Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy

• ClinicalTrials.gov Identifier: NCT01150461
• Recruitment Status: Completed
• First Posted: June 25, 2010
• Results First Posted: September 5, 2013
• Last Update Posted: September 5, 2013
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Michael A. Fifer, MD, Massachusetts General Hospital

Tracking Information

• First Submitted Date: June 22, 2010
• First Posted Date: June 25, 2010
• Results First Submitted Date: May 2, 2013
• Results First Posted Date: September 5, 2013
• Last Update Posted Date: September 5, 2013
• Study Start Date: February 2007
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 3, 2013): Percentage Change From Baseline in Extent of Left Ventricular Fibrosis at 1 Year as Assessed by Magnetic Resonance Imaging. [ Time Frame: Baseline and 1 year ]
• Original Primary Outcome Measures (submitted: June 24, 2010): Extent of left ventricular myocardial fibrosis as assessed by magnetic resonance imaging. [ Time Frame: One Year ]
• Current Secondary Outcome Measures (submitted: September 3, 2013): Percentage Change From Baseline in Left Ventricular Mass at 1 Year as Assessed by Magnetic Resonance Imaging. [ Time Frame: Baseline and 1 year ]
• Original Secondary Outcome Measures (submitted: June 24, 2010): Left ventricular mass as assessed by magnetic resonance imaging. [ Time Frame: 1 year ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy
• Official Title: Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy
• Brief Summary: The purpose of this study is to determine whether taking losartan helps people with hypertrophic nonobstructive cardiomyopathy feel better by decreasing the amount of heart muscle thickening and/or the amount of heart muscle scarring.

Detailed Description

Hypertrophic cardiomyopathy (HCM) is characterized by idiopathic cardiac hypertrophy, heart failure, ischemia even in the absence of epicardial coronary artery disease, and arrhythmias. The pathological features of HCM include hypertrophy and disarray, interstitial fibrosis, and increased arteriolar wall thickness. Hypertrophy and fibrosis are major determinants of morbidity and mortality in hypertrophic cardiomyopathy. Some investigators have demonstrated that interstitial fibrosis and hypertrophy occur secondarily, in response to trophic and mitotic factors in the heart. Therefore, blocking trophic factors may attenuate or potentially reverse hypertrophy and fibrosis in HCM.

Angiotensin II has trophic and profibrotic effects on the heart, and blockade of angiotensin II type I receptors has been shown to attenuate myocardial hypertrophy and fibrosis in acquired cardiac disease in humans and animal models.

We hypothesize that treatment with the selective angiotensin II type receptor antagonist, losartan, will decrease both hypertrophy and fibrosis, improve diastolic function, reduce symptoms, and improve functional status in patients with HCM.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Hypertrophic Cardiomyopathy

Intervention

• Drug: losartan
  Losartan 50 mg b.i.d
  Other Names:

  • Angiotensin II receptor antagonist
  • Cozaar
• Drug: placebo
  Placebo b.i.d.
  Other Name: Placebo tablet

Study Arms

• Experimental: losartan
  Losartan 50 mg b.i.d.
  Intervention: Drug: losartan
• Placebo Comparator: placebo
  Placebo b.i.d.
  Intervention: Drug: placebo

• Publications *: Shimada YJ, Passeri JJ, Baggish AL, O'Callaghan C, Lowry PA, Yannekis G, Abbara S, Ghoshhajra BB, Rothman RD, Ho CY, Januzzi JL, Seidman CE, Fifer MA. Effects of losartan on left ventricular hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy. JACC Heart Fail. 2013 Dec;1(6):480-7. doi: 10.1016/j.jchf.2013.09.001. Epub 2013 Oct 24.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 3, 2013): 20
• Original Estimated Enrollment (submitted: June 24, 2010): 24
• Actual Study Completion Date: July 2010
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with hypertrophic cardiomyopathy
• Left ventricular outflow tract (LVOT) gradient less than 30 mm Hg at rest
• Age 18 years or older

Exclusion Criteria:

• Contraindication to losartan
• Already taking losartan
• Contraindication to MRI
• Hemodynamic instability

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01150461
• Other Study ID Numbers: 2006P002232/7
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Michael A. Fifer, MD, Massachusetts General Hospital
• Study Sponsor: Massachusetts General Hospital
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michael A Fifer, MD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: September 2013