Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event (TRANSITION)

March 29, 2021 updated by: Novartis Pharmaceuticals

A Multicenter, Randomized, Open Label, Parallel Group Study Comparing Pre-discharge and posT-discharge tReatment Initiation With LCZ696 in heArt Failure patieNtS With Reduced ejectIon-fracTion hospItalized for an Acute decOmpensation eveNt (ADHF)

To explore two modalities of treatment initiation (Pre-discharge, and Post-discharge) with LCZ696 in HFrEF patients following stabilization after an ADHF episode.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1002

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1405CNF
        • Novartis Investigative Site
      • Buenos Aires, Argentina, C1426BOR
        • Novartis Investigative Site
      • Cordoba, Argentina, X5000
        • Novartis Investigative Site
      • Salta, Argentina, 4400
        • Novartis Investigative Site
      • Tucuman, Argentina, T4000NIJ
        • Novartis Investigative Site
    • Buenos Aires
      • Quilmes, Buenos Aires, Argentina, B1878DKF
        • Novartis Investigative Site
    • Cordoba
      • Villa Maria, Cordoba, Argentina, X5900JKA
        • Novartis Investigative Site
  • Belgium
      • Bruxelles, Belgium, 1200
        • Novartis Investigative Site
      • Genk, Belgium, 3600
        • Novartis Investigative Site
      • Huy, Belgium, 4500
        • Novartis Investigative Site
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
      • Ronse, Belgium, 9600
        • Novartis Investigative Site
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Novartis Investigative Site
    • Ontario
      • Hamilton, Ontario, Canada, L8L 2X2
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H3A 1A1
        • Novartis Investigative Site
  • Czechia
      • Brno Bohunice, Czechia, 625 00
        • Novartis Investigative Site
      • JIhlava, Czechia, 586 01
        • Novartis Investigative Site
      • Kolin, Czechia, 280 20
        • Novartis Investigative Site
      • Olomouc, Czechia, 775 20
        • Novartis Investigative Site
      • Praha, Czechia, 12808
        • Novartis Investigative Site
      • Praha 10, Czechia, 100 34
        • Novartis Investigative Site
      • Slany, Czechia, 274 01
        • Novartis Investigative Site
    • CZE
      • Beroun, CZE, Czechia, 26601
        • Novartis Investigative Site
      • Ostrava, CZE, Czechia, 72880
        • Novartis Investigative Site
    • Czech Republic
      • Brno, Czech Republic, Czechia, 656 91
        • Novartis Investigative Site
      • Karlovy Vary, Czech Republic, Czechia, 360 66
        • Novartis Investigative Site
      • Liberec, Czech Republic, Czechia, 460 63
        • Novartis Investigative Site
      • Tabor, Czech Republic, Czechia, 39003
        • Novartis Investigative Site
      • Trebic, Czech Republic, Czechia, 674 01
        • Novartis Investigative Site
  • France
      • Amiens, France, 80054
        • Novartis Investigative Site
      • Besancon cedex, France, 25030
        • Novartis Investigative Site
      • Paris, France, 75012
        • Novartis Investigative Site
      • Paris cedex 10, France, 75010
        • Novartis Investigative Site
      • Toulouse Cedex, France, 31059
        • Novartis Investigative Site
      • Tourcoing, France, 59200
        • Novartis Investigative Site
      • Valenciennes, France, 59300
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 13353
        • Novartis Investigative Site
      • Dortmund, Germany, 44379
        • Novartis Investigative Site
      • Erfurt, Germany, 99089
        • Novartis Investigative Site
      • Essen, Germany, 45356
        • Novartis Investigative Site
      • Frankfurt, Germany, 65929
        • Novartis Investigative Site
      • Gottingen, Germany, 37075
        • Novartis Investigative Site
      • Hamburg, Germany, 20246
        • Novartis Investigative Site
      • Jena, Germany, 07740
        • Novartis Investigative Site
      • Koeln-Nippes, Germany, 50733
        • Novartis Investigative Site
      • Langen, Germany, 63225
        • Novartis Investigative Site
      • Lübeck, Germany, 23569
        • Novartis Investigative Site
      • Magdeburg, Germany, 39120
        • Novartis Investigative Site
      • Mainz, Germany, 55131
        • Novartis Investigative Site
      • Moenchengladbach, Germany, 41063
        • Novartis Investigative Site
      • Neuwied, Germany, 56564
        • Novartis Investigative Site
      • Oldenburg, Germany, 26133
        • Novartis Investigative Site
      • Ruesselsheim, Germany, 65428
        • Novartis Investigative Site
      • Witten, Germany, 58455
        • Novartis Investigative Site
    • Baden-Wuerttemberg
      • Mannheim, Baden-Wuerttemberg, Germany, 68305
        • Novartis Investigative Site
    • Bavaria
      • Regensburg, Bavaria, Germany, 93053
        • Novartis Investigative Site
    • Nordrhein-Westfalen
      • Leverkusen, Nordrhein-Westfalen, Germany, 51375
        • Novartis Investigative Site
  • Italy
      • Milano, Italy, 20142
        • Novartis Investigative Site
    • BG
      • Bergamo, BG, Italy, 24127
        • Novartis Investigative Site
    • CR
      • Cremona, CR, Italy, 26100
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00152
        • Novartis Investigative Site
  • Lebanon
      • Ashrafieh, Lebanon, 166830
        • Novartis Investigative Site
      • Beirut, Lebanon, 1107 2020
        • Novartis Investigative Site
      • Beirut, Lebanon
        • Novartis Investigative Site
      • Saida, Lebanon, 652
        • Novartis Investigative Site
    • LBN
      • El Chouf, LBN, Lebanon, 1503201002
        • Novartis Investigative Site
  • Norway
      • Alesund, Norway, NO-6026
        • Novartis Investigative Site
      • Bergen, Norway, 5009
        • Novartis Investigative Site
      • Gralum, Norway, 1714
        • Novartis Investigative Site
      • Lillehammer, Norway, 2629
        • Novartis Investigative Site
  • Poland
      • Bialystok, Poland, 15-276
        • Novartis Investigative Site
      • Krakow, Poland, 31202
        • Novartis Investigative Site
      • Poznan, Poland, 61-848
        • Novartis Investigative Site
      • Pulawy, Poland, 24100
        • Novartis Investigative Site
      • Warszawa, Poland, 04-749
        • Novartis Investigative Site
      • Wroclaw, Poland, 50 420
        • Novartis Investigative Site
    • Lodzkie
      • Lodz, Lodzkie, Poland, 90 549
        • Novartis Investigative Site
  • Portugal
      • Amadora, Portugal, 2720-276
        • Novartis Investigative Site
      • Aveiro, Portugal, 3814-501
        • Novartis Investigative Site
      • Coimbra, Portugal, 3000-075
        • Novartis Investigative Site
      • Covilha, Portugal, 6200-251
        • Novartis Investigative Site
      • Guimaraes, Portugal, 4835-044
        • Novartis Investigative Site
      • Leiria, Portugal, 2410-187
        • Novartis Investigative Site
      • Lisboa, Portugal, 1649-035
        • Novartis Investigative Site
      • Lisboa, Portugal, 1495 005
        • Novartis Investigative Site
      • Lisboa, Portugal, 1500 650
        • Novartis Investigative Site
      • Porto, Portugal, 4099-001
        • Novartis Investigative Site
      • Porto, Portugal, 4200-319
        • Novartis Investigative Site
    • Portuigal
      • Vila Real, Portuigal, Portugal, 5000-508
        • Novartis Investigative Site
  • Russian Federation
      • Gatchina, Russian Federation, 188300
        • Novartis Investigative Site
      • Kazan, Russian Federation, 420012
        • Novartis Investigative Site
      • Moscow, Russian Federation, 117292
        • Novartis Investigative Site
      • Moscow, Russian Federation, 117556
        • Novartis Investigative Site
      • Moscow, Russian Federation, 123182
        • Novartis Investigative Site
      • Saint Petersburg, Russian Federation, 199106
        • Novartis Investigative Site
      • Saint Petersburg, Russian Federation, 193312
        • Novartis Investigative Site
      • Yaroslavl, Russian Federation, 150047
        • Novartis Investigative Site
  • Saudi Arabia
      • Dammam, Saudi Arabia, 31463
        • Novartis Investigative Site
      • Jeddah, Saudi Arabia, 21499
        • Novartis Investigative Site
      • Riyadh, Saudi Arabia, 11211
        • Novartis Investigative Site
  • Slovakia
      • Bratislava, Slovakia, 826 06
        • Novartis Investigative Site
      • Bratislava, Slovakia, 833 48
        • Novartis Investigative Site
      • Dolny Kubin, Slovakia, 026 01
        • Novartis Investigative Site
      • Martin, Slovakia, 036 59
        • Novartis Investigative Site
      • Presov, Slovakia, 080 01
        • Novartis Investigative Site
      • Rimavska Sobota, Slovakia, 97912
        • Novartis Investigative Site
      • Trnava, Slovakia, 917 75
        • Novartis Investigative Site
    • Slovak Republic
      • Dunajska Streda, Slovak Republic, Slovakia, 92901
        • Novartis Investigative Site
      • Kosice, Slovak Republic, Slovakia, 4190
        • Novartis Investigative Site
      • Liptovsky Mikulas, Slovak Republic, Slovakia, 031 23
        • Novartis Investigative Site
  • Spain
      • Las Palmas de Gran Canaria, Spain, 35010
        • Novartis Investigative Site
      • Madrid, Spain, 28222
        • Novartis Investigative Site
    • Andalucia
      • Malaga, Andalucia, Spain, 29010
        • Novartis Investigative Site
      • Sanlucar de Barrameda, Andalucia, Spain, 11540
        • Novartis Investigative Site
      • Sevilla, Andalucia, Spain, 41009
        • Novartis Investigative Site
      • Sevilla, Andalucia, Spain, 41014
        • Novartis Investigative Site
    • Barcelona/ Cataluny/Espanya
      • Barcelona, Barcelona/ Cataluny/Espanya, Spain, 08035
        • Novartis Investigative Site
    • Cadiz
      • Villamartin, Cadiz, Spain, 11650
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46014
        • Novartis Investigative Site
      • Valencia, Comunidad Valenciana, Spain, 46026
        • Novartis Investigative Site
      • Valencia, Comunidad Valenciana, Spain, 46010
        • Novartis Investigative Site
    • Galicia
      • A Coruna, Galicia, Spain, 15006
        • Novartis Investigative Site
      • La Coruna, Galicia, Spain, 15006
        • Novartis Investigative Site
    • Girona
      • Olot, Girona, Spain, 17800
        • Novartis Investigative Site
    • Madrid
      • Mostoles, Madrid, Spain, 28935
        • Novartis Investigative Site
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Novartis Investigative Site
  • Sweden
      • Goteborg, Sweden, 413 45
        • Novartis Investigative Site
      • Joenkoeping, Sweden, 551 85
        • Novartis Investigative Site
  • Switzerland
      • Basel, Switzerland, 4031
        • Novartis Investigative Site
      • Geneve 14, Switzerland, 1211
        • Novartis Investigative Site
  • Turkey
      • Ankara, Turkey, 06100
        • Novartis Investigative Site
      • Istanbul, Turkey, 34304
        • Novartis Investigative Site
      • Kocaeli, Turkey, 41380
        • Novartis Investigative Site
      • Mersin, Turkey, 33343
        • Novartis Investigative Site
      • Sivas, Turkey, 58140
        • Novartis Investigative Site
    • Meselik
      • Eskisehir, Meselik, Turkey, 26480
        • Novartis Investigative Site
  • United Kingdom
      • Blackpool, United Kingdom, FY3 8NR
        • Novartis Investigative Site
      • Leeds, United Kingdom, LS1 3EX
        • Novartis Investigative Site
      • Leicester, United Kingdom, LE 3 9QP
        • Novartis Investigative Site
      • Liverpool, United Kingdom, L9 7AL
        • Novartis Investigative Site
      • London, United Kingdom, EC14 7BE
        • Novartis Investigative Site
      • Middlesbrough, United Kingdom, TS4 3BW
        • Novartis Investigative Site
      • Newcastle Upon Tyne, United Kingdom, NE1 4LP
        • Novartis Investigative Site
      • Norwich, United Kingdom, NR4 7UY
        • Novartis Investigative Site
      • Swindon, United Kingdom, SN3 6BB
        • Novartis Investigative Site
      • York, United Kingdom, YO31 8HE
        • Novartis Investigative Site
    • Essex
      • Westcliff on Sea, Essex, United Kingdom, SS0 0RY
        • Novartis Investigative Site
    • Hampshire
      • Basingstoke, Hampshire, United Kingdom, RG24 9NA
        • Novartis Investigative Site
    • Kent
      • Ashford, Kent, United Kingdom, TN24 0LZ
        • Novartis Investigative Site
    • Mid Glamorgan
      • Bridgend, Mid Glamorgan, United Kingdom, CF31 1RQ
        • Novartis Investigative Site
    • Nothern Ireland
      • Portadown, Nothern Ireland, United Kingdom, BT63 5QQ
        • Novartis Investigative Site
    • Tyne And Wear
      • Sunderland, Tyne And Wear, United Kingdom, SR4 7TP
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients hospitalized due to acute decompensated HF episode (ADHF) as primary diagnosis) and consistent Signs & Symptoms
  2. Diagnosis of HF New York Heart Association class II-to-IV and reduced ejection fraction: Left ventricular ejection fraction ≤ 40% at Screening
  3. Patients did not receive any IV vasodilators (except nitrates), and/or any IV inotropic therapy from the time of presentation for ADHF to Randomization
  4. Stabilized (while in the hospital) for at least 24 hours leading to Randomization.

  5. Meeting one of the following criteria:

    • Patients on any dose of ACEI or ARB at screening
    • ACEI/ARB naïve patients and patients not on ACEI or ARB for at least 4 weeks before screening.

Exclusion Criteria:

  1. History of hypersensitivity to the sacubitril, valsartan, or any ARBs, NEP inhibitors or to any of the LCZ696 excipients.
  2. Symptomatic hypotension and/or a SBP below 110 mm Hg or SBP above 180 mm Hg prior to randomization
  3. End stage renal disease at Screening; or estimated GFR below 30 mL/min/1.73 m2 (as measured by MDRD formula at Randomization.
  4. Serum potassium above 5.4 mmol/L at Randomization.
  5. Known history of hereditary or idiopathic angioedema or angioedema related to previous ACE inhibitor or ARB therapy
  6. Severe hepatic impairment, biliary cirrhosis and cholestasis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Pre-discharge treatment initiation
Patients received first dose at any point after Randomization but no later than 12 h before discharge.
Drug: LCZ696

LCZ696 film-coated tables were supplied to the investigators. Tablets were taken with a glass of water, and were administered with or without food.

The target dose of LCZ696 was 200 mg twice daily. Starting dose of LCZ696 was either 50 or 100 mg, twice daily. The dose of LCZ696 should be doubled every 2-4 weeks to achieve the target dose of 200 mg twice daily, as tolerated by the patient.
Other: Post-discharge treatment initiation
Patients received first dose after discharge and up to 14 days thereafter.
Drug: LCZ696

LCZ696 film-coated tables were supplied to the investigators. Tablets were taken with a glass of water, and were administered with or without food.

The target dose of LCZ696 was 200 mg twice daily. Starting dose of LCZ696 was either 50 or 100 mg, twice daily. The dose of LCZ696 should be doubled every 2-4 weeks to achieve the target dose of 200 mg twice daily, as tolerated by the patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients Achieving the Target Dose of LCZ696 200 mg Bid at 10 Weeks Post Randomization
Time Frame: 10 weeks after Randomization
Percentage of patients achieving and maintaining LCZ696 200 mg bid for at least 2 weeks leading to Week 10
10 weeks after Randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients Achieving and Maintaining Either LCZ696 100 mg and/or 200 mg Bid
Time Frame: 10 weeks after Randomization
Percentage of patients achieving and maintaining either LCZ696 100 mg and/or 200 mg bid for at least 2 weeks leading to Week 10
10 weeks after Randomization
Percentage of Patients Achieving and Maintaining Any Dose of LCZ696
Time Frame: 10 weeks after Randomization
Percentage of patients achieving any dose of LCZ696 for at least 2 weeks leading to 10 weeks of treatment
10 weeks after Randomization
Percentage of Patients Permanently Discontinued From Treatment
Time Frame: 10 weeks after Randomization AND 26 weeks after randomization
Percentage of patients permanently discontinued from LCZ696 (1) up to week 10 due to AEs, and (2) up to week 26 due to any reasons
10 weeks after Randomization AND 26 weeks after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 12, 2016

Primary Completion (Actual)

February 20, 2018

Study Completion (Actual)

June 20, 2018

Study Registration Dates

First Submitted

January 19, 2016

First Submitted That Met QC Criteria

January 19, 2016

First Posted (Estimate)

January 22, 2016

Study Record Updates

Last Update Posted (Actual)

April 26, 2021

Last Update Submitted That Met QC Criteria

March 29, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLCZ696B2401
  • 2015-003266-87 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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