Clinical trial NCT03300427: The Effects of Sacubitril/Valsartan on Cardiac Oxygen Consumption and Efficiency of Cardiac Work in Heart Failure Patients
Official title: Controlled Trial on the Short-term Effects of Sacubitril/Valsartan Therapy on Cardiac Oxygen Consumption and Efficiency of Cardiac Work in Patients With NYHA II-III Heart Failure and Reduced Systolic Function Using 11C-acetate Positron Emission Tomography and Echocardiography
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Keywords: Heart failure with reduced left ventricular ejection fraction
LVEF
Cardiac dysfunction
Heart muscle dysfunction
Left ventricular (LV) dilation
Left ventricular hypertrophy
HF
AHF
CHF
CCF
acute heart failure
chronic heart failure
congestive heart failure
congestive cardiac failure
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-10-03
Enrollment: 55
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Myocardial Energetic Efficiency
timeFrame: Baseline, Visit 3 (approximately Week 8)
measure: Change From Baseline in Myocardial Energetic Efficiency
timeFrame: Baseline, Visit 3 (approximately Week 8)
measure: Viable Myocardial Energetic Efficiency (Sensitivity Analysis)
timeFrame: Baseline, Visit 3 (approximately Week 8)
measure: Change From Baseline in Viable Myocardial Energetic Efficiency (Sensitivity Analysis)
timeFrame: Baseline, Visit 3 (approximately Week 8)
Secondary outcomes:
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Novartis Investigative Site
Study officials:
References: