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

• ClinicalTrials.gov Identifier: NCT02661217
• Recruitment Status: Completed
• First Posted: January 22, 2016
• Results First Posted: April 26, 2021
• Last Update Posted: April 26, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: January 19, 2016
• First Posted Date: January 22, 2016
• Results First Submitted Date: June 20, 2019
• Results First Posted Date: April 26, 2021
• Last Update Posted Date: April 26, 2021
• Actual Study Start Date: February 12, 2016
• Actual Primary Completion Date: February 20, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 29, 2021)

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

Original Primary Outcome Measures (submitted: January 19, 2016)

Percentage of patients who are receiving 200 mg LCZ696 bid [ Time Frame: 10 weeks after Randomization ]

Assessing the percentage of patients who achieve the target dose of 200 mg bid LCZ696 at 10 weeks after randomization

Current Secondary Outcome Measures (submitted: March 29, 2021)

• 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
• 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
• 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

Original Secondary Outcome Measures (submitted: January 19, 2016)

• Number of patients who achieved and maintained either the dose of 100 mg and/or 200 mg LCZ696 bid for at least 2 weeks [ Time Frame: 10 weeks after Randomization ]
  Assessing number of patients achieving and maintaining either dose of 100 mg and/or 200 mg LCZ696 bid for at least 2 weeks
• Number of patients who, regardless of previous dose changes, achieved any dose of LCZ696 bid for at least 2 weeks [ Time Frame: 10 weeks after Randomization ]
  Assessing number of patients achieving and maintaining any dose of LCZ696 bid for at least 2 weeks
• Percentage of patients permanently discontinued from treatment due to Adverse Events [ Time Frame: 10 weeks after Randomization AND 26 weeks ]
  Percentage of patients permanently discontinued from LCZ696 (1) up to week-10, and (2) up to week 26, due to AEs

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event
• Official Title: 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)
• Brief Summary: To explore two modalities of treatment initiation (Pre-discharge, and Post-discharge) with LCZ696 in HFrEF patients following stabilization after an ADHF episode.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Supportive Care
• Condition: Heart Failure With Reduced Ejection Fraction

Intervention

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.

Study Arms

• Pre-discharge treatment initiation
  Patients received first dose at any point after Randomization but no later than 12 h before discharge.
  Intervention: Drug: LCZ696
• Post-discharge treatment initiation
  Patients received first dose after discharge and up to 14 days thereafter.
  Intervention: Drug: LCZ696

Publications *

• Pascual-Figal D, Wachter R, Senni M, Bao W, Noè A, Schwende H, Butylin D, Prescott MF; TRANSITION Investigators. NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study. JACC Heart Fail. 2020 Oct;8(10):822-833. doi: 10.1016/j.jchf.2020.05.012. Epub 2020 Aug 12.
• Senni M, Wachter R, Witte KK, Straburzynska-Migaj E, Belohlavek J, Fonseca C, Mueller C, Lonn E, Chakrabarti A, Bao W, Noe A, Schwende H, Butylin D, Pascual-Figal D; TRANSITION Investigators. Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study. Eur J Heart Fail. 2020 Feb;22(2):303-312. doi: 10.1002/ejhf.1670. Epub 2019 Dec 9.
• Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z, Fonseca C, Goncalvesova E, Cavusoglu Y, Fernandez A, Chaaban S, Bøhmer E, Pouleur AC, Mueller C, Tribouilloy C, Lonn E, A L Buraiki J, Gniot J, Mozheiko M, Lelonek M, Noè A, Schwende H, Bao W, Butylin D, Pascual-Figal D; TRANSITION Investigators. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. Eur J Heart Fail. 2019 Aug;21(8):998-1007. doi: 10.1002/ejhf.1498. Epub 2019 May 27.
• Pascual-Figal D, Wachter R, Senni M, Belohlavek J, Noè A, Carr D, Butylin D. Rationale and design of TRANSITION: a randomized trial of pre-discharge vs. post-discharge initiation of sacubitril/valsartan. ESC Heart Fail. 2018 Apr;5(2):327-336. doi: 10.1002/ehf2.12246. Epub 2017 Dec 14.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 29, 2021): 1002
• Original Estimated Enrollment (submitted: January 19, 2016): 1000
• Actual Study Completion Date: June 20, 2018
• Actual Primary Completion Date: February 20, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Belgium, Canada, Czechia, France, Germany, Italy, Lebanon, Norway, Poland, Portugal, Russian Federation, Saudi Arabia, Slovakia, Spain, Sweden, Switzerland, Turkey, United Kingdom
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02661217
• Other Study ID Numbers: CLCZ696B2401; 2015-003266-87 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: March 2021