Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2013-001835-33 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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Not provided
The purpose of this study is to assess the safety and tolerability of initiating LCZ696 in heart failure patients with reduced ejection fraction (HF-rEF) using conservative (reaching target dose over 6 weeks) and condensed (reaching target dose over 3 weeks) up-titration regimens.
Not provided
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LCZ696 Condensed | Experimental | Up-titration to LCZ696 200 mg twice daily (bid) over 3 weeks |
|
| LCZ696 Conservative | Experimental | Up-titration to LCZ696 200 mg bid over 6 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LCZ696 | Drug | LCZ696 50 mg/100 mg/200 mg bid |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing Hypotension, Renal Dysfunction, Hyperkalemia and Angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low) | 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) | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Achieved Treatment Success Over the 12 Weeks and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low) | 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Anchorage | Alaska | 99508 | United States | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29164797 | Derived | Senni M, McMurray JJV, Wachter R, McIntyre HF, Anand IS, Duino V, Sarkar A, Shi V, Charney A. Impact of systolic blood pressure on the safety and tolerability of initiating and up-titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study. Eur J Heart Fail. 2018 Mar;20(3):491-500. doi: 10.1002/ejhf.1054. Epub 2017 Nov 22. | |
| 27170530 |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | LCZ696 Condensed | Up-titration to LCZ696 200 mg twice daily (bid) over 3 weeks |
| FG001 | LCZ696 Conservative | Up-titration to LCZ696 200 mg bid over 6 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 12 weeks |
| 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). | 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) | 12 weeks |
| Gilbert |
| Arizona |
| 85297 |
| United States |
| Novartis Investigative Site | Tucson | Arizona | 85710 | United States |
| Novartis Investigative Site | Anaheim | California | 92801 | United States |
| Novartis Investigative Site | Torrance | California | 90502 | United States |
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| Novartis Investigative Site | Evansville | Indiana | 47714 | United States |
| Novartis Investigative Site | Slidell | Louisiana | 70458 | United States |
| Novartis Investigative Site | Minneapolis | Minnesota | 55417 | United States |
| Novartis Investigative Site | St Louis | Missouri | 63110 | United States |
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| Novartis Investigative Site | Laurelton | New York | 11422 | United States |
| Novartis Investigative Site | Marion | Ohio | 43302 | United States |
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| Novartis Investigative Site | Dallas | Texas | 75231 | United States |
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| Novartis Investigative Site | Livingston | Texas | 77351 | United States |
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| Novartis Investigative Site | Gabrovo | Bulgaria | 5300 | Bulgaria |
| Novartis Investigative Site | Plovdiv | Bulgaria | 4000 | Bulgaria |
| Novartis Investigative Site | Plovdiv | Bulgaria | 4004 | Bulgaria |
| Novartis Investigative Site | Smolyan | Bulgaria | 4700 | Bulgaria |
| Novartis Investigative Site | Sofia | 1202 | Bulgaria |
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| Novartis Investigative Site | Jyväskylä | 40620 | Finland |
| Novartis Investigative Site | Tampere | 33520 | Finland |
| Novartis Investigative Site | Bad Krozingen | 79189 | Germany |
| Novartis Investigative Site | Berlin | 10367 | Germany |
| Novartis Investigative Site | Berlin | 10787 | Germany |
| Novartis Investigative Site | Berlin | 10789 | Germany |
| Novartis Investigative Site | Berlin | 13055 | Germany |
| Novartis Investigative Site | Berlin | 13347 | Germany |
| Novartis Investigative Site | Berlin | 13353 | Germany |
| Novartis Investigative Site | Berlin | 13405 | Germany |
| Novartis Investigative Site | Buch | 13125 | Germany |
| Novartis Investigative Site | Dietzenbach | 63128 | Germany |
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| Novartis Investigative Site | Huy / OT Anderbeck | 38836 | Germany |
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| Novartis Investigative Site | Würzburg | 97078 | Germany |
| Novartis Investigative Site | Budapest | 1042 | Hungary |
| Novartis Investigative Site | Budapest | 1145 | Hungary |
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| Novartis Investigative Site | Debrecen | 4032 | Hungary |
| Novartis Investigative Site | Mosonmagyaróvár | 9200 | Hungary |
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| Novartis Investigative Site | Pécs | 7623 | Hungary |
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| Novartis Investigative Site | Aosta | AO | 11100 | Italy |
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| Novartis Investigative Site | Bergamo | BG | 24128 | Italy |
| Novartis Investigative Site | Bologna | BO | 40138 | Italy |
| Novartis Investigative Site | Cona | FE | 44100 | Italy |
| Novartis Investigative Site | Albano Laziale | RM | 00041 | Italy |
| Novartis Investigative Site | Roma | RM | 00163 | Italy |
| Novartis Investigative Site | Sassari | SS | 07100 | Italy |
| Novartis Investigative Site | Vittorio Veneto | TV | 31029 | Italy |
| Novartis Investigative Site | San Daniele del Friuli | UD | 33038 | Italy |
| Novartis Investigative Site | San Juan | 00936-6528 | Puerto Rico |
| Novartis Investigative Site | Brezno | Slovak Republic | 977 42 | Slovakia |
| Novartis Investigative Site | Nitra | Slovak Republic | 949 01 | Slovakia |
| Novartis Investigative Site | Svidník | Slovak Republic | 08901 | Slovakia |
| Novartis Investigative Site | Bratislava | Slovakia | 821 07 | Slovakia |
| Novartis Investigative Site | Bratislava | Slovakia | 83301 | Slovakia |
| Novartis Investigative Site | Košice | Slovakia | 040 01 | Slovakia |
| Novartis Investigative Site | Lučenec | Slovakia | 98439 | Slovakia |
| Novartis Investigative Site | Nové Zámky | Slovakia | 940 01 | Slovakia |
| Novartis Investigative Site | Trebišov | Slovakia | 075 01 | Slovakia |
| Novartis Investigative Site | Almería | Andalusia | 04120 | Spain |
| Novartis Investigative Site | Málaga | Andalusia | 29010 | Spain |
| Novartis Investigative Site | Sanlúcar de Barrameda | Andalusia | 11540 | Spain |
| Novartis Investigative Site | Seville | Andalusia | 41014 | Spain |
| Novartis Investigative Site | Villamartín | Cadiz | 11650 | Spain |
| Novartis Investigative Site | Barcelona | Catalonia | 08035 | Spain |
| Novartis Investigative Site | A Coruña | Galicia | 15006 | Spain |
| Novartis Investigative Site | Madrid | Madrid | 28007 | Spain |
| Novartis Investigative Site | Istanbul | Turkey | 34304 | Turkey (Türkiye) |
| Novartis Investigative Site | Haydarpasa/Istanbul | 34668 | Turkey (Türkiye) |
| Novartis Investigative Site | Kocaeli | 41380 | Turkey (Türkiye) |
| Novartis Investigative Site | Mersin | 33079 | Turkey (Türkiye) |
| Novartis Investigative Site | Sivas | 58140 | Turkey (Türkiye) |
| Novartis Investigative Site | Dorchester | Dorset | DT1 2JY | United Kingdom |
| Novartis Investigative Site | Saint Leonards-on-Sea | East Sussex | TN37 7RD | United Kingdom |
| Novartis Investigative Site | Oldham | Lancashire | OL1 2JH | United Kingdom |
| Novartis Investigative Site | Gateshead | Tyne and Wear | NE9 6SX | United Kingdom |
| Novartis Investigative Site | Bath | BA1 3NG | United Kingdom |
| Novartis Investigative Site | Bradford | BD9 6RJ | United Kingdom |
| Novartis Investigative Site | Coventry | CV2 2DX | United Kingdom |
| Novartis Investigative Site | Harrow | HA1 3UJ | United Kingdom |
| Novartis Investigative Site | Nuneaton | CV10 7DJ | United Kingdom |
| Derived |
| Senni M, McMurray JJ, Wachter R, McIntyre HF, Reyes A, Majercak I, Andreka P, Shehova-Yankova N, Anand I, Yilmaz MB, Gogia H, Martinez-Selles M, Fischer S, Zilahi Z, Cosmi F, Gelev V, Galve E, Gomez-Doblas JJ, Nociar J, Radomska M, Sokolova B, Volterrani M, Sarkar A, Reimund B, Chen F, Charney A. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail. 2016 Sep;18(9):1193-202. doi: 10.1002/ejhf.548. Epub 2016 May 12. |
| Safety Set |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | LCZ696 Condensed | Up-titration to LCZ696 200 mg twice daily (bid) over 3 weeks |
| BG001 | LCZ696 Conservative | Up-titration to LCZ696 200 mg bid over 6 weeks |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Experiencing Hypotension, Renal Dysfunction, Hyperkalemia and Angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low) | 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) | Full Analysis Set (FAS) consisted of all randomized patients with the exception of mis-randomized patients who had not received the study drug, but had been inadvertently randomized into the study. Following the intent-to-treat principle, patients were analyzed according to the treatment to which they were assigned at randomization. | Posted | Number | participants | 12 weeks |
|
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Achieved Treatment Success Over the 12 Weeks and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low) | 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) | Evaluable patients in FAS with the exception of misrandomized patients who didn't received drug, but had been randomized into the study, excluding patients who discontinued the study prior to completion of 12 wks. Following the intent-to-treat principle, patients were analyzed according to the treatment to which they were assigned at randomization. | Posted | Number | participants | 12 weeks |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | 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). | 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) | Evaluable patients in FAS with the exception of misrandomized patients who didn't received drug, but had been randomized into the study, excluding patients who discontinued the study prior to completion of 12 wks. Following the intent-to-treat principle, patients were analyzed according to the treatment to which they were assigned at randomization. | Posted | Number | participants | 12 weeks |
|
Not provided
Hyperkalemia in primary outcome is when patient experiences any AE after randomization with preferred term Hyperkalaemia or Blood potassium increased and AE table has incidences of AEs on or after randomization by preferred terms which exceeds a threshold of 2%. therefore 3 less cases than Primary OM.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LCZ696 Condensed | Up-titration to LCZ696 200 mg twice daily (bid) over 3 weeks | 21 | 246 | 72 | 246 | ||
| EG001 | LCZ696 Conservative | Up-titration to LCZ696 200 mg bid over 6 weeks | 14 | 251 | 52 | 251 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac failure chronic | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac ventricular thrombosis | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiogenic shock | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Coronary artery stenosis | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Ventricular fibrillation | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Cardiac death | General disorders | MedDRA | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Hepatic cyst | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Gastrointestinal infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Infected skin ulcer | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Procedural complication | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA | Systematic Assessment |
| |
| Bladder neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Renal failure chronic | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Postmenopausal haemorrhage | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C549068 | sacubitril and valsartan sodium hydrate drug combination |
Not provided
Not provided
Not provided
| Male |
|
| Hypotension ALL |
|
| Renal Dysfunction High RAAS (n=120, 127) |
|
| Renal Dysfunction Low RAAS (n=127, 124) |
|
| Renal Dysfunction ALL |
|
| Hyperkalemia High RAAS (n=120, 127) |
|
| Hyperkalemia Low RAAS (n=127, 124) |
|
| Hyperkalemia ALL |
|
| Angioedema High RAAS (n=120, 127) |
|
| Angioedema Low RAAS (n=127, 124) |
|
| Angioedema ALL |
|
|
|
Up-titration to LCZ696 200 mg bid over 6 weeks
|
|