The Effects of Sacubitril/Valsartan on Cardiac Oxygen Consumption and Efficiency of Cardiac Work in Heart Failure Patients

NCT ID: NCT03300427

Last Updated: 2024-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-05
• Study Completion Date: 2022-03-23

Brief Summary

This is a phase IV, prospective, randomized, double-blind, double-dummy, parallel-group study.

The study assessed the effects of 6 weeks of stable sacubitril/valsartan therapy, as compared with valsartan therapy, on the efficiency of cardiac work in patients with NYHA II-III heart failure (HF) and reduced systolic function using 11C-acetate positron emission tomography (PET) and echocardiography.

Detailed Description

Subjects were randomized into valsartan or sacubitril/valsartan arms in a 1:1 ratio. Regardless of the treatment arm a subject is in, the study drug was up-titrated to the highest tolerated dose level during the scheduled study visits. The different strengths of the two study drugs were not identical in appearance so the possible dose modification(s) during the treatment period could not be performed in a blinded manner. Subjects started on valsartan 80 mg BID or sacubitril/valsartan 100 mg BID dose and there was only one scheduled up-titration visit after the randomization. Exception for this were the subjects that were on valsartan 160 mg BID dose during the run-in phase. These subjects were randomized directly to valsartan 160 mg BID or sacubitril/valsartan 100 mg BID. Subjects that were randomized to valsartan arm had similar visit after which they continued on the same dose. For subjects that were randomized from valsartan 160 mg BID to sacubitril/valsartan 100 mg BID the dose was up-titrated to 200 mg BID if clinically possible.

The total duration for each patient was planned to be about 14 weeks but could be longer if required for scheduling purposes . The longest participation, from signing of ICF until end of study, was 26 weeks.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

sacubitril/valsartan

subjects received sacubitril/valsartan 100 mg orally twice daily (BID). The dose was then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration was not possible).

Group Type: EXPERIMENTAL

sacubitril/valsatran

Intervention Type: DRUG

sacubitril/valsatran 100 or 200 mg BID

placebo to valsartan

Intervention Type: DRUG

placebo to valsartan 80 or 160 BID

valsartan

subjects received 80 mg orally twice daily (BID). The dose was then up-titrated to 160 mg BID (or maintained at the starting level, if up-titration was not possible)

Group Type: ACTIVE_COMPARATOR

valsartan

Intervention Type: DRUG

Valsartan 80 or 160 mg BID

placebo to sacubitril/valsartan

Intervention Type: DRUG

placebo to sacubitril/valsartan 100 or 200 mg BID

Interventions

sacubitril/valsatran

sacubitril/valsatran 100 or 200 mg BID

Intervention Type: DRUG

valsartan

Valsartan 80 or 160 mg BID

Intervention Type: DRUG

placebo to valsartan

placebo to valsartan 80 or 160 BID

Intervention Type: DRUG

placebo to sacubitril/valsartan

placebo to sacubitril/valsartan 100 or 200 mg BID

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 40-80 years of age
• Chronic HF with reduced EF (left ventricle EF 25-35%) and NYHA class II-III symptoms.
• Systolic BP 110-160 mm Hg
• Optimal standard HF therapy according to European Society of Cardiology (ESC) guidelines at a stable dose for at least 4 weeks before the screening visit.

Exclusion Criteria

• Estimated glomerular filtration rate (eGFR) < 45 ml/min
• Serum potassium > 5.2 mmol/l and creatinine >1.5 x ULN

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

Turku, , Finland

Countries

Finland

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-002113-64

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLCZ696BFI03

Identifier Type: -

Identifier Source: org_study_id