Pharmacological Reduction of Functional, Ischemic Mitral REgurgitation

NCT02687932 | Completed Phase 4 DMC

• 1 other identifier: 2015-0938
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 4

Brief Summary

Functional MR is caused by adverse left ventricular remodeling after myocardial injury and associated with an increased incidence of heart failure and death. Because secondary functional MR usually develops as a result of LV dysfunction, diuretics, beta blockers, angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB), and aldosterone antagonists are given to patients with functional MR in line with the guidelines in the management of heart failure. However, functional MR appears to remain common despite use of these drugs and current medical treatment is usually insufficient for reducing MR or reversing the adverse LV remodeling. As LCZ696 is a dual-acting inhibitor of the renin-angiotensin-aldosterone system (RAAS) and neutral endopeptidase (NEP), LCZ696 has greater hemodynamic and neurohormonal effects than ARB alone. Investigators try to examine the hypothesis that LCZ696 is superior to ARB alone in improving functional MR in patients with LV dysfunction and functional MR.

Conditions

Mitral Valve Insufficiency; Left Ventricular Dysfunction

Keywords

Functional Mitral Regurgitation; Ischemic Mitral Regurgitation

Outcome Measures

Primary Outcomes (1)

• Change of effective regurgitant orifice area (EROA) of functional mitral regurgitation from baseline to 12 months follow-up

  12 months

Secondary Outcomes (4)

• Change of regurgitant volume from baseline to 12 months follow-up

  12 months

• Change of left ventricular end-systolic volume from baseline to 12 months follow-up

  12 months

• Change of left ventricular end-diastolic volume from baseline to 12 months follow-up

  12 months

• Change of incomplete mitral leaflet closure area from baseline to 12 months follow-up

  12 months

Study Arms (2)

LCZ696

EXPERIMENTAL

LCZ696 for 12 months

Drug: LCZ696

Valsartan

ACTIVE COMPARATOR

Valsartan for 12 months

Drug: Valsartan

Interventions

LCZ696 DRUG

LCZ696

Valsartan DRUG

Valsartan

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must agree to the study protocol and provide written informed consent
• Outpatients ≥ 20 years of age, male or female
• Patients with secondary functional MR (stage B and C) and LV dysfunction
• Symptoms due to coronary ischemia or heart failure may be present but symptoms due to MR should be absent
• Normal mitral valve leaflets and chords
• Regional or global wall motion abnormalities with mild or severe tethering of leaflet
• ERO \> 0.10 cm2
• % \< LV ejection fraction \< 50%
• Dyspnea of NYHA functional class II or III
• Patients must be on stable, optimized dose of an ACE inhibitors or ARBs for at least 4 weeks prior to study entry

You may not qualify if:

• History of hypersensitivity or allergy to the study drug, drugs of similar chemical classes, ARBs, or NEP inhibitors as well as known or suspected contraindications to the study drug
• Known history of angioedema
• Any evidence of structural mitral valve disease, including prolapse of mitral leaflets and rupture of chords or papillary muscles
• Current acute decompensated heart failure or dyspnea of NYHA functional class IV
• Medical history of hospitalization within 6 weeks
• Symptomatic hypotension and/or a SBP \< 100 mmHg at screening
• Estimated GFR \< 30 mL/min/1.73m2
• Serum potassium \> 5 mmol/L at screening
• Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 2 x upper limit of normal (ULN) at screening visit (Visit 0), history of hepatic encephalopathy, history of esophageal varices, or history of portacaval shunt
• Acute coronary syndrome, stroke, major CV surgery, PCI within 3 months
• Planned coronary revascularization or mitral valve intervention within 1 year
• Heart transplantation or implantation of cardiac resynchronization therapy
• History of severe pulmonary disease
• Significant aortic valve disease
• Primary aldosteronism

Sponsors & Collaborators

• Asan Medical Center: lead
• Novartis: collaborator

Study Sites (4)

Inha University Hospital

Incheon, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Yonsei University Medical Center

Seoul, South Korea

Location

Related Publications (1)

• Kang DH, Park SJ, Shin SH, Hong GR, Lee S, Kim MS, Yun SC, Song JM, Park SW, Kim JJ. Angiotensin Receptor Neprilysin Inhibitor for Functional Mitral Regurgitation. Circulation. 2019 Mar 12;139(11):1354-1365. doi: 10.1161/CIRCULATIONAHA.118.037077.

  PMID: 30586756 DERIVED

MeSH Terms

Conditions

Mitral Valve Insufficiency; Ventricular Dysfunction, Left

Interventions

sacubitril and valsartan sodium hydrate drug combination; Valsartan

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Duk-Hyun Kang, M.D.

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 17, 2016
• First Posted: February 22, 2016
• Study Start: March 1, 2016
• Primary Completion: January 2, 2018
• Study Completion: January 2, 2018
• Last Updated: January 9, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (4)