Safety and Tolerability of Initiating LCZ696 in Heart Failure Patients (TITRATION)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01922089 |
Recruitment Status :
Completed
First Posted : August 14, 2013
Results First Posted : October 15, 2015
Last Update Posted : October 15, 2015
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Heart Failure With Reduced Ejection Fraction | Drug: LCZ696 | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 498 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Multicenter, Randomized, Double-blind, Parallel Group Study to Assess the Safety and Tolerability of Initiating LCZ696 in Heart Failure Patients Comparing Two Titration Regimens |
Study Start Date : | November 2013 |
Actual Primary Completion Date : | August 2014 |
Actual Study Completion Date : | August 2014 |

Arm | Intervention/treatment |
---|---|
Experimental: LCZ696 Condensed
Up-titration to LCZ696 200 mg twice daily (bid) over 3 weeks
|
Drug: LCZ696
LCZ696 50 mg/100 mg/200 mg bid |
Experimental: LCZ696 Conservative
Up-titration to LCZ696 200 mg bid over 6 weeks
|
Drug: LCZ696
LCZ696 50 mg/100 mg/200 mg bid |
- Number of Participants Experiencing Hypotension, Renal Dysfunction, Hyperkalemia and Angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low) [ Time Frame: 12 weeks ]Participants experiencing hypotension, renal dysfunction, hyperkalemia and angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) stratum (high vs. low) High RAAS stratum Patients receiving > 160 mg of valsartan or > 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening Low RAAS stratum: Patients receiving ≤ 160 mg of valsartan or ≤ 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening. This stratum also included patients who were not on an ACEI or an ARB 4 weeks prior to screening (i.e., ACEI/ARB-naïve patients)
- Number of Participants Who Achieved Treatment Success Over the 12 Weeks and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low) [ Time Frame: 12 weeks ]Treatment success was defined as the number of participants who achieved and maintained LCZ696 200 mg bid without any dose interruption or down-titration over 12 weeks and by Renin-Angiotensin-Aldosterone System (RAAS) stratum (high vs. low) High RAAS stratum Patients receiving > 160 mg of valsartan or > 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening Low RAAS stratum: Patients receiving ≤ 160 mg of valsartan or ≤ 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening. This stratum also included patients who were not on an ACEI or an ARB 4 weeks prior to screening (i.e., ACEI/ARB-naïve patients)
- Number of Participants Who Tolerated Study Medication for at Least the Last Two Weeks of the Study and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low). [ Time Frame: 12 weeks ]Tolerability was assessed as the number of participants who achieved LCZ696 200 mg bid and maintained this dose for at least 2 weeks before study completion, regardless of previous dose interruption or down-titration and by Renin-Angiotensin-Aldosterone System (RAAS) stratum (high vs. low) High RAAS stratum Patients receiving > 160 mg of valsartan or > 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening Low RAAS stratum: Patients receiving ≤ 160 mg of valsartan or ≤ 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening. This stratum also included patients who were not on an ACEI or an ARB 4 weeks prior to screening (i.e., ACEI/ARB-naïve patients)

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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age ≥ 18 years; CHF with New York Heart Association class II-IV; left ventricular ejection fraction ≤ 35%; on beta blockers
Exclusion Criteria:
- Potassium > 5.2 mmol/l; estimated glomerular filtration rate < 30 ml/min/1.73 m2; systolic blood pressure <100 mmHg or > 180 mmHg; history of intolerance to recommended target doses of angiotensin converting enzyme inhibitors or angiotensin receptor blockers
Other protocol-defined inclusion/exclusion criteria may apply.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01922089

Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT01922089 |
Other Study ID Numbers: |
CLCZ696B2228 2013-001835-33 ( EudraCT Number ) |
First Posted: | August 14, 2013 Key Record Dates |
Results First Posted: | October 15, 2015 |
Last Update Posted: | October 15, 2015 |
Last Verified: | September 2015 |
Heart failure, reduced ejection fraction, LCZ696, titration, safety, tolerability |
Heart Failure Heart Diseases Cardiovascular Diseases |
Sacubitril and valsartan sodium hydrate drug combination Angiotensin Receptor Antagonists Molecular Mechanisms of Pharmacological Action |