Study to compare Pre-discharge and Post-discharge treatment initiation with LCZ696 therapy in heart failure patients with reduced ejection fraction (HF-rEF) after an acute decompensation event

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2015-003266-87-DE
• Date of registration: 01/12/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma services AG
• Public title: Study to compare Pre-discharge and Post-discharge treatment initiation with LCZ696 therapy in heart failure patients with reduced ejection fraction (HF-rEF) after an acute decompensation event
• Scientific 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) - the TRANSITION study
• Date of first enrolment: 02/03/2016
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003266-87
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Pre-discharge initiation of LCZ696 arm versus the Post-discharge initiation of LCZ696 arm; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Argentina, Australia, Belgium, Canada, Czech Republic, Finland, France, Germany, Hungary, Italy, Lebanon, Mexico, Norway, Poland, Portugal, Russian Federation, Saudi Arabia, Slovakia, Spain, Sweden, Switzerland, Turkey, United Arab Emirates, United Kingdom

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
- Patients hospitalized due to acute decompensated HF episode (ADHF)
- Diagnosis of HF New York Heart Association class II-to-IV and reduced ejection fraction
- Patients did not receive any IV vasodilators (except nitrates), and/or any IV inotropic therapy from the time of presentation for ADHF to randomization
- Stabilized (while in the hospital) for at least 24 hours leading to randomization
- Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 255
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1445

Exclusion criteria:
- Symptomatic hypotension and/or a SBP < 110 mm Hg or SBP > 180 mm Hg prior to randomization
- End stage renal disease at ccreening; or estimated GFR < 30 mL/min/1.73 m2 as measured by (MDRD) formula at randomization.
- Serum potassium > 5.4 mmol/L at randomization.
- Current hospitalization where patient does not receive treatment for decompensated HF.
- Known history of hereditary or idiopathic angioedema or angioedema related to previous ACE inhibitor or ARB therapy
- Severe hepatic impairment, biliary cirrhosis and cholestasis
- Other protocol-defined exclusion criteria may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Heart Failure with reduced ejection fraction (HF-rEF) stabilized after hospitalization due to acute decompensated heart failure episode.
MedDRA version: 19.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Trade Name: ENTRESTO
Product Name: LCZ696 50 mg
Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SACUBITRIL/VALSARTAN
Other descriptive name: SACUBITRIL VALSARTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: ENTRESTO
Product Name: LCZ696 100 mg
Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SACUBITRIL/VALSARTAN
Other descriptive name: SACUBITRIL VALSARTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: ENTRESTO
Product Name: LCZ696 200 mg
Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SACUBITRIL/VALSARTAN
Other descriptive name: SACUBITRIL VALSARTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: the primary objective of this study is to evaluate the proportion of patients in the Pre- and Post-discharge treatment initiation groups achieving the target dose of 200 mg LCZ696 twice daily at the end of the week-10 after randomization (Treatment Epoch), regardless of previous temporary dose interruption or down-titration.

Secondary Objective: - To assess the proportion of patients that, regardless of previous dose interruption or downtitration during the Treatment Epoch, achieved and maintained either the dose of 100 mg
and/or 200 mg LCZ696 bid.
- To asssess the proportion of patients that, regardless of previous dose interruption or downtitration during the Treatment Epoch, achieved and maintained any dose of LCZ696.
- To assess the proportion of patients permanently discontinued from study drug, due to Adverse Events during the 10-week Treatment Epoch.

Primary end point(s): The proportion of patients who achieve 10 weeks up-titration success

Timepoint(s) of evaluation of this end point: 10 weeks after randomization

Secondary Outcome(s)

Secondary end point(s): - Assess the proportion of patients achieving and maintaining either the dose of 100 mg and/or 200 mg LCZ696 bid for at least 2 weeks leading to week 10 after randomization.
- Assess the proportion of patients achieving and maintaining any dose of LCZ696 for at least 2 weeks leading to week 10 after randomization.
- Assess the proportion of patients permanently discontinuation from study drug, at any time between randomization and week 10.

Timepoint(s) of evaluation of this end point: 10 weeks after randomization

Secondary ID(s)

CLCZ696B2401

Source(s) of Monetary Support

Novartis Pharma services AG

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 06/07/2019
• Date Completed: 20/06/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003266-87/results