2-Lead implanted and receive cardiac contractility modulation therapy (CCM). Optimizer Smart System: The Optimizer Smart System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.
All Cause Mortality
	Optimizer Smart System (3-Lead)		Optimizer Smart System (2-Lead)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/70 (7.1%)		0/36 (0%)
Serious Adverse Events
	Optimizer Smart System (3-Lead)		Optimizer Smart System (2-Lead)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/70 (18.6%)		4/36 (11.1%)
Cardiac disorders
ICD or pacemaker System AE	1/70 (1.4%)	1	0/36 (0%)	0
Arrhythmias	2/70 (2.9%)	2	0/36 (0%)	0
General Cardiopulmonary event	2/70 (2.9%)	2	1/36 (2.8%)	1
Worsening Heart Failure	2/70 (2.9%)	2	0/36 (0%)	0
General disorders
General Medical	2/70 (2.9%)	2	0/36 (0%)	0
Infections and infestations
Optimizer Pocket infection	1/70 (1.4%)	1	0/36 (0%)	0
Localized Infection	1/70 (1.4%)	1	0/36 (0%)	0
Nervous system disorders
Neurologic Dysfunction - TIA	1/70 (1.4%)	1	1/36 (2.8%)	1
Surgical and medical procedures
Optimizer Lead dislodgement	2/70 (2.9%)	3	2/36 (5.6%)	2
Other (Not Including Serious) Adverse Events
	Optimizer Smart System (3-Lead)		Optimizer Smart System (2-Lead)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/70 (17.1%)		3/36 (8.3%)
Blood and lymphatic system disorders
Bleeding	2/70 (2.9%)	2	0/36 (0%)	0
Thromboembolism (non-Neurologic)	1/70 (1.4%)	1	0/36 (0%)	0
Cardiac disorders
General Cardiopulmonary Event	1/70 (1.4%)	1	1/36 (2.8%)	1
General disorders
General Medical	8/70 (11.4%)	9	1/36 (2.8%)	1
Surgical and medical procedures
OPTIMIZER pocket stimulation	1/70 (1.4%)	1	0/36 (0%)	0
ICD inappropriate therapy	0/70 (0%)	0	1/36 (2.8%)	1

Limitations/Caveats

The FIX-HF-5CA Study was unofficially intended to serve as the Post-Approval Study (PAS) with the intention of collecting 3 year data. Upon PMA (3-lead) and PMA Supplement approval (2-lead) of the device, however, FDA and the Sponsor terminated this continued access study and a new PAS was initiated (NCT03970343). No long-term or final analysis was collected for this study.

More Information

Certain Agreements

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

The Publication Committee shall consist of the National PIs and Impulse Dynamics representatives. All abstracts and papers of the multi-center publications will be reviewed by members of the publication committee and all authors. When appropriate, the publication committee will collect comments and resolve final draft issues. If a paper is rejected, the publication committee and its authors will decide the next course of action.