PRECEDE-HF: Evaluation of Cardiac Compass With OptiVol in the Early Detection of Decompensation Events for Heart Failure

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00510198
• Collaborator: (none)
• Enrollment: 120
• Locations: 33
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the PRECEDE-HF study is to collect data to compare patients whose heart failure is managed using Cardiac Compass with OptiVol (which is a tool in the device that records information about the heart that doctors can use to help treat their heart disease) combined with standard treatment methods (Access Group) to patients whose heart failure is managed by standard treatment methods only (Control Group). This comparison will show if the additional monitoring provided by Cardiac Compass with OptiVol delays the time patients are first admitted to hospital for heart failure or delays the time to death.

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure	Device: Cardiac Compass with OptiVol Fluid Status Monitoring; Device: Standard of Care alone (clinical assessment)	N/A

Detailed Description

PRECEDE-HF was a prospective, multi-center, randomized, investigational device exemption (IDE) clinical study. The purpose of this study was to collect data required to determine whether the use of Cardiac Compass including OptiVol Fluid Status Monitoring with standard clinical assessment ("Access Arm") will result in a longer time to first heart failure hospitalization or death compared to standard clinical assessment alone ("Control Arm") and to support the approval of the following device features:

• OptiVol Alert (audible and home monitor alerts) for use in Medtronic devices

• SentryCheck™ Monitor

• OptiVol Alert Suspend (OptiVol enhancement)

• OptiVol Reference Impedance Adjustment (OptiVol enhancement)

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: PRECEDE-HF -Prospective, Randomized Evaluation of Cardiac Compass With OptiVol in the Early Detection of Decompensation Events for Heart Failure
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control Arm 1: SOC and CC with OptiVol Standard of Care and Cardiac Compass with OptiVol as the Control. Intervention is standard of care, such as symptom assessment with the addition of viewing Cardiac Compass trends and the OptiVol diagnostic.	Device: Cardiac Compass with OptiVol Fluid Status Monitoring; Review of Cardiac Compass with OptiVol Fluid Status Monitoring
Active Comparator: Control Arm 2: SOC Intervention is Standard of Care alone, such as assessment of symptoms, only. Device trending information, but OptiVol is not allowed.	Device: Standard of Care alone (clinical assessment); Clinical assessment utilizing standard of care, alone.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Heart-Failure Hospitalization or All-Cause Death [Up to five years]

   A composite endpoint of heart-failure hospitalization or all-cause death. To demonstrate a longer time to first heart failure (HF) hospitalization or death in HF subjects managed with standard clinical assessment using Cardiac Compass Trends with OptiVol Fluid Status Monitoring ("Access Arm") compared to HF subjects managed with standard clinical assessment alone ("Control Arm")

2. Number of Subjects Proportion Who Have a Safety Composite Event Within the First 6 Months Post-randomization Between the Access Arm and the Control Arm [Up to five years]

   A safety composite event is defined as an event that includes one or more of the following: Syncope, Worsening renal function resulting in IV therapy, ultrafiltration, or dialysis, Hypotension and/or hypovolemia resulting in the administration of IV fluids, Clinically significant electrolyte abnormalities resulting in IV replacement or ER/hospitalization for correction, Appropriately detected sustained VT/VF episode, Death

Secondary Outcome Measures

1. Combined Endpoint of All-cause Mortality and Cardiovascular Hospitalizations [up to five years]

   To demonstrate a reduction in the combined endpoint of all-cause mortality and cardiovascular hospitalizations in the Access Arm compared to the Control Arm

2. Cardiovascular Hospitalizations [up to five years]

   To demonstrate a reduction in cardiovascular hospitalizations in the Access Arm compared to the Control Arm

Eligibility Criteria

Criteria

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

Inclusion Criteria

The following criteria apply to all subjects:

• Subject has a CRT-D or dual chamber ICD with Cardiac Compass and OptiVol Fluid Status Monitoring implanted in the pectoral region at least 30 days prior to enrollment. CRT-D/ICD must be supported by the Medtronic CareLink Network.

• Subject has a market-released, transvenous, high voltage RV lead

• Subject has a market-released RA lead

• If subject has an LV lead, it must be compatible, not Y-adapted and not currently under investigation

• Subject's heart failure regimen (i.e. beta blocker and ACE inhibitor (or substitute) unless documented evidence of intolerance is available) adheres to current ACC/AHA guidelines for management of chronic heart failure in adult patients

• Subject has a history of at least one heart failure related hospitalization, Emergency Department (ED) visit, or urgent visit necessitating IV diuretic, IV inotropic, IV vasodilator, or other parenteral therapy within 12 months prior to baseline evaluation

• Subject is at least 18 years of age

• Subject is willing and able to comply with the Clinical Investigation Plan (e.g. willing and able to remain available for follow-up visits, use SentryCheck, etc.)

• Subject is willing and able to transmit data using the Medtronic CareLink Network

• Subject (or subject's legally authorized representative) is willing and able to sign and date the study Informed Consent and HIPAA Authorization (U.S.)

Exclusion Criteria

The following criteria apply to all subjects:

• Subject is post heart transplant or actively listed on the transplant list and reasonable probability (as defined by investigator) of undergoing transplantation in the next year

• Subject received a coronary artery bypass graft or valve surgery in the last 90 days

• Subject had a myocardial infarction (MI) in the last 90 days.

• Subject is indicated for valve replacement/repair

• Subject's life expectancy due to non-cardiac reasons is less than six months

• Subject has serum creatinine > 2.5 mg/dL measured within 30 days prior to enrollment.

• Subject is on chronic renal dialysis

• Subject is on continuous or intermittent (> 2 stable infusions per week) infusion therapy for HF

• Subject has complex and uncorrected congenital heart disease

• Subject is enrolled in a Disease Management Program where an outside vendor, company or service is employed to determine, monitor, and/ or alert a clinician or subject to weight changes or other HF signs or symptoms via interactive or passive systems

• Subject is implanted with a cardiac hemodynamic monitor or left ventricular assist device(LVAD)

• Subject is enrolled in a concurrent study, with the exception of a study approved by the Medtronic PRECEDE-HF Clinical Trial Leader prior to enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Anchorage	Alaska	United States	99508
2		Little Rock	Arkansas	United States	72205
3		Berkeley	California	United States	94705
4		Larkspur	California	United States	94939
5		Colorado Springs	Colorado	United States	80909
6		Fort Collins	Colorado	United States	80528
7		Jacksonville	Florida	United States	32207
8		Atlanta	Georgia	United States	30306
9		Kankakee	Illinois	United States	60901
10		Oak Lawn	Illinois	United States	60453
11		Rockford	Illinois	United States	61107
12		Indianapolis	Indiana	United States	46260
13		Louisville	Kentucky	United States	40205
14		New Orleans	Louisiana	United States	70121
15		Takoma Park	Maryland	United States	20912
16		Springfield	Massachusetts	United States	01199
17		Saginaw	Michigan	United States	48601
18		Ypsilanti	Michigan	United States	48197
19		Saint Cloud	Minnesota	United States	56303
20		Saint Joseph	Missouri	United States	64501
21		Saint Louis	Missouri	United States	63110
22		Albany	New York	United States	12212
23		Akron	Ohio	United States	44304
24		Cleveland	Ohio	United States	44195
25		Columbus	Ohio	United States	43210
26		Elyria	Ohio	United States	44035
27		Oklahoma City	Oklahoma	United States	73120
28		Doylestown	Pennsylvania	United States	18901
29		Lancaster	Pennsylvania	United States	17603
30		Nashville	Tennessee	United States	37205
31		Austin	Texas	United States	78705
32		Richmond	Virginia	United States	23294
33		Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• Medtronic Cardiac Rhythm and Heart Failure

Investigators

• Study Chair: PRECEDE-HF Study Team, Medtronic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medtronic Cardiac Rhythm and Heart Failure
• ClinicalTrials.gov Identifier: NCT00510198
• Other Study ID Numbers: 603
• First Posted: Aug 1, 2007
• Last Update Posted: Apr 10, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Medtronic Cardiac Rhythm and Heart Failure: Heart Disease; Congestive Heart Failure; Thoracic Fluid Monitoring
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Pre-assignment Detail	120 subjects were enrolled but 3 were not randomized into the study for not meeting the inclusion/exclusion criteria.

Arm/Group Title	Access Arm	Control Arm
Arm/Group Description	Standard of Care and Cardiac Compass with OptiVol	Standard of Care alone
Period Title: Overall Study
STARTED	59	58
COMPLETED	54	54
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	Access Arm	Control Arm	Total
Arm/Group Description	Standard of Care and Cardiac Compass with OptiVol	Standard of Care alone	Total of all reporting groups
Overall Participants	59	58	117
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 35.6%	23 39.7%	44 37.6%
>=65 years	38 64.4%	35 60.3%	73 62.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.5 (17.3)	63.8 (15.1)	64.7 (16.2)
Sex: Female, Male (Count of Participants)
Female	13 22%	23 39.7%	36 30.8%
Male	46 78%	35 60.3%	81 69.2%
Region of Enrollment (participants) [Number]
United States	59 100%	58 100%	117 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Heart-Failure Hospitalization or All-Cause Death
Description	A composite endpoint of heart-failure hospitalization or all-cause death. To demonstrate a longer time to first heart failure (HF) hospitalization or death in HF subjects managed with standard clinical assessment using Cardiac Compass Trends with OptiVol Fluid Status Monitoring ("Access Arm") compared to HF subjects managed with standard clinical assessment alone ("Control Arm")
Time Frame	Up to five years

Outcome Measure Data

Analysis Population Description

all randomized subjects; intention to treat

Arm/Group Title	Access Arm	Control Arm
Arm/Group Description	Standard of Care and Cardiac Compass with OptiVol	Standard of Care alone
Measure Participants	59	58
Number [Participants with an Event]	14 23.7%	9 15.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Access Arm, Control Arm
	Comments	This is a log-rank test, which uses the time from randomization to first composite endpoint event to compare the risk of event between Access and Control arms.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments	The log-rank test was conducted at an alpha level of 0.05. The study was terminated early due to enrollment significantly below protocol expectation. Due to the low sample size and consequently low statistical power, no conclusion can be drawn.
	Method	Log Rank
	Comments

2. Primary Outcome

Title	Number of Subjects Proportion Who Have a Safety Composite Event Within the First 6 Months Post-randomization Between the Access Arm and the Control Arm
Description	A safety composite event is defined as an event that includes one or more of the following: Syncope, Worsening renal function resulting in IV therapy, ultrafiltration, or dialysis, Hypotension and/or hypovolemia resulting in the administration of IV fluids, Clinically significant electrolyte abnormalities resulting in IV replacement or ER/hospitalization for correction, Appropriately detected sustained VT/VF episode, Death
Time Frame	Up to five years

Outcome Measure Data

Analysis Population Description

all randomized subjects; intention to treat

Arm/Group Title	Access Arm	Control Arm
Arm/Group Description	Standard of Care and Cardiac Compass with OptiVol	Standard of Care alone
Measure Participants	59	58
Number [Number of Participants with a Event]	16 27.1%	13 22.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Access Arm, Control Arm
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Pre-specified non-inferiority margin was 7.5%
Statistical Test of Hypothesis	p-Value	0.36
	Comments	The study was terminated early due to enrollment significantly below protocol expectation. Due to the low sample size and consequently low statistical power, no conclusion can be drawn.
	Method	Two-sample test of proportions
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	4.7
	Confidence Interval	(2-Sided) 95%; -10.9 to 20.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	The risk difference estimate is the difference between the Access Arm and Control arm.

3. Secondary Outcome

Title	Combined Endpoint of All-cause Mortality and Cardiovascular Hospitalizations
Description	To demonstrate a reduction in the combined endpoint of all-cause mortality and cardiovascular hospitalizations in the Access Arm compared to the Control Arm
Time Frame	up to five years

Outcome Measure Data

Analysis Population Description

Study was stopped early, therefore secondary objectives were not analyzed.

Arm/Group Title	Access Arm: Standard of Care and Cardiac Compass With OptiVol	Control Arm: Standard of Care Alone
Arm/Group Description	Standard of Care and Cardiac Compass with OptiVol Cardiac Compass with OptiVol Fluid Status Monitoring: Review of Cardiac Compass with OptiVol Fluid Status Monitoring	Standard of Care alone Standard of Care alone (clinical assessment): Clinical assessment utilizing standard of care, alone.
Measure Participants	0	0

4. Secondary Outcome

Title	Cardiovascular Hospitalizations
Description	To demonstrate a reduction in cardiovascular hospitalizations in the Access Arm compared to the Control Arm
Time Frame	up to five years

Outcome Measure Data

Analysis Population Description

The study was stopped early, therefore secondary objectives were not able to be analyzed.

Arm/Group Title	Access Arm: Standard of Care and Cardiac Compass With OptiVol	Control Arm: Standard of Care Alone
Arm/Group Description	Standard of Care and Cardiac Compass with OptiVol Cardiac Compass with OptiVol Fluid Status Monitoring: Review of Cardiac Compass with OptiVol Fluid Status Monitoring	Standard of Care alone Standard of Care alone (clinical assessment): Clinical assessment utilizing standard of care, alone.
Measure Participants	0	0

Adverse Events

Time Frame	up to five years
Adverse Event Reporting Description	Definition of Serious AE: Any significant adverse experience, including those which may be either life threatening or involve permanent or long term injuries, but excluding injuries that are non-life threatening and that are temporary and reasonably reversible.
Arm/Group Title	Access Arm		Control Arm
Arm/Group Description	Standard of Care and Cardiac Compass with OptiVol		Standard of Care alone
All Cause Mortality
	Access Arm		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Access Arm		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/59 (54.2%)		21/58 (36.2%)
Blood and lymphatic system disorders
ANEMIA	0/59 (0%)	0	1/58 (1.7%)	1
Cardiac disorders
ATRIAL FLUTTER	1/59 (1.7%)	1	2/58 (3.4%)	2
ACUTE DECOMPENSATED HEART FAILURE	17/59 (28.8%)	40	11/58 (19%)	31
ANGINA PECTORIS	2/59 (3.4%)	2	1/58 (1.7%)	1
ATRIAL FIBRILLATION	1/59 (1.7%)	1	2/58 (3.4%)	2
BRADYCARDIA	0/59 (0%)	0	1/58 (1.7%)	1
CHEST PAIN	1/59 (1.7%)	1	0/58 (0%)	0
DYSPNEA	1/59 (1.7%)	1	1/58 (1.7%)	1
EDEMATOUS WEIGHT GAIN	1/59 (1.7%)	1	0/58 (0%)	0
HYPOTENSION	1/59 (1.7%)	1	1/58 (1.7%)	1
ISCHEMIC HEART DISEASE	0/59 (0%)	0	1/58 (1.7%)	1
NEAR SYNCOPE	1/59 (1.7%)	1	0/58 (0%)	0
SYNCOPE	1/59 (1.7%)	1	1/58 (1.7%)	1
VENTRICULAR TACHYCARDIA	3/59 (5.1%)	3	2/58 (3.4%)	2
Endocrine disorders
FOOT ULCER	0/59 (0%)	0	1/58 (1.7%)	1
THYROID MASS	0/59 (0%)	0	1/58 (1.7%)	1
Eye disorders
CATARACT	1/59 (1.7%)	1	0/58 (0%)	0
Gastrointestinal disorders
ABDOMINAL PAIN	1/59 (1.7%)	1	1/58 (1.7%)	1
FOREIGN BODY IN GI TRACT	1/59 (1.7%)	1	0/58 (0%)	0
GASTRITIS	1/59 (1.7%)	1	0/58 (0%)	0
GASTROENTERITIS	1/59 (1.7%)	1	0/58 (0%)	0
GERD	1/59 (1.7%)	1	0/58 (0%)	0
GI BLEED	0/59 (0%)	0	1/58 (1.7%)	1
PARALYTIC ILEUS	1/59 (1.7%)	1	0/58 (0%)	0
RECTAL PROLAPSE	1/59 (1.7%)	1	0/58 (0%)	0
General disorders
ASCITES	1/59 (1.7%)	1	0/58 (0%)	0
CHEST PAIN (NON-CARDIAC)	0/59 (0%)	0	1/58 (1.7%)	1
Hepatobiliary disorders
CHOLECYSTECTOMY	0/59 (0%)	0	1/58 (1.7%)	1
CHOLELITHIASIS	0/59 (0%)	0	1/58 (1.7%)	1
CIRROHSIS	0/59 (0%)	0	1/58 (1.7%)	1
Immune system disorders
GOUT	1/59 (1.7%)	1	0/58 (0%)	0
Infections and infestations
CENTRAL LINE INFECTION	1/59 (1.7%)	1	1/58 (1.7%)	1
IMPLANT SITE INFECTION	1/59 (1.7%)	1	0/58 (0%)	0
SEPSIS	0/59 (0%)	0	2/58 (3.4%)	2
Injury, poisoning and procedural complications
DIGOXIN TOXICITY	1/59 (1.7%)	1	1/58 (1.7%)	1
DRUG INTOLERANCE	0/59 (0%)	0	1/58 (1.7%)	1
INJURY TO HAND NOS	0/59 (0%)	0	1/58 (1.7%)	1
LEAD CONDUCTOR FRACTURE	1/59 (1.7%)	1	0/58 (0%)	0
OVERSENSING	1/59 (1.7%)	1	0/58 (0%)	0
Metabolism and nutrition disorders
DEHYDRATION	0/59 (0%)	0	1/58 (1.7%)	1
Musculoskeletal and connective tissue disorders
BACK PAIN	0/59 (0%)	0	1/58 (1.7%)	1
LUMBAR VERTEBRAL FRACTURE L1	0/59 (0%)	0	1/58 (1.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER	0/59 (0%)	0	1/58 (1.7%)	1
Renal and urinary disorders
PYELONEPHRITIS	0/59 (0%)	0	1/58 (1.7%)	1
RENAL FAILURE	4/59 (6.8%)	4	4/58 (6.9%)	4
RENAL INSUFFICIENCY	0/59 (0%)	0	1/58 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
BRONCHITIS	1/59 (1.7%)	1	0/58 (0%)	0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	2/59 (3.4%)	2	0/58 (0%)	0
PNEUMONIA	3/59 (5.1%)	3	1/58 (1.7%)	1
Vascular disorders
CAROTID ARTERY STENOSIS	1/59 (1.7%)	1	0/58 (0%)	0
Other (Not Including Serious) Adverse Events
	Access Arm		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/59 (18.6%)		3/58 (5.2%)
Cardiac disorders
ACUTE DECOMPENSATED HEART FAILURE	4/59 (6.8%)	4	0/58 (0%)	0
Immune system disorders
GOUT	4/59 (6.8%)	6	2/58 (3.4%)	2
Psychiatric disorders
ANXIETY	3/59 (5.1%)	3	1/58 (1.7%)	1

Limitations/Caveats

Because none of primary objectives of the study have been met, the pre-specified analyses for all secondary objectives were not performed (per study protocol).

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.