Clinical trial NCT01872234: MADIT ASIA Cardiac Resynchronization Trial
Official title: MADIT ASIA Cardiac Resynchronization Trial (MADIT-ASIA)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Congestive Heart Failure
Left Bundle Branch Block
Heart Failure, Systolic
Keywords: Heart Failure
Cardiac Resynchronization Therapy
Mild systolic dysfunction
Left Bundle Branch Block
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
Collaborators: name: University of Rochester
First posted: 2013-06-07
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial or study is to determine if pacemaker therapy can be a beneficial alternative to conventional medical therapy in patients with a history of moderate heart failure. The investigators are looking to enroll approximately 180 people in this trial. Patients will be randomized in two groups. One group will be implanted with a pacemaker and will continue to receive conventional medical therapy as prescribed by their doctor. The second group will continue to receive conventional medical therapy as prescribed by their doctor and will not be implanted with a pacemaker. 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. Patients who enter the study will be seen for study visits at 1 month, 3 and 6 months.

Detailed description: MADIT-ASIA is a multicenter, prospective, randomized clinical study. The primary aim is to show that two lead CRT-P with guideline-based optimal pharmacological therapy is associated with a significantly greater improvement in left ventricular ejection fraction (LVEF) at 6 months compared with guideline-based optimal pharmacologic therapy only.

The study will be initially conducted at approximately 25 centers in up to 9 countries in Asia including India, Thailand, Taiwan, Malaysia, China, Japan, South Korea and Singapore. If necessary, more sites may be invited to participate to meet the enrollment goal.

Following randomization, subjects will have scheduled clinic visit follow-ups at 1, 3 and 6-month intervals. Relevant event history, cardiac medications, physical assessment, device interrogation/programming status and adverse events will be collected at each follow-up visit. At the 6-month visit, a repeat echocardiogram and a 12-lead ECG will be obtained. Subjects will be followed through the 6 month visit. After that, subjects will have a safety follow up contact at the end of the study. The study will end when the last randomized subject reaches the 6 months visit.

Eligibility criteria: Inclusion Criteria:

* Subject is age 18 or above, or of legal age to give informed consent specific to state and national law
* Hospitalization for heart failure using the Framingham criteria requiring medical treatment more than 4 weeks ago but less than six months prior to randomization date
* Subject in sinus rhythm
* Subject with QRS duration \>110 milliseconds and left bundle branch block or incomplete left bundle branch block
* Subject with ejection fraction 36-50%
* Subject with ischemic or non-ischemic heart disease
* Subject 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 (e.g., furosemide, bumetanide, torsemide) unless the subject is not indicated, is contraindicated, or is intolerant of loop diuretics; Angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blocker (ARB) unless the subject failed, is not indicated, or is contraindicated for these therapies; Aldosterone antagonists unless the subject is not indicated, or is intolerant of aldosterone antagonists; Beta-blockers unless the subject is not indicated, contraindicated, or is intolerant of beta-blockers. The choice of selective or non-selective beta-blockers use is left to the Investigator's discretion \* For purposes of the study, "stable" is defined as beta blockers and ACE/ARB for at least three months prior to randomization, unless contraindicated or not tolerated, with stable doses for at least one month prior to randomization. It is permissible for diuretic and aldosterone antagonist dosage to have been adjusted as necessary.

Exclusion Criteria:

* Subject with a currently implanted pacemaker, ICD, CRT-P or CRT-D generator or device component
* Subject with a history of spontaneous sustained VT\>160 bpm or VF
* Subject with permanent or chronic AF, or cardioversion for AF within the past 3 calendar months before randomization
* Subject with structural heart disease such as congenital heart disease, valvular heart disease, e.g., rheumatic valvular heart disease, amyloid heart disease, etc.
* Subject with coronary artery bypass graft surgery or percutaneous coronary intervention within the past 3 calendar months before randomization
* Subject with enzyme positive myocardial infarction within the past 3 calendar months prior to randomization
* Subject with 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
* Right bundle branch block or non-specific interventricular conduction delay
* Subject with second or third degree heart block
* Subject in New York Heart Association Class IV (symptoms of heart failure at rest)
* Subject who is pregnant or plans to become pregnant during the course of the trial. Note: Women of childbearing potential must have a negative pregnancy test within 7 days prior to randomization
* Subject with irreversible brain damage from pre-existing cerebral disease
* Subject with presence of any disease, other than the subject's cardiac disease, associated with a reduced likelihood of survival for the duration of the trial, e.g., cancer, uremia, liver failure, etc.
* Subject with chronic renal disease with blood urea nitrogen (BUN) \> 50mg/dl (18 mmol/l) or creatinine \> 2.5mg/dl (221 µmol/l)
* Subject participating in any other clinical trial
* Subject unwilling or unable to cooperate with the protocol
* Subject who lives at such a distance from the clinic that travel for follow-up visits would be unusually difficult
* Subject who does not anticipate being a resident of the area for the scheduled duration of the trial
* Subject unwilling to sign the consent for participation
* Subject whose physician does not allow participation

Primary outcomes:
measure: Primary Endpoint
timeFrame: 6 months post randomization
Secondary outcomes:
measure: All-cause mortality
timeFrame: 6 months post randomization
measure: Recurrent heart failure or cardiovascular death, whichever comes first
timeFrame: 6 months post randomization
measure: Changes in Left Ventricular End Systolic Volume (LVESV) and in Left Ventricular End Diastolic Volume (LVEDV)
timeFrame: 6 months post randomization
measure: Change in NYHA functional class
timeFrame: 6 months post randomization
measure: Atrial fibrillation events
timeFrame: 6 months post randomization
measure: Change in left atrial size
timeFrame: 6 months post randomization
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Grantham Hospital
state: Hong Kong
city: Hong Kong
country: China
facility: Queen Mary Hospital
state: Hong Kong
city: Shatin
country: China
facility: Prince of Wales Hospital
state: Hong Kong
city: Beijing
country: China
facility: Fu Wai Hospital
city: Hangzhou
country: China
facility: Zhejiang hospital Hangzhou
city: Shanghai
country: China
facility: Zhongshan hospital Shanghai
city: Gurgaon
country: India
facility: Medanta-Medicity
state: Haryana
city: Hyderabad
country: India
facility: CARE Hospital Nampally, Hyderabad
city: New Delhi
country: India
facility: Fortis Escorts Health Institute, New Delhi
city: Shinjuku
country: Japan
facility: Tokyo Women's Medical Univesity Hospital
state: Tokyo
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul ASAN Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Medical Center - Severance Hospital
city: Kuala Lumpur
country: Malaysia
facility: Institut Jantung Negara
city: Singapore
country: Singapore
facility: National Heart Center
city: Singapore
country: Singapore
facility: National University Heart Center Singapore
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Linkou
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Bangkok
country: Thailand
facility: Her Majesty's Cardiac Center, Siriraj Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital, Mahidol University
Study officials:
affiliation: Univ. of Rochester Medical Center, Rochester, New York 14642, heartajm@heart.rochester.edu
name: Arthur J. Moss, M.D.
role: PRINCIPAL_INVESTIGATOR
References: