Heart FailurePhase 4TurkuPETNCT03300427

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

A Phase 4 study testing sacubitril/valsatran and valsartan in people with Heart Failure, run by Novartis Pharmaceuticals at 1 site in Finland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 40 to 80 years
Conditions the study is for: Heart Failure
What is being tested?: sacubitril/valsatran and valsartan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 55 participants
Where: 1 siteFinland
Study dates: 5 Jul 2018to 23 Mar 2022
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Finland1 site

Novartis Investigative Site
Turku, 20521

Other trials in Finland

About this study

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

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.

Read the 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
Being tested: sacubitril/valsatran, valsartan, placebo to valsartan, placebo to sacubitril/valsartan
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
Medical subject headings: Heart Failure, Dilatation, Pathologic, Hypertrophy, Left Ventricular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

sacubitril/valsatranDrug
sacubitril/valsatran 100 or 200 mg BID
valsartanDrug
Valsartan 80 or 160 mg BID
placebo to valsartanDrug
placebo to valsartan 80 or 160 BID
placebo to sacubitril/valsartanDrug
placebo to sacubitril/valsartan 100 or 200 mg BID

Study groups in NCT03300427
Study group	Role	What they receive
sacubitril/valsartan	Experimental	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). Receives: Drug: sacubitril/valsatran; Drug: placebo to valsartan
valsartan	Active comparator	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) Receives: Drug: valsartan; Drug: placebo to sacubitril/valsartan

What is being measured

The primary outcome is the main question the study is designed to answer.

Myocardial Energetic Efficiency
Positron emission tomography (PET) imaging and echocardiography were performed before randomization (after a minimum of 4 weeks on stable dose of 80 mg BID or 160 mg BID of valsartan) and repeated after 6 weeks on a stable dose of either 80 mg BID or 160 mg BID of valsartan or 100 mg BID or 200 mg BID of sacubitril/valsartan.
Cardiac efficiency was calculated based on the following formula: Myocardial efficiency = ((SBP x SV x HR)/LV mass)/Kmono Where
- SBP : Systolic blood pressure during PET
- SV : Stroke volume (Echocardiography)
- HR : Heart rate
- Kmono: Mono-exponential clearance rate (11C-acetate PET- scan)
- LV mass: Left ventricular mass
Visit 3 was performed after the study treatment was on a stable dose for a minimum of 6 weeks. It could be performed before or after 8 weeks, based on when the last dose modification was performed.
No imputation of missing data was performed.
Measured: Baseline, Visit 3 (approximately Week 8)
Change From Baseline in Myocardial Energetic Efficiency
Positron emission tomography (PET) imaging and echocardiography were performed before randomization (after a minimum of 4 weeks on stable dose of 80 mg BID or 160 mg BID of valsartan) and repeated after 6 weeks on a stable dose of either 80 mg BID or 160 mg BID of valsartan or 100 mg BID or 200 mg BID of sacubitril/valsartan.
Cardiac efficiency was calculated based on the following formula: Myocardial efficiency = ((SBP x SV x HR)/LV mass)/Kmono Where
- SBP : Systolic blood pressure during PET
- SV : Stroke volume (Echocardiography)
- HR : Heart rate
- Kmono: Mono-exponential clearance rate (11C-acetate PET- scan)
- LV mass: Left ventricular mass
Visit 3 was performed after the study treatment was on a stable dose for a minimum of 6 weeks. It could be performed before or after 8 weeks, based on when the last dose modification was performed.
No imputation of missing data was performed.
Measured: Baseline, Visit 3 (approximately Week 8)
Viable Myocardial Energetic Efficiency (Sensitivity Analysis)
In addition to the derivation of the primary endpoint, an alternative formula was used, where the viable myocardial energetic efficiency was derived as:
Viable myocardial energetic efficiency = ((SBP x SV x HR)/LV mass) / vKmono Where vKmono is the viable myocardium clearance rate. This alternative parameter was included as a sensitivity analysis to exclude possible bias related to scar tissue in patients with ischemic myopathy.
Measured: Baseline, Visit 3 (approximately Week 8)
Change From Baseline in Viable Myocardial Energetic Efficiency (Sensitivity Analysis)
In addition to the derivation of the primary endpoint, an alternative formula was used, where the viable myocardial energetic efficiency was derived as:
Viable myocardial energetic efficiency = ((SBP x SV x HR)/LV mass) / vKmono Where vKmono is the viable myocardium clearance rate. This alternative parameter was included as a sensitivity analysis to exclude possible bias related to scar tissue in patients with ischemic myopathy.
Measured: Baseline, Visit 3 (approximately Week 8)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Jul 201823 Mar 2022

First posted3 Oct 2017
Study start5 Jul 2018
Primary completion23 Mar 2022
Study completion23 Mar 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Heart FailureStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 55 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03300427
Sponsor's protocol ID: CLCZ696BFI03
Other IDs: 2017-002113-64, 2017
Acronym: TurkuPET
Status last verified: Mar 2023
First submitted: 28 Sep 2017
Last updated: 5 Jan 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
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Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
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Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic

All Heart Failure trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03300427
Acronym / sponsor ID: TurkuPET / CLCZ696BFI03
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
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 55 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 5 Jul 2018 (actual)
Primary completion: 23 Mar 2022 (actual)
Study completion: 23 Mar 2022 (actual)
First posted: 3 Oct 2017 (actual)
Results: Posted 5 Jan 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
sacubitril/valsartan	Experimental	Drug: sacubitril/valsatran, Drug: placebo to valsartansubjects 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).
valsartan	Active comparator	Drug: valsartan, Drug: placebo to sacubitril/valsartansubjects 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)

Who may qualify

Ages: 40 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (2 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
sacubitril/valsatransacubitril/valsatran 100 or 200 mg BID	Drug	sacubitril/valsartan
valsartanValsartan 80 or 160 mg BID	Drug	valsartan
placebo to valsartanplacebo to valsartan 80 or 160 BID	Drug	sacubitril/valsartan
placebo to sacubitril/valsartanplacebo to sacubitril/valsartan 100 or 200 mg BID	Drug	valsartan

Primary outcome

Myocardial Energetic Efficiency
Time frame: Baseline, Visit 3 (approximately Week 8)
Positron emission tomography (PET) imaging and echocardiography were performed before randomization (after a minimum of 4 weeks on stable dose of 80 mg BID or 160 mg BID of valsartan) and repeated after 6 weeks on a stable dose of either 80 mg BID or 160 mg BID of valsartan or 100 mg BID or 200 mg BID of sacubitril/valsartan. Cardiac efficiency was calculated based on the following formula: Myocardial efficiency = ((SBP x SV x HR)/LV mass)/Kmono Where * SBP : Systolic blood pressure during PET * SV : Stroke volume (Echocardiography) * HR : Heart rate * Kmono: Mono-exponential clearance rate (11C-acetate PET- scan) * LV mass: Left ventricular mass Visit 3 was performed after the study treatment was on a stable dose for a minimum of 6 weeks. It could be performed before or after 8 weeks, based on when the last dose modification was performed. No imputation of missing data was performed.
Change From Baseline in Myocardial Energetic Efficiency
Time frame: Baseline, Visit 3 (approximately Week 8)
Positron emission tomography (PET) imaging and echocardiography were performed before randomization (after a minimum of 4 weeks on stable dose of 80 mg BID or 160 mg BID of valsartan) and repeated after 6 weeks on a stable dose of either 80 mg BID or 160 mg BID of valsartan or 100 mg BID or 200 mg BID of sacubitril/valsartan. Cardiac efficiency was calculated based on the following formula: Myocardial efficiency = ((SBP x SV x HR)/LV mass)/Kmono Where * SBP : Systolic blood pressure during PET * SV : Stroke volume (Echocardiography) * HR : Heart rate * Kmono: Mono-exponential clearance rate (11C-acetate PET- scan) * LV mass: Left ventricular mass Visit 3 was performed after the study treatment was on a stable dose for a minimum of 6 weeks. It could be performed before or after 8 weeks, based on when the last dose modification was performed. No imputation of missing data was performed.
Viable Myocardial Energetic Efficiency (Sensitivity Analysis)
Time frame: Baseline, Visit 3 (approximately Week 8)
In addition to the derivation of the primary endpoint, an alternative formula was used, where the viable myocardial energetic efficiency was derived as: Viable myocardial energetic efficiency = ((SBP x SV x HR)/LV mass) / vKmono Where vKmono is the viable myocardium clearance rate. This alternative parameter was included as a sensitivity analysis to exclude possible bias related to scar tissue in patients with ischemic myopathy.
Change From Baseline in Viable Myocardial Energetic Efficiency (Sensitivity Analysis)
Time frame: Baseline, Visit 3 (approximately Week 8)
In addition to the derivation of the primary endpoint, an alternative formula was used, where the viable myocardial energetic efficiency was derived as: Viable myocardial energetic efficiency = ((SBP x SV x HR)/LV mass) / vKmono Where vKmono is the viable myocardium clearance rate. This alternative parameter was included as a sensitivity analysis to exclude possible bias related to scar tissue in patients with ischemic myopathy.

Results and safety

Results posted to the registry on 5 Jan 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sacubitril/Valsartan	27	27
Valsartan	28	28

Primary outcome: Myocardial Energetic Efficiency

Time frame: Baseline, Visit 3 (approximately Week 8). Mean (Standard Deviation). Unit: (((mmhg x ml x bpm) /g)/(1/min))

Measure	Sacubitril/Valsartan n = 27	Valsartan n = 28
Baseline (Day 1)	48621.3 (17001.4)	50035.7 (18068.2)
Visit 3	50301.0 (20842.7)	52942.8 (19702.5)

Population analysed: Full analysis set (FAS): consisted of all randomized patients who had received at least one dose of study medication in the treatment period and had at least one post-baseline assessment of any efficacy endpoints.

Primary outcome: Change From Baseline in Myocardial Energetic Efficiency

Time frame: Baseline, Visit 3 (approximately Week 8). Mean (Standard Deviation). Unit: (((mmhg x ml x bpm) /g)/(1/min))

Measure	Sacubitril/Valsartan n = 27	Valsartan n = 28
Value	1679.8 (9282.4)	2907.1 (11571.5)

Sacubitril/Valsartan vs Valsartan: difference in least square means: -900.0 (95% CI -6781.7 to 4981.8), p = 0.7594, ANCOVA

Primary outcome: Viable Myocardial Energetic Efficiency (Sensitivity Analysis)

Time frame: Baseline, Visit 3 (approximately Week 8). Mean (Standard Deviation). Unit: (((mmhg x ml x bpm) /g)/(1/min))

Measure	Sacubitril/Valsartan n = 27	Valsartan n = 28
Baseline	48163.0 (16719.8)	49575.6 (18255.8)
Visit 3	49914.4 (20821.2)	52249.9 (19585.8)

Primary outcome: Change From Baseline in Viable Myocardial Energetic Efficiency (Sensitivity Analysis)

Time frame: Baseline, Visit 3 (approximately Week 8). Mean (Standard Deviation). Unit: (((mmhg x ml x bpm) /g)/(1/min))

Measure	Sacubitril/Valsartan n = 27	Valsartan n = 28
Value	1751.4 (9098.1)	2674.3 (11551.2)

Sacubitril/Valsartan vs Valsartan: difference in least square means: -575.5 (95% CI -6365.5 to 5214.5), p = 0.8422, ANCOVA

Adverse events

Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 86 days.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sacubitril/Valsartan	1 of 27 (3.7%)	4 of 27 (14.8%)	0 of 27
Valsartan	0 of 28 (0%)	5 of 28 (17.9%)	0 of 28

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing sacubitril/valsatran and valsartan in people with Heart Failure, run by Novartis Pharmaceuticals at 1 site in Finland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Myocardial Energetic Efficiency (time frame: Baseline, Visit 3 (approximately Week 8)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03300427.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2024.