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

Novartis

Status and phase: Completed; Phase 4

Conditions: Heart Failure

Treatments: Drug: placebo to valsartan; Drug: sacubitril/valsatran; Drug: valsartan; Drug: placebo to sacubitril/valsartan

Study type: Interventional

Funder types: Industry

Identifiers

NCT03300427

CLCZ696BFI03

2017-002113-64 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 55 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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55 participants in 2 patient groups

sacubitril/valsartan

Experimental group

Description:

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).

Treatment:

Drug: placebo to valsartan

Drug: sacubitril/valsatran

valsartan

Active Comparator group

Description:

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)

Treatment:

Drug: valsartan

Drug: placebo to sacubitril/valsartan