Pharmacological Reduction of Functional, Ischemic Mitral REgurgitation

• Status: Completed
• Trial end date: 2018-01-02
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Asan Medical Center
• Collaborator: Novartis
• Treatments: LCZ 696; Sacubitril and valsartan sodium hydrate drug combination; Valsartan

Criteria

Inclusion Criteria:

1. Patients must agree to the study protocol and provide written informed consent

2. Outpatients ≥ 20 years of age, male or female

3. 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

• 25% < LV ejection fraction < 50%

4. Dyspnea of NYHA functional class II or III

5. Patients must be on stable, optimized dose of an ACE inhibitors or ARBs for at least 4 weeks prior to study entry

Exclusion Criteria:

1. 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

2. Known history of angioedema

3. Any evidence of structural mitral valve disease, including prolapse of mitral leaflets and rupture of chords or papillary muscles

4. Current acute decompensated heart failure or dyspnea of NYHA functional class IV

5. Medical history of hospitalization within 6 weeks

6. Symptomatic hypotension and/or a SBP < 100 mmHg at screening

7. Estimated GFR < 30 mL/min/1.73m2

8. Serum potassium > 5 mmol/L at screening

9. 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

10. Acute coronary syndrome, stroke, major CV surgery, PCI within 3 months

11. Planned coronary revascularization or mitral valve intervention within 1 year

12. Heart transplantation or implantation of cardiac resynchronization therapy

13. History of severe pulmonary disease

14. Significant aortic valve disease

15. Primary aldosteronism

16. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using a barrier method plus a hormonal method

17. Pregnant or nursing (lactating) women

18. Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the investigator, would preclude safe completion of the study