Trial Outcomes & Findings for The Effects of Sacubitril/Valsartan on Cardiac Oxygen Consumption and Efficiency of Cardiac Work in Heart Failure Patients (NCT NCT03300427)
NCT ID: NCT03300427
Last Updated: 2024-01-05
Results Overview
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.
COMPLETED
PHASE4
55 participants
Baseline, Visit 3 (approximately Week 8)
2024-01-05
Participant Flow
The patients who signed the ICF entered the screening/run-in period of the study. After the screening evaluations and confirmation of eligibility, the patients were allocated randomization numbers and randomized to receive the treatment assigned to each number in a blinded manner.
Participant milestones
| Measure |
Sacubitril/Valsartan
subjects receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose is then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible).
|
Valsartan
subjects receive 80 mg orally twice daily (BID). The dose is then up-titrated to 160 mg BID (or maintained at the starting level, if up-titration is not possible)
|
|---|---|---|
|
Overall Study
STARTED
|
27
|
28
|
|
Overall Study
COMPLETED
|
27
|
28
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Effects of Sacubitril/Valsartan on Cardiac Oxygen Consumption and Efficiency of Cardiac Work in Heart Failure Patients
Baseline characteristics by cohort
| Measure |
Sacubitril/Valsartan
n=27 Participants
subjects receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose is then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible).
|
Valsartan
n=28 Participants
subjects receive 80 mg orally twice daily (BID). The dose is then up-titrated to 160 mg BID (or maintained at the starting level, if up-titration is not possible)
|
Total
n=55 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.1 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
64.4 years
STANDARD_DEVIATION 7.5 • n=7 Participants
|
63.8 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
27 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Visit 3 (approximately Week 8)Population: 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.
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.
Outcome measures
| Measure |
Sacubitril/Valsartan
n=27 Participants
subjects receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose is then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible).
|
Valsartan
n=28 Participants
subjects receive 80 mg orally twice daily (BID). The dose is then up-titrated to 160 mg BID (or maintained at the starting level, if up-titration is not possible)
|
|---|---|---|
|
Myocardial Energetic Efficiency
Baseline (Day 1)
|
48621.3 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 17001.4
|
50035.7 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 18068.2
|
|
Myocardial Energetic Efficiency
Visit 3
|
50301.0 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 20842.7
|
52942.8 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 19702.5
|
PRIMARY outcome
Timeframe: Baseline, Visit 3 (approximately Week 8)Population: 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.
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.
Outcome measures
| Measure |
Sacubitril/Valsartan
n=27 Participants
subjects receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose is then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible).
|
Valsartan
n=28 Participants
subjects receive 80 mg orally twice daily (BID). The dose is then up-titrated to 160 mg BID (or maintained at the starting level, if up-titration is not possible)
|
|---|---|---|
|
Change From Baseline in Myocardial Energetic Efficiency
|
1679.8 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 9282.4
|
2907.1 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 11571.5
|
PRIMARY outcome
Timeframe: Baseline, Visit 3 (approximately Week 8)Population: 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.
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.
Outcome measures
| Measure |
Sacubitril/Valsartan
n=27 Participants
subjects receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose is then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible).
|
Valsartan
n=28 Participants
subjects receive 80 mg orally twice daily (BID). The dose is then up-titrated to 160 mg BID (or maintained at the starting level, if up-titration is not possible)
|
|---|---|---|
|
Viable Myocardial Energetic Efficiency (Sensitivity Analysis)
Baseline
|
48163.0 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 16719.8
|
49575.6 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 18255.8
|
|
Viable Myocardial Energetic Efficiency (Sensitivity Analysis)
Visit 3
|
49914.4 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 20821.2
|
52249.9 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 19585.8
|
PRIMARY outcome
Timeframe: Baseline, Visit 3 (approximately Week 8)Population: 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.
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.
Outcome measures
| Measure |
Sacubitril/Valsartan
n=27 Participants
subjects receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose is then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible).
|
Valsartan
n=28 Participants
subjects receive 80 mg orally twice daily (BID). The dose is then up-titrated to 160 mg BID (or maintained at the starting level, if up-titration is not possible)
|
|---|---|---|
|
Change From Baseline in Viable Myocardial Energetic Efficiency (Sensitivity Analysis)
|
1751.4 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 9098.1
|
2674.3 (((mmhg x ml x bpm) /g)/(1/min))
Standard Deviation 11551.2
|
Adverse Events
Sacubitril/Valsartan
Valsartan
Serious adverse events
| Measure |
Sacubitril/Valsartan
n=27 participants at risk
subjects receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose is then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible).
|
Valsartan
n=28 participants at risk
subjects receive 80 mg orally twice daily (BID). The dose is then up-titrated to 160 mg BID (or maintained at the starting level, if up-titration is not possible)
|
|---|---|---|
|
Nervous system disorders
Cerebrovascular accident
|
3.7%
1/27 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
0.00%
0/28 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
Other adverse events
| Measure |
Sacubitril/Valsartan
n=27 participants at risk
subjects receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose is then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible).
|
Valsartan
n=28 participants at risk
subjects receive 80 mg orally twice daily (BID). The dose is then up-titrated to 160 mg BID (or maintained at the starting level, if up-titration is not possible)
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/27 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
3.6%
1/28 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
|
General disorders
Fatigue
|
0.00%
0/27 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
3.6%
1/28 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
|
Investigations
Blood potassium increased
|
0.00%
0/27 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
3.6%
1/28 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
|
Nervous system disorders
Dizziness
|
7.4%
2/27 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
3.6%
1/28 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
|
Nervous system disorders
Headache
|
0.00%
0/27 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
3.6%
1/28 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.7%
1/27 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
0.00%
0/28 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/27 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
3.6%
1/28 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.7%
1/27 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
0.00%
0/28 • 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.
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination findings, laboratory test findings, or other assessments.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER