MADIT-CHIC: Multicenter Automatic Defibrillator Implantation Trial - Chemotherapy-Induced Cardiomyopathy
Study Details
Study Description
Brief Summary
The purpose of this trial or study is to determine if cardiac resynchronization therapy (CRT) can be a benefit to people who have impaired heart function due to past treatment with chemotherapy and/or chest radiation. The investigators are looking to enroll approximately 30 eligible subjects with heart failure in this trial. All patients enrolled and registered in the study will be implanted with a cardiac resynchronization therapy device that includes an implantable cardiac defibrillator (CRT-D). Clinical histories, physical exams, and external device testing will be collected both at the time of enrollment in the trial and during follow-up study visits. Following implantation of the CRT-D, patients will be contacted by phone at 3 months and will have a scheduled clinic visit follow-up at 6 months.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
With the advent of new therapies and an increasing number of long-term cancer survivors, the incidence and consequently the interest in chemotherapy-induced cardiomyopathy (CHIC) have been increasing. CHIC is a dose-dependent cardiomyopathy and presents as congestive heart failure several months to years after the administration of chemotherapy and/or chest radiation that includes the heart.
Greater than one-half of the patients exposed to just this class of drugs will show evidence of cardiac dysfunction, with 5% presenting with overt symptomatic heart failure. The overall incidence of CHIC is significantly underestimated as within the US alone, greater than 60,000 patients receive just anthracyclines every year. Despite this, there is little data on their response to conventional heart failure therapy. There is some preliminary evidence from two small, retrospective case-series suggesting that patients with CHIC and evidence of conduction tissue disease (i.e. a wide electrocardiographic depolarization duration (QRS) may significantly benefit from cardiac resynchronization therapy (CRT).
MADIT-CHIC is a multicenter, non-randomized, prospective observational study. The primary aim is to determine if CRT-D (Defibrillator) in high-risk patients with chemotherapy-induced cardiomyopathy will significantly improve left ventricular ejection fraction (LVEF) by echocardiography within 6 months of initiating CRT without adversely affecting mortality.
The study will last 6 months and will be conducted in 10-15 clinical centers in the United States.
Following implantation of the CRT-D device (Defibrillator), patients will be followed for 6 months. The first follow-up contact will be by phone at which time study personnel will review the patient's health status. The last study contact will be a 6-month clinic visit. At the 6-month visit, the patient's health status will be reviewed, the functioning of the CRT-D (Defibrillator) will be tested and an echocardiogram will be conducted. After the 6-month visit, the study-required follow-up will have been completed and patients will continue to have CRT-D (Defibrillator) clinical follow-up based on their physicians direction.
During the course of the study, Subjects will as outlined in the inclusion criteria continue on stable optimal pharmacologic therapy for the cardiac condition that is guideline-based and may include one or more of the following medications: Loop diuretics, Angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blocker (ARB), Aldosterone antagonists and/or Beta-blockers unless the subject is not indicated, contraindicated, or is intolerant of medication.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: CRT-D (Defibrillator) Implantation of a three-lead CRT-D (Defibrillator) in all registered patients |
Device: Three-lead CRT-D (Defibrillator)
The three-lead CRT-D (Defibrillator) will consist of a pulse generator, a right atrial lead, a right ventricular lead and a left ventricular lead.
|
Outcome Measures
Primary Outcome Measures
- Change in Left Ventricular Ejection Fraction [6 months post implant]
The primary endpoint will be the change in left ventricular ejection fraction (LVEF) from baseline to six months
Secondary Outcome Measures
- Number of Participants With All-Cause Mortality [6 months post implant]
Number of Participants with All-Cause Mortality in CRT-D patients
- Effects of CRT Therapy on Left Ventricular Volume at End Diastole [6 months post implant]
Determine based on echocardiogram study if CRT therapy improves left ventricular volume at end diastole (LVEDV) between baseline and six months
- Effects of CRT Therapy on Left Ventricular Volume at End Systole [6 months post implant]
Determine based on echocardiogram study if CRT therapy improves left ventricular volume at end systole (LVESV) between baseline and six months
Other Outcome Measures
- Change in New York Heart Association (NYHA) Functional Class [6 months post implant]
Improvement in NYHA functional class between baseline and six months (yes/no), ie. change from NYHA class III to NYHA II.
- Change in Left Atrial Size [6 months post implant]
Change in left atrial size between baseline and six months
- Effects of CRT on Frequency of Heart Failure [6 months post implant]
Effects of CRT on the frequency of heart failure with end point of inpatient hospitalization with augmented treatment for heart failure
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18 (or of legal age to give informed consent specific to state and national law) up to 80 years of age
-
Male or Female
-
Without clinical heart failure at initiation of chemotherapy/radiation-induced treatment for an underlying malignancy, but developed clinical heart failure (cardiomyopathy: reduced left ventricular ejection fraction (LVEF) with a left bundle branch block (LBBB)-type of conduction disturbance; see next inclusion item) 6 months or more after initiation of the chemotherapy without other evident cause of the cardiomyopathy.
-
Eligible for implantation of a CRT-D (cardiac resynchronization therapy-defibrillator) device according to one of the following options in currently available guidelines:
-
Class 1: Left ventricular ejection fraction (LVEF) less than or equal to 35% AND sinus rhythm AND LBBB (left bundle branch block) with a QRS (electrocardiographic depolarization duration) duration greater than or equal to 150ms AND NYHA (New York Heart Association) class II, III or ambulatory IV symptoms on guideline-directed medical therapy
-
Class 2a1: Left ventricular ejection fraction (LVEF) less than or equal to 35% AND sinus rhythm AND left bundle branch block (LBBB) with a QRS (electrocardiographic depolarization duration) duration 120-149ms AND New York Heart Classification (NYHA) class II, III or ambulatory IV symptoms on guideline-directed medical therapy
-
Class 2a2: Left ventricular ejection fraction (LVEF) less than or equal to 35% AND sinus rhythm AND Non-left bundle branch block (LBBB) with a QRS(electrocardiographic depolarization duration) duration greater than or equal to 150ms AND New York Heart Classification (NYHA) class III or ambulatory IV symptoms on guideline-directed medical therapy
- On stable optimal pharmacologic therapy for the cardiac condition that is guideline-based and may include one or more of the following medications: Loop diuretics, Angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blocker (ARB), Aldosterone antagonists and/or Beta-blockers unless the subject is not indicated, contraindicated, or is intolerant of medication.
Exclusion Criteria:
-
Currently implanted pacemaker or implantable cardioverter defibrillator (ICD) device
-
Previous implant with a CRT (cardiac resynchronization therapy)/CRT-D (cardiac resynchronization therapy-defibrillator) device
-
Cardiac condition not presumed to be caused by chemotherapy
-
Documented symptoms or hemodynamically unstable ventricular tachyarrhythmia
-
On active chemotherapy (must be at least 6 calendar months after last chemotherapy)
-
Permanent or chronic Atrial Fibrillation (AF), or cardioversion for AF within the past 3 calendar months before consent date
-
Structural heart disease such as congenital heart disease, valvular heart disease, e.g., rheumatic valvular heart disease, amyloid heart disease, etc.
-
Coronary artery bypass graft surgery or percutaneous coronary intervention within the past 3 calendar months before consent date
-
Enzyme positive myocardial infarction within the past 3 calendar months prior to consent date
-
Unstable angina requiring hospitalization, with diagnostic work up and intervention within the past 3 months prior to consent date
-
Angiographic evidence of coronary disease who are candidates for coronary revascularization and are likely to undergo coronary artery bypass graft surgery or percutaneous coronary intervention in the foreseeable future
-
Class IV and expected to undergo transplant within study duration
-
Current or past history of drug addiction or abuse that caused cardiomyopathy
-
Pregnant or plans to become pregnant during the course of the trial.
-
Recent cerebral vascular accident or transient ischemia attack within the previous 3 months prior to consent date
-
Presence of any disease, other than the subject's cardiac or cancer disease, associated with a reduced likelihood of survival for the duration of the trial, e.g., uremia, liver failure, active malignant disease, etc.
-
Participating in any other clinical trial
-
Unwilling or unable to cooperate with the protocol
-
Lives at such a distance from the clinic that travel for follow-up visits would be unusually difficult
-
Does not anticipate being a resident of the area for the scheduled duration of the trial
-
Unwilling to sign the consent for participation
-
Physician does not allow participation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCLA Cardiovascular Center | Los Angeles | California | United States | 90095 |
| 2 | MedStar Washington Hospital Center | Washington | District of Columbia | United States | 20010 |
| 3 | University of South Florida | Tampa | Florida | United States | 33606 |
| 4 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 5 | Washington University | Saint Louis | Missouri | United States | 63110 |
| 6 | New York Presbyterian Hospita/Columbia University Medical Center | New York | New York | United States | 10032 |
| 7 | Univeristy of Rochester Medical Center | Rochester | New York | United States | 14642 |
| 8 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
| 9 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- University of Rochester
- Boston Scientific Corporation
Investigators
- Principal Investigator: Valentina Kutyifa, MD, PhD, University of Rochester
Study Documents (Full-Text)
More Information
Publications
None provided.- MADIT-CHIC
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | CRT-D (Defibrillator) |
|---|---|
| Arm/Group Description | Implantation of a three-lead Cardiac Resynchronization Therapy -Defibrillator (CRT-D) in all registered patients Three-lead CRT-D (Defibrillator): The three-lead CRT-D (Defibrillator) will consist of a pulse generator, a right atrial lead, a right ventricular lead and a left ventricular lead. |
| Period Title: Overall Study | |
| STARTED | 30 |
| COMPLETED | 30 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | CRT-D (Defibrillator) |
|---|---|
| Arm/Group Description | Implantation of a three-lead CRT-D (Defibrillator) in all registered patients Three-lead CRT-D (Defibrillator): The three-lead CRT-D (Defibrillator) will consist of a pulse generator, a right atrial lead, a right ventricular lead and a left ventricular lead. |
| Overall Participants | 30 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
14
46.7%
|
| >=65 years |
16
53.3%
|
| Age (years) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [years] |
66
|
| Sex: Female, Male (Count of Participants) | |
| Female |
26
86.7%
|
| Male |
4
13.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
4
13.3%
|
| Not Hispanic or Latino |
22
73.3%
|
| Unknown or Not Reported |
4
13.3%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
7
23.3%
|
| White |
21
70%
|
| More than one race |
1
3.3%
|
| Unknown or Not Reported |
1
3.3%
|
| Region of Enrollment (participants) [Number] | |
| United States |
30
100%
|
| Number of participants with Nonischemic cardiomyopathy (Count of Participants) | |
| Count of Participants [Participants] |
29
96.7%
|
| Median Electrocardiographic depolarization duration (QRS) after consent (ms) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [ms] |
152
|
| Number of participants with Left bundle branch block (LBBB) after consent (Count of Participants) | |
| Count of Participants [Participants] |
30
100%
|
| Sinus rhythm after consent (Count of Participants) | |
| Count of Participants [Participants] |
29
96.7%
|
| Number of participants with Diabetes (Count of Participants) | |
| Count of Participants [Participants] |
6
20%
|
| Number of participants with Hypertension (Count of Participants) | |
| Count of Participants [Participants] |
17
56.7%
|
| Number of participants with a History of ventricular arrhythmias (Count of Participants) | |
| Count of Participants [Participants] |
3
10%
|
| Number of participants with a history of atrial arrhythmias (Count of Participants) | |
| Count of Participants [Participants] |
8
26.7%
|
| Number of participants with Anthracycline history (Count of Participants) | |
| Count of Participants [Participants] |
24
80%
|
| Median Time since cancer diagnosis (years) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [years] |
13.8
|
| Median Age at cancer diagnosis (years) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [years] |
52
|
| Number of participants with History of breast cancer (Count of Participants) | |
| Count of Participants [Participants] |
22
73.3%
|
| Number of participants with a History of leukemia or lymphoma (Count of Participants) | |
| Count of Participants [Participants] |
6
20%
|
| Number of participants with a History of sarcomas (Count of Participants) | |
| Count of Participants [Participants] |
2
6.7%
|
| Median blood urea nitrogen levels (mg/dl) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [mg/dl] |
20
|
| Median Creatinine Levels (mg/dl) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [mg/dl] |
0.95
|
| New York Heart Association class, II (Count of Participants) | |
| Count of Participants [Participants] |
17
56.7%
|
| New York Heart Association class, III (Count of Participants) | |
| Count of Participants [Participants] |
13
43.3%
|
| Median Blood pressure, systolic (mm Hg) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [mm Hg] |
121.5
|
| Median Blood pressure, diastolic (mm Hg) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [mm Hg] |
70.5
|
| Number of participant taking a Beta-Blocker (Count of Participants) | |
| Count of Participants [Participants] |
28
93.3%
|
| Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) (Count of Participants) | |
| Count of Participants [Participants] |
23
76.7%
|
| Number of participants taking a Loop diuretic (Count of Participants) | |
| Count of Participants [Participants] |
28
93.3%
|
| Number of participants taking Aldosterone (Count of Participants) | |
| Count of Participants [Participants] |
15
50%
|
Outcome Measures
| Title | Change in Left Ventricular Ejection Fraction |
|---|---|
| Description | The primary endpoint will be the change in left ventricular ejection fraction (LVEF) from baseline to six months |
| Time Frame | 6 months post implant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Change in left ventricular ejection fraction (LVEF) from baseline to six months was analyzed with 26 patients with data available. |
| Arm/Group Title | CRT-D (Defibrillator) |
|---|---|
| Arm/Group Description | Implantation of a three-lead CRT-D (Defibrillator) in all registered patients |
| Measure Participants | 26 |
| Mean (Standard Deviation) [percentage of LVEF] |
10.6
(6.6)
|
| Title | Number of Participants With All-Cause Mortality |
|---|---|
| Description | Number of Participants with All-Cause Mortality in CRT-D patients |
| Time Frame | 6 months post implant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Event rate of all-cause mortality is described. |
| Arm/Group Title | CRT-D (Defibrillator) |
|---|---|
| Arm/Group Description | Implantation of a three-lead CRT-D (Defibrillator) in all registered patients |
| Measure Participants | 30 |
| Number [participants] |
0
0%
|
| Title | Effects of CRT Therapy on Left Ventricular Volume at End Diastole |
|---|---|
| Description | Determine based on echocardiogram study if CRT therapy improves left ventricular volume at end diastole (LVEDV) between baseline and six months |
| Time Frame | 6 months post implant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Describe 23 patients with data available on LVEDV change |
| Arm/Group Title | CRT-D (Defibrillator) |
|---|---|
| Arm/Group Description | Implantation of a three-lead CRT-D (Defibrillator) in all registered patients |
| Measure Participants | 23 |
| Mean (Standard Deviation) [ml] |
-31.9
(22.5)
|
| Title | Effects of CRT Therapy on Left Ventricular Volume at End Systole |
|---|---|
| Description | Determine based on echocardiogram study if CRT therapy improves left ventricular volume at end systole (LVESV) between baseline and six months |
| Time Frame | 6 months post implant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Describe changes in LVESV in 23 patients with data available |
| Arm/Group Title | CRT-D (Defibrillator) |
|---|---|
| Arm/Group Description | Implantation of a three-lead CRT-D (Defibrillator) in all registered patients Three-lead CRT-D (Defibrillator): The three-lead CRT-D (Defibrillator) will consist of a pulse generator, a right atrial lead, a right ventricular lead and a left ventricular lead. |
| Measure Participants | 23 |
| Mean (Standard Deviation) [ml] |
-37.0
(20.4)
|
| Title | Change in New York Heart Association (NYHA) Functional Class |
|---|---|
| Description | Improvement in NYHA functional class between baseline and six months (yes/no), ie. change from NYHA class III to NYHA II. |
| Time Frame | 6 months post implant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Improvement in NYHA functional class between baseline and six months (yes/no) in 29 participants with data available. |
| Arm/Group Title | CRT-D (Defibrillator) |
|---|---|
| Arm/Group Description | Implantation of a three-lead CRT-D (Defibrillator) in all registered patients |
| Measure Participants | 29 |
| Number [participants] |
12
40%
|
| Title | Change in Left Atrial Size |
|---|---|
| Description | Change in left atrial size between baseline and six months |
| Time Frame | 6 months post implant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Change in left atrial size between baseline and six months was analyzed in 26 patients with data available. |
| Arm/Group Title | CRT-D (Defibrillator) |
|---|---|
| Arm/Group Description | Implantation of a three-lead CRT-D (Defibrillator) in all registered patients |
| Measure Participants | 26 |
| Mean (Standard Deviation) [ml] |
-12.6
(9.6)
|
| Title | Effects of CRT on Frequency of Heart Failure |
|---|---|
| Description | Effects of CRT on the frequency of heart failure with end point of inpatient hospitalization with augmented treatment for heart failure |
| Time Frame | 6 months post implant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Frequency of heart failure described in the study population. |
| Arm/Group Title | CRT-D (Defibrillator) |
|---|---|
| Arm/Group Description | Implantation of a three-lead CRT-D (Defibrillator) in all registered patients |
| Measure Participants | 30 |
| Number [participants] |
1
3.3%
|
Adverse Events
| Time Frame | We have collected data on adverse events during the 6 months follow-up in the study. | |
|---|---|---|
| Adverse Event Reporting Description | The definition of adverse event and/or serious adverse event is the same as on clinicaltrials.gov. | |
| Arm/Group Title | CRT-D (Defibrillator) | |
| Arm/Group Description | Implantation of a three-lead CRT-D (Defibrillator) in all registered patients | |
All Cause Mortality |
||
| CRT-D (Defibrillator) | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/30 (0%) | |
Serious Adverse Events |
||
| CRT-D (Defibrillator) | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/30 (20%) | |
| Cardiac disorders | ||
| Device Infection | 1/30 (3.3%) | 1 |
| Pericardial effusion | 1/30 (3.3%) | 1 |
| Inappropriate device therapy | 1/30 (3.3%) | 1 |
| Heart failure | 1/30 (3.3%) | 1 |
| Infections and infestations | ||
| Parotitis | 1/30 (3.3%) | 1 |
| Nervous system disorders | ||
| Shingles | 1/30 (3.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| CRT-D (Defibrillator) | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/30 (13.3%) | |
| Cardiac disorders | ||
| Hypertension | 2/30 (6.7%) | 2 |
| Atrial fibrillation/flutter | 2/30 (6.7%) | 2 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Valentina Kutyifa MD, PhD |
|---|---|
| Organization | University of Rochester |
| Phone | 585-275-2676 |
| valentina.kutyifa@heart.rochester.edu |
- MADIT-CHIC