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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03300427

Collaborator

(none)

Enrollment

Location

Arms

53.4

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study will assess the effects of 6 weeks of stable sacubitril/valsartan therapy, as compared with valsartan therapy, on cardiac oxygen consumption and 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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: sacubitril/valsatran Drug: valsartan Drug: placebo to valsartan Drug: placebo to sacubitril/valsartan	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 5, 2018

Anticipated Primary Completion Date :

Sep 16, 2022

Anticipated Study Completion Date :

Dec 16, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: sacubitril/valsartan Participants will be randomized to two treatment arms in a 1:1, double blinded fashion. Two strengths of sacubitril/valsartan will be available for use after randomization, 49 mg sacubitril/51 mg valsartan and 97 mg sacubitril/103 mg valsartan. After randomization, subjects in this arm will receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose will be then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible). Dose modifications are allowed until week 4 after the randomization. In order to be eligible for the final assessments, the subject has to tolerate the 100 mg BID dose at the minimum. In total, participants will be on sacubitril/valsartan for a minimum of 8 weeks and a maximum of 10 weeks.	Drug: sacubitril/valsatran sacubitril/valsatran 100 or 200 mg BID Drug: placebo to valsartan placebo to valsartan 80 or 160 BID
Active Comparator: valsartan Participants will be randomized to two treatment arms in a 1:1, double blinded fashion. In this arm, Valsartan 80 mg and 160 mg will be used as comparative drug, taken orally BID at home. Depending on the screening/run-in dose the subjects in this arm will get either valsartan 80 mg BID or valsartan 160 mg BID. During the treatment period the dose of valsartan will be up-titrated to the highest tolerated dose (160 mg BID) or maintained at 80 mg BID if up-titration is not possible. Dose modifications are allowed until week 4 after the randomization. In order to be eligible for the final assessments, the subject has to tolerate at least 80 mg BID dose of valsartan. The treatment phase will be a minimum of 8 weeks, and a maximum of 10 weeks.	Drug: valsartan Valsartan 80 or 160 mg BID Drug: placebo to sacubitril/valsartan placebo to sacubitril/valsartan 100 or 200 mg BID

Arm

Intervention/Treatment

Experimental: sacubitril/valsartan

Participants will be randomized to two treatment arms in a 1:1, double blinded fashion. Two strengths of sacubitril/valsartan will be available for use after randomization, 49 mg sacubitril/51 mg valsartan and 97 mg sacubitril/103 mg valsartan. After randomization, subjects in this arm will receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose will be then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible). Dose modifications are allowed until week 4 after the randomization. In order to be eligible for the final assessments, the subject has to tolerate the 100 mg BID dose at the minimum. In total, participants will be on sacubitril/valsartan for a minimum of 8 weeks and a maximum of 10 weeks.

Drug: sacubitril/valsatran

sacubitril/valsatran 100 or 200 mg BID

Drug: placebo to valsartan

placebo to valsartan 80 or 160 BID

Active Comparator: valsartan

Participants will be randomized to two treatment arms in a 1:1, double blinded fashion. In this arm, Valsartan 80 mg and 160 mg will be used as comparative drug, taken orally BID at home. Depending on the screening/run-in dose the subjects in this arm will get either valsartan 80 mg BID or valsartan 160 mg BID. During the treatment period the dose of valsartan will be up-titrated to the highest tolerated dose (160 mg BID) or maintained at 80 mg BID if up-titration is not possible. Dose modifications are allowed until week 4 after the randomization. In order to be eligible for the final assessments, the subject has to tolerate at least 80 mg BID dose of valsartan. The treatment phase will be a minimum of 8 weeks, and a maximum of 10 weeks.

Drug: valsartan

Valsartan 80 or 160 mg BID

Drug: placebo to sacubitril/valsartan

placebo to sacubitril/valsartan 100 or 200 mg BID

Outcome Measures

Primary Outcome Measures

Change from baseline in cardiac oxygen consumption and efficiency of cardiac work [baseline, at week 6]
Change from baseline in cardiac oxygen consumption and efficiency of cardiac work after 6 weeks of stable sacubitril/valsartan therapy compared to that of in patients on valsartan therapy using 11C-acetate positron emission tomography (PET).

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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.