I-70: Efficacy and Safety of Implantable Cardioverter-Defibrillator (ICD) Implantation in the Elderly

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Terminated
• CT.gov ID: NCT02121158
• Collaborator: (none)
• Enrollment: 167
• Locations: 5
• Arms: 2
• Actual Duration (Months): 63
• Patients Per Site: 33.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The overall aim of this trial is to study the safety and efficacy of ICD implantation as a primary prevention strategy of sudden cardiac death in patients 70 years and older. This study will assess the many competing factors involved with ICD implantation including 1) the impact on mortality, especially in the context of a declining rate of sudden death with advanced age, 2) the tolerability of the powerful therapeutic action of the device, and 3) the impact on quality of life.

Condition or Disease	Intervention/Treatment	Phase
Cardiomyopathy; Coronary Artery Disease; Congestive Heart Failure; Myocardial Infarction	Device: Implantable Cardioverter Defibrillator; Other: Optimal Medical Therapy	N/A

Detailed Description

The overall aim of this trial is to study the safety and efficacy of ICD implantation as a primary prevention strategy of sudden cardiac death (SCD) in patients 70 years and older. In particular, this study is designed to determine the comparative effectiveness of ICD, in addition to optimal medical therapy (OMT), in reducing all-cause mortality, versus OMT alone; OMT includes standard intervention for chronic heart failure patients, i.e. lifestyle modification, disease management, adoption of healthy diet and exercise practices, etcetera. One particularly important secondary objective is to assess treatment efficacy under the conditions of high versus low co-morbidity burden.

Participants will be randomized (1:1 ratio) to ICD + OMT or OMT alone, and stratified by participating site and co-morbidity level (Charlson score <3 versus 3+). Acute treatment visits will occur as clinically indicated and per local convention; follow-up will occur 1-4 months post-randomization (all participants), and not sooner than 30 days - and not later than 120 days post-implantation (ICD arm); regular follow-up will occur at 6 month intervals post-randomization until study close (all participants). All follow-up will be conducted centrally. Neither the participant nor treating clinician will be masked to treatment.

Primary Objective:

The primary objective of this study is to determine if a primary prevention strategy with ICD implantation in addition to optimal medical therapy (OMT) is effective in reducing all-cause mortality compared to OMT alone in patients 70 years of age and older who are eligible for ICD therapy according to current Centers for Medicare & Medicaid Services (CMS) criteria.

Primary Hypothesis:

The primary hypothesis of this study is that implantation of an ICD plus optimal medical therapy will reduce all-cause mortality in patients 70 years of age and older versus optimal medical therapy alone.

Secondary Objectives:

1. One secondary objective of this study is to ascertain whether age, co-morbidity burden, or age and burden together, are determinants in mortality outcomes in the OMT versus ICD

• OMT group.

1. An additional secondary objective of the study is to determine the effect of ICD implantation plus optimal medical therapy on quality of life among elderly patients compared with optimal medical therapy alone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 167 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CSP #592 - Efficacy and Safety of ICD Implantation in the Elderly
• Actual Study Start Date: Aug 7, 2015
• Actual Primary Completion Date: Nov 6, 2020
• Actual Study Completion Date: Nov 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: 1 ICD implantation in addition to Optimal Medical Therapy	Device: Implantable Cardioverter Defibrillator; The ICD and lead(s) will be FDA-approved.
Active Comparator: 2 Optimal Medical Therapy	Other: Optimal Medical Therapy; Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke.

Outcome Measures

Primary Outcome Measures

1. Mortality [Through study completion, starting from consent/baseline: average of 31 months.]

   All-cause mortality

Secondary Outcome Measures

1. Quality of Life - Minnesota Living With Heart Failure Questionnaire [Measured at 12-months post-randomization]

   Minnesota Living with Heart Failure questionnaire. MLHF scoring: 0 points = Best QOL, 105 points = Worst QOL.

2. Sudden Cardiac Death [Through study completion, starting from consent/baseline: average of 31 months.]

   Sudden Cardiac Death

3. All-cause Hospitalization [Through study completion, starting from consent/baseline: average of 31 months.]

   Number of participants hospitalized during study follow-up

Eligibility Criteria

Criteria

• Ages Eligible for Study: 70 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 70 years of age or older

2. Eligible for ICD implementation according to the CMS criteria for primary prevention by one of the following conditions:

3. Documented prior MI and a measured left ventricular ejection fraction (LVEF) <=30% (includes New York Heart Association [NYHA] class I, II, or III)

4. Coronary artery disease with a documented prior MI, a measured left ventricular ejection fraction <=35%, and inducible, sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) at electrophysiology (EP) study

5. Ischemic dilated cardiomyopathy (IDCM), documented prior MI, NYHA class II and III heart failure, and measured LVEF <=35%

6. Non-ischemic dilated cardiomyopathy (NIDCM) > 3 months, NYHA Class II and III heart failure, and measured LVEF <=35%

7. Stable condition on Optimal Medical Therapy

8. Able and willing to provide informed consent to participate in this study

Exclusion Criteria:

1. Enrolled in or planning to enroll in a conflicting trial

2. Receiving a bi-ventricular ICD device

3. New York Heart Association class IV heart failure

4. Cardiogenic shock or symptomatic hypotension while in stable baseline rhythm,

5. Coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) within the past 3 months

6. An MI within the past 40 days

7. Clinical symptoms or findings that would make them a candidate for coronary revascularization

8. Irreversible brain damage from pre-existing cerebral disease

9. Any disease other than cardiac disease (e.g. cancer, uremia, liver failure), associated with a likelihood of survival less than 1 year

10. Circumstance that would prevent completion of the trial and follow-up activities, including medical condition

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington DC VA Medical Center, Washington, DC	Washington	District of Columbia	United States	20422
2	North Florida/South Georgia Veterans Health System, Gainesville, FL	Gainesville	Florida	United States	32608
3	Minneapolis VA Health Care System, Minneapolis, MN	Minneapolis	Minnesota	United States	55417
4	VA Portland Health Care System, Portland, OR	Portland	Oregon	United States	97239
5	Tennessee Valley Healthcare System Nashville Campus, Nashville, TN	Nashville	Tennessee	United States	37212-2637

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Study Chair: Steve Singh, MD, Washington DC VA Medical Center, Washington, DC

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jun 17, 2016

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02121158
• Other Study ID Numbers: 592
• First Posted: Apr 23, 2014
• Last Update Posted: Jan 20, 2022
• Last Verified: Dec 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
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: CSP 592; ICD; cardiovascular; heart; aging; chronic diseases; multi-site trial; investigational device; cardiomyopathy; coronary artery disease; congestive heart failure; myocardial infarction; I-70; I70; elderly; defibrillator
• Additional relevant MeSH terms: Heart Failure; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Myocardial Infarction; Cardiomyopathies; Infarction

Study Results

Participant Flow

Recruitment Details	Recruitment at six Department of Veterans Affairs Medical Centers (VAMCs). Recruitment start: 8/6/2015 (4) 9/25/2015 (1) and 10/29/2015 (1). Recruitment terminated: 12/6/2016 (1) and 12/5/2019 (5).
Pre-assignment Detail	None: Study design did not include significant events that occur after participant enrollment: no run-in phase, nor wash-out.

Arm/Group Title	Optimal Medical Therapy	Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)
Arm/Group Description	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke.	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke + FDA-Approved implantable cardioverter defibrillator and leads.
Period Title: Overall Study
STARTED	85	82
COMPLETED	85	82
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Optimal Medical Therapy	Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)	Total
Arm/Group Description	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke.	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke + FDA-Approved implantable cardioverter defibrillator and leads.	Total of all reporting groups
Overall Participants	85	82	167
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	85 100%	82 100%	167 100%
Sex: Female, Male (Count of Participants)
Female	1 1.2%	1 1.2%	2 1.2%
Male	84 98.8%	81 98.8%	165 98.8%
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	12 14.1%	15 18.3%	27 16.2%
White	73 85.9%	67 81.7%	140 83.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	85 100%	82 100%	167 100%
New York Heart Association Class: I (Count of Participants)
Count of Participants [Participants]	2 2.4%	4 4.9%	6 3.6%
New York Heart Association Class: II (Count of Participants)
Count of Participants [Participants]	62 72.9%	58 70.7%	120 71.9%
New York Heart Association Class: III (Count of Participants)
Count of Participants [Participants]	21 24.7%	20 24.4%	41 24.6%
New York Heart Association Class: IV (Count of Participants)
Count of Participants [Participants]	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Mortality
Description	All-cause mortality
Time Frame	Through study completion, starting from consent/baseline: average of 31 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optimal Medical Therapy	Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)
Arm/Group Description	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke.	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke + FDA-Approved implantable cardioverter defibrillator and leads.
Measure Participants	85	82
Count of Participants [Participants]	23 27.1%	20 24.4%

2. Secondary Outcome

Title	Quality of Life - Minnesota Living With Heart Failure Questionnaire
Description	Minnesota Living with Heart Failure questionnaire. MLHF scoring: 0 points = Best QOL, 105 points = Worst QOL.
Time Frame	Measured at 12-months post-randomization

Outcome Measure Data

Analysis Population Description

Analysis population differs from total number of study participants due to non-completion of the 12-month study visit, explained by either patient expiry or missed visit.

Arm/Group Title	Optimal Medical Therapy	Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)
Arm/Group Description	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke.	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke + FDA-Approved implantable cardioverter defibrillator and leads.
Measure Participants	62	63
Median (Inter-Quartile Range) [score on a scale]	11	13

3. Secondary Outcome

Title	Sudden Cardiac Death
Description	Sudden Cardiac Death
Time Frame	Through study completion, starting from consent/baseline: average of 31 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optimal Medical Therapy	Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)
Arm/Group Description	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke.	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke + FDA-Approved implantable cardioverter defibrillator and leads.
Measure Participants	85	82
Count of Participants [Participants]	5 5.9%	3 3.7%

4. Secondary Outcome

Title	All-cause Hospitalization
Description	Number of participants hospitalized during study follow-up
Time Frame	Through study completion, starting from consent/baseline: average of 31 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optimal Medical Therapy	Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)
Arm/Group Description	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke.	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke + FDA-Approved implantable cardioverter defibrillator and leads.
Measure Participants	85	82
Count of Participants [Participants]	61 71.8%	60 73.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Optimal Medical Therapy, Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)
	Comments
	Type of Statistical Test	Equivalence
	Comments	Unadjusted
Statistical Test of Hypothesis	p-Value	0.7457
	Comments
	Method	Cox Proportional Hazards
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.915
	Confidence Interval	(2-Sided) 95%; 0.534 to 1.568
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Serious Adverse Events were monitored from consent/baseline through 30 days after study exit, an average of 31 months. Non-Serious Adverse Events were monitored from consent/baseline through 30 days (30 days only, i.e. 30 days past consent [OMT arm] or 30 days past implantation [ICD arm]), i.e. 30 days for all participants.
Arm/Group Title	Optimal Medical Therapy		Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)
Arm/Group Description	Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke.		Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke + FDA-Approved implantable cardioverter defibrillator and leads.
All Cause Mortality
	Optimal Medical Therapy		Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/85 (27.1%)		20/82 (24.4%)
Serious Adverse Events
	Optimal Medical Therapy		Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/85 (78.8%)		62/82 (75.6%)
Cardiac disorders
Myocardial Infarction	12/85 (14.1%)		8/82 (9.8%)
Atrial fibrillation / Atrial flutter	9/85 (10.6%)		2/82 (2.4%)
HF Complication	57/85 (67.1%)		54/82 (65.9%)
Infections and infestations
Infection (ICD)	1/85 (1.2%)		0/82 (0%)
Infection (other)	26/85 (30.6%)		32/82 (39%)
Metabolism and nutrition disorders
Bleeding	0/85 (0%)		1/82 (1.2%)
Nervous system disorders
Stroke	2/85 (2.4%)		3/82 (3.7%)
Product Issues
Lead Alteration	1/85 (1.2%)		0/82 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/85 (0%)		1/82 (1.2%)
Other (Not Including Serious) Adverse Events
	Optimal Medical Therapy		Optimal Medical Therapy + Implantable Cardioverter Defibrillator (OMT + ICD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/85 (1.2%)		6/82 (7.3%)
General disorders
Painful implant site	0/85 (0%)		6/82 (7.3%)
Nervous system disorders
New dizziness	1/85 (1.2%)		0/82 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.