Safety and Tolerability During Open-label Treatment With LCZ696 in Patients With CHF and Reduced Ejection Fraction
Condition: Chronic Heart Failure With Reduced Ejection Fraction
MeSH terms: Heart Failure
Intervention: LCZ696
Intervention description: Angiotensin receptor antagonist neprilysin inhibitor (ARNI) with target dose of 200 mg bid
Intervention MeSH terms: Sacubitril and valsartan sodium hydrate drug combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1980.0
Sex: All
Healthy volunteers: No
Keywords: LCZ696; chronic heart failure; ARNI; Congestive heart failure (CHF); heart failure (HF); acute heart failure syndrome; congestive cardiac failure (CCF)

Summary:

      The purpose of this study was to collect safety and tolerability data on LCZ696 in eligible
      PARADIGM-HF patients who received open-label investigational drug. The parent PARADIGM-HF
      (NCT01035255) trial was terminated early due to compelling efficacy of LCZ696 in patients
      with heart failure with reduced ejection fraction (HFrEF) after the final pre-specified
      interim analysis in March 2014.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent for the extension must be obtained before any assessment is
             performed.

          2. Patients who have completed PARADIGM-HF (protocol CLCZ696B2314) and are able to be
             safely enrolled into the open-label trial as judged by the investigator.

        Exclusion Criteria:

          1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5
             half-lives of enrollment, whichever is longer

          2. History of hypersensitivity or allergy to any of the study drugs, drugs of similar
             chemical classes, ACEIs, ARBs, or NEP inhibitors as well as known or suspected
             contraindications to LCZ696

          3. Known history of angioedema

          4. Requirement of simultaneous treatment with both ACEIs and ARBs

          5. Current acute decompensated HF (exacerbation of chronic HF manifested by signs and
             symptoms that may require intravenous therapy)

          6. Symptomatic hypotension and/or a SBP < 100 mmHg at Visit 1 (screening)

          7. Estimated GFR < 30 mL/min/1.73m^2 as measured by the simplified MDRD formula at Visit
             1 (screening)

          8. Presence of bilateral renal artery stenosis

          9. Serum potassium > 5.2 mmol/L at Visit 1 (screening)

         10. Evidence of hepatic disease as determined by any one of the following: AST or ALT
             values exceeding 3 x ULN at Visit 1, history of hepatic encephalopathy, history of
             esophageal varices, or history of portacaval shunt

         11. Pregnant or nursing (lactating) women

         12. Women of child-bearing potential

         13. Any condition, not identified in the protocol, that in the opinion of the investigator
             is likely to prevent the patient from safely tolerating LCZ696 or complying with the
             requirements of the study.