Early Percutaneous Mitral Intervention in Asymptomatic Moderate Mitral Stenosis (MITIGATE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Asan Medical Center
Sponsor:
Information provided by (Responsible Party):
Duk-Hyun Kang, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01406353
First received: July 28, 2011
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

Although percutaneous mitral commissurotomy (PMC) has been accepted as an effective treatment for symptomatic patients with moderate or severe mitral stenosis (MS), most asymptomatic patients are not candidates for PMC owing to the small but inherent procedure-related risks. Asymptomatic patients with MS show good survival rates up to 10 years, but there was a sudden deterioration precipitated by atrial fibrillation or embolism in half of the patients. Because the success rates of PMC were improved to more than 95% in ideal patients from highly selected centers and early PMC may decrease the occurrence of adverse events, such as atrial fibrillation or embolism, experienced centers tend to perform PMC at an early stage of disease. However, the potential benefits of early preemptive PMC in asymptomatic patients should be balanced against the real risks related to the procedure, and further studies of the efficacy of PMC in the prevention of embolism are necessary to extend its indications to asymptomatic patients. To the best of our knowledge, No randomized trials have been performed to ascertain the optimal timing of intervention in asymptomatic patients with significant MS. The early percutaneous MITral Intervention versus conventional manaGement in Asymptomatic moderate miTral stEnosis (MITIGATE) trial was designed to compare clinical outcomes of early intervention with those of a conventional management based on current guidelines in asymptomatic moderate mitral stenosis.


Condition Intervention Phase
Moderate Mitral Stenosis
Procedure: Percutaneous Mitral Commissurotomy
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Early Percutaneous Mitral Intervention Versus Conventional Management in Asymptomatic Moderate Mitral Stenosis

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Composite of cardiovascular event [ Time Frame: Participants will be followed for the duration of the trial, an expected average of 3 years ] [ Designated as safety issue: Yes ]
    Composite of cardiovascular mortality, cerebral infarction, systemic embolic events that occurred during follow-up, and PMC-related complications; procedural mortality and urgent MV surgery.


Secondary Outcome Measures:
  • all-cause death and each component of cardiovascular event [ Time Frame: Participants will be followed for the duration of the trial, an expected average of 3 years ] [ Designated as safety issue: Yes ]
    all-cause death and any component of composite primary end point.


Estimated Enrollment: 166
Study Start Date: July 2011
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Early Percutaneous Mitral Intervention
early elective percutaneous mitral commissurotomy within 3 months of enrollment
Procedure: Percutaneous Mitral Commissurotomy
Percutaneous mitral commissurotomy is performed by experienced interventional cardiologists using the Inoue balloon technique. During the procedure, conventional hemodynamic parameters are monitored. A successful immediate result is defined as a mitral valve area > 1.5 square cm with less than moderate to severe mitral regurgitation.
Other Name: Percutaneous mitral valvuloplasty
No Intervention: Conventional Treatment
All patients in the conventional treatment group regularly visit their attending physicians at 3 monthly interval for maintenance of anticoagulation therapy or every year for annual re-evaluation. Patients who become symptomatic during follow-up are referred for percutaneous mitral commissurotomy or mitral valve surgery.

Detailed Description:

We enroll consecutive asymptomatic patients with moderate mitral stenosis who are candidates for both early percutaneous mitral commissurotomy (PMC) and conventional treatment at 3 centers in Seoul, Korea.

Echocardiographic evaluation is performed before enrollment, immediately after PMC and annually during follow-up. All patients undergo two-dimensional echocardiography and/or transesophageal echocardiography to detect left atrial thrombi. Morphologic features of the mitral valve (MV) are categorized as described previously (14), and total echocardiographic score is obtained by adding the scores for leaflet mobility, thickness, calcification, and subvalvular lesions. The MVA is measured by direct planimetry of the mitral orifice, and MS severity is graded as mild, moderate, or severe when MVA was > 1.5, 1.0 to 1.5, or < 1.0 cm2, respectively. The severity of mitral and tricuspid regurgitation is assessed semiquantitatively or using quantitative methods and classified as mild, moderate, or severe. Pulmonary artery systolic pressure (PAP) is estimated by continuous wave Doppler with the simplified Bernoulli equation.

All study patients regularly visit their attending physicians at 3 monthly interval for maintenance of anticoagulation therapy or every year for annual re-evaluation. Patients in the conventional treatment group who become symptomatic during follow-up are referred for PMC or mitral valve surgery. An embolic event is defined as a systemic embolism fulfilling both prespecified criteria: acute onset of clinical symptoms or signs of embolism and occurrence of new lesions confirmed by imaging studies. A specific diagnosis of cerebral infarction is confirmed by an experienced neurologist and additional brain magnetic resonance imaging is performed if indicated.

We estimate that a sample size of 166 patients would provide 80% power to detect a significant difference with respect to the primary end point at the 2-sided significance level of 0.05, assuming 3-year event rates of 13% in the conventional treatment group and 2% in the early PMC group, and drop-out rate of 5%. These rates are based on the results of our previous study. Analyses are performed on an intention-to-treat basis. To analyze primary outcome, estimates of cumulative event rates are calculated by the Kaplan-Meier method and compared employing the log-rank test. For Kaplan-Meier analysis, we analyze all clinical events by time to first event. Hazard ratios with 95% confidence intervals are derived with the use of the Cox proportional hazards model.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • asymptomatic patients with moderate MS who are potential candidates for early percutaneous mitral commissurotomy

Exclusion Criteria:

  • patients with exertional dyspnea
  • total echocardiographic score > 10
  • moderate to severe mitral regurgitation
  • left atrial thrombi
  • significant aortic valve disease,
  • left ventricle (LV) ejection fraction (EF) <50%
  • Doppler-estimated pulmonary artery systolic pressure >50 mmHg
  • those who were not candidates for early intervention based on age > 70 years or the presence of coexisting malignancies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01406353

Contacts
Contact: Duk-Hyun Kang, MD, PhD 82-2-3010-3166 ext No dhkang@amc.seoul.kr
Contact: Byung Joo Sun, MD 82-2-3010-1540 ext No lionheart@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Byung Joo Sun, MD    82-2-3010-1540 ext No    lionheart@amc.seoul.kr   
Principal Investigator: Duk-Hyun Kang, MD, PhD         
Sub-Investigator: Byung Joo Sun, MD         
Samsung Medical Center Not yet recruiting
Seoul, Korea, Republic of
Contact: Seung Woo Park, MD, PhD       parksmc@gmail.com   
Principal Investigator: Seung Woo Park, MD, PhD         
Yonsei University Severance Hospital Not yet recruiting
Seoul, Korea, Republic of
Contact: Myeong-Ki Hong, MD, PhD       mkhong61@yuhs.ac   
Principal Investigator: Myeong-Ki Hong, MD, PhD         
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Duk-Hyun Kang, MD, PhD Asan Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Duk-Hyun Kang, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01406353     History of Changes
Other Study ID Numbers: 2011-0432
Study First Received: July 28, 2011
Last Updated: May 20, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Asan Medical Center:
Mitral Stenosis
Mitral Valvuloplasty

Additional relevant MeSH terms:
Constriction, Pathologic
Mitral Valve Stenosis
Cardiovascular Diseases
Heart Diseases
Heart Valve Diseases
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on October 30, 2014