A Phase 4 interventional study of sacubitril/valsatran and valsartan in Heart Failure, sponsored by Novartis Pharmaceuticals. Completed at 1 site in Finland. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-01-05.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 4, Interventional, and Treatment
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.
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.
6,331 studies on the registry are indexed under Heart Failure; 1,396 are open to participants now.
This study's enrollment of 55 is below the median of 76 across 4,049 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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).
Drug: sacubitril/valsatran · Drug: placebo to 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)
Drug: valsartan · Drug: placebo to sacubitril/valsartan
sacubitril/valsatran 100 or 200 mg BID
Valsartan 80 or 160 mg BID
placebo to valsartan 80 or 160 BID
placebo to sacubitril/valsartan 100 or 200 mg BID
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Visit 3 (approximately Week 8)
| Milestone | Sacubitril/Valsartan | Valsartan |
|---|---|---|
| Started | 27 | 28 |
| Completed | 27 | 28 |
| Not completed | 0 | 0 |
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.
| (((mmhg x ml x bpm) /g)/(1/min)) | Sacubitril/Valsartan | Valsartan |
|---|---|---|
| Baseline (Day 1) | 48621.3 ± 17001.4 | 50035.7 ± 18068.2 |
| Visit 3 | 50301.0 ± 20842.7 | 52942.8 ± 19702.5 |
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.
| (((mmhg x ml x bpm) /g)/(1/min)) | Sacubitril/Valsartan | Valsartan |
|---|---|---|
| Change From Baseline in Myocardial Energetic Efficiency | 1679.8 ± 9282.4 | 2907.1 ± 11571.5 |
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.
| (((mmhg x ml x bpm) /g)/(1/min)) | Sacubitril/Valsartan | Valsartan |
|---|---|---|
| Baseline | 48163.0 ± 16719.8 | 49575.6 ± 18255.8 |
| Visit 3 | 49914.4 ± 20821.2 | 52249.9 ± 19585.8 |
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.
| (((mmhg x ml x bpm) /g)/(1/min)) | Sacubitril/Valsartan | Valsartan |
|---|---|---|
| Change From Baseline in Viable Myocardial Energetic Efficiency (Sensitivity Analysis) | 1751.4 ± 9098.1 | 2674.3 ± 11551.2 |
Collected over 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.. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Sacubitril/Valsartan | 0/27 (0%) | 1/27 (3.7%) | 4/27 (14.8%) |
| Valsartan | 0/28 (0%) | 0/28 (0%) | 5/28 (17.9%) |
| Event | Sacubitril/Valsartan | Valsartan |
|---|---|---|
| Cerebrovascular accidentNervous system disorders | 1/27 | 0/28 |
| Event | Sacubitril/Valsartan | Valsartan |
|---|---|---|
| DizzinessNervous system disorders | 2/27 | 1/28 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/27 | 0/28 |
| PruritusSkin and subcutaneous tissue disorders | 1/27 | 0/28 |
| NauseaGastrointestinal disorders | 0/27 | 1/28 |
| FatigueGeneral disorders | 0/27 | 1/28 |
| Blood potassium increasedInvestigations | 0/27 | 1/28 |
| HeadacheNervous system disorders | 0/27 | 1/28 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/27 | 1/28 |
| Age, Continuous(years) | Sacubitril/Valsartan | Valsartan | Total |
|---|---|---|---|
| Mean | 63.1 ± 10.1 | 64.4 ± 7.5 | 63.8 ± 8.8 |
| Sex: Female, Male(Participants) | Sacubitril/Valsartan | Valsartan | Total |
|---|---|---|---|
| Female | 5 | 7 | 12 |
| Male | 22 | 21 | 43 |
| Race/Ethnicity, Customized(Participants) | Sacubitril/Valsartan | Valsartan | Total |
|---|---|---|---|
| White | 27 | 28 | 55 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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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