Trial Outcomes & Findings for The Effects of Sacubitril/Valsartan Compared to Valsartan on LV Remodelling in Asymptomatic LV Systolic Dysfunction After MI (NCT NCT03552575)
NCT ID: NCT03552575
Last Updated: 2023-05-03
Results Overview
Change in indexed left ventricular end-systolic volume (LVESVI) measured by cardiac MR measured in ml/m2
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
93 participants
Primary outcome timeframe
baseline and 12 months
Results posted on
2023-05-03
Participant Flow
Participant milestones
| Measure |
Sacubitril/Valsartan
24mg/26mg, 49mg/51mg and 97mg/103mg twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. Used in line with SmPC guidelines. Following randomization the aim should be to up-titrate patients to target study drug dose 97/103mg twice daily after 4 weeks . Slower up-titration was permitted if necessary to ensure patient safety and tolerability. Patients will be allowed to stay at dose level 1 or 2 as maintenance dose however efforts should be made to maintain patients on the target dose level 3 or maximally tolerated dose level for as long a duration as possible during the trial. Adjustments to study drug dose level should be based on safety and tolerability with a focus on a) symptomatic hypotension, b) clinically significant decline in renal function and c) hyperkalaemia.
|
Valsartan
40mg, 80mg and 160mg twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor. Used within SmPC guidelines. Following randomization the aim should be to up-titrate patients to target study drug dose 160mg twice daily after 4 weeks . Slower up-titration was permitted if necessary to ensure patient safety and tolerability. Patients will be allowed to stay at dose level 1 or 2 as maintenance dose however efforts should be made to maintain patients on the target dose level 3 or maximally tolerated dose level for as long a duration as possible during the trial. Adjustments to study drug dose level should be based on safety and tolerability with a focus on a) symptomatic hypotension, b) clinically significant decline in renal function and c) hyperkalaemia.
|
|---|---|---|
|
Overall Study
STARTED
|
47
|
46
|
|
Overall Study
COMPLETED
|
46
|
46
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Effects of Sacubitril/Valsartan Compared to Valsartan on LV Remodelling in Asymptomatic LV Systolic Dysfunction After MI
Baseline characteristics by cohort
| Measure |
Sacubitril/Valsartan
n=47 Participants
24mg/26mg (dose level 1), 49mg/51mg (dose level 2) and 97mg/103mg (dose level 3) twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=46 Participants
40mg (dose level 1), 80mg (dose level 2) and 160mg (dose level 3) twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
Total
n=93 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
26 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
57 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
21 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
36 Participants
n=206 Participants
|
|
Age, Continuous
|
61.8 years
STANDARD_DEVIATION 10.6 • n=99 Participants
|
59.7 years
STANDARD_DEVIATION 10.1 • n=107 Participants
|
60.7 years
STANDARD_DEVIATION 10.4 • n=206 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=99 Participants
|
43 Participants
n=107 Participants
|
85 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
47 Participants
n=99 Participants
|
44 Participants
n=107 Participants
|
91 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United Kingdom
|
47 participants
n=99 Participants
|
46 participants
n=107 Participants
|
93 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: baseline and 12 monthsPopulation: There were 3 patients with incomplete data (1 death and 2 did not tolerate the MRI scan) accounting for the difference in overall number of participants randomised to those analyzed.
Change in indexed left ventricular end-systolic volume (LVESVI) measured by cardiac MR measured in ml/m2
Outcome measures
| Measure |
Sacubitril/Valsartan
n=46 Participants
24mg/26mg , 49mg/51mg and 97mg/103mg twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=44 Participants
40mg , 80mg and 160mg twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
|---|---|---|
|
Change in Left Ventricular End Systolic Volume Index
|
-4.0 ml/m^2
Standard Deviation 6.6
|
-2.0 ml/m^2
Standard Deviation 7.3
|
SECONDARY outcome
Timeframe: baseline and 12 monthsmeasured in pg/ml
Outcome measures
| Measure |
Sacubitril/Valsartan
n=46 Participants
24mg/26mg , 49mg/51mg and 97mg/103mg twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=46 Participants
40mg , 80mg and 160mg twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
|---|---|---|
|
Change in N-terminal Prohormone of B-type Natriuretic Peptide Levels
|
-39 pg/mL
Interval -131.0 to 12.0
|
-21 pg/mL
Interval -104.0 to 23.0
|
SECONDARY outcome
Timeframe: baseline and 12 monthsmeasured in ng/L
Outcome measures
| Measure |
Sacubitril/Valsartan
n=46 Participants
24mg/26mg , 49mg/51mg and 97mg/103mg twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=46 Participants
40mg , 80mg and 160mg twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
|---|---|---|
|
Change in High Sensitivity Troponin I Levels
|
-1.1 ng/L
Interval -2.4 to -0.1
|
-0.4 ng/L
Interval -2.4 to 0.9
|
SECONDARY outcome
Timeframe: baseline and 12 monthsChange in indexed left ventricular end-diastolic volume (LVEDVI) measured by cardiac MR measured in ml/m2
Outcome measures
| Measure |
Sacubitril/Valsartan
n=46 Participants
24mg/26mg , 49mg/51mg and 97mg/103mg twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=44 Participants
40mg , 80mg and 160mg twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
|---|---|---|
|
Change in Left Ventricular End-Diastolic Volume Index
|
-4.4 ml/m^2
Standard Deviation 8.8
|
-1.2 ml/m^2
Standard Deviation 8.6
|
SECONDARY outcome
Timeframe: baseline and 12 monthsChange in indexed Left Atrial Volume (LAVI) measured by cardiac MR measured in ml/m2
Outcome measures
| Measure |
Sacubitril/Valsartan
n=46 Participants
24mg/26mg , 49mg/51mg and 97mg/103mg twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=43 Participants
40mg , 80mg and 160mg twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
|---|---|---|
|
Change in Left Atrial Volume Index
|
-2.8 ml/m^2
Standard Deviation 9.0
|
-0.8 ml/m^2
Standard Deviation 11.7
|
SECONDARY outcome
Timeframe: baseline and 12 monthsChange in left ventricular ejection fraction (LVEF) measured by cardiac MR measured in percentage
Outcome measures
| Measure |
Sacubitril/Valsartan
n=46 Participants
24mg/26mg , 49mg/51mg and 97mg/103mg twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=44 Participants
40mg , 80mg and 160mg twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
|---|---|---|
|
Change in Left Ventricular Ejection Fraction
|
1.1 Ejection fraction %
Standard Deviation 3.4
|
1.4 Ejection fraction %
Standard Deviation 3.6
|
SECONDARY outcome
Timeframe: baseline and 12 monthsChange in indexed left ventricular mass (LVMI) measured by cardiac MR measured in grams/m2
Outcome measures
| Measure |
Sacubitril/Valsartan
n=46 Participants
24mg/26mg , 49mg/51mg and 97mg/103mg twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=44 Participants
40mg , 80mg and 160mg twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
|---|---|---|
|
Change in Left Ventricular Mass Index
|
-2.4 g/m^2
Standard Deviation 4.9
|
-1.1 g/m^2
Standard Deviation 5.0
|
SECONDARY outcome
Timeframe: 12 monthsChange in patient well being as assessed by patient global assessment questionnaire which is a patient reported outcome measure that involves a patients own response to questions about their overall health and/or disease activity
Outcome measures
| Measure |
Sacubitril/Valsartan
n=46 Participants
24mg/26mg , 49mg/51mg and 97mg/103mg twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=46 Participants
40mg , 80mg and 160mg twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
|---|---|---|
|
Change in Patient Well Being as Assessed by Patient Global Assessment Questionnaire
Slightly worsened
|
0 Participants
|
0 Participants
|
|
Change in Patient Well Being as Assessed by Patient Global Assessment Questionnaire
Moderately worsened
|
0 Participants
|
0 Participants
|
|
Change in Patient Well Being as Assessed by Patient Global Assessment Questionnaire
Markedly improved
|
8 Participants
|
8 Participants
|
|
Change in Patient Well Being as Assessed by Patient Global Assessment Questionnaire
Moderately improved
|
9 Participants
|
7 Participants
|
|
Change in Patient Well Being as Assessed by Patient Global Assessment Questionnaire
Slightly improved
|
5 Participants
|
10 Participants
|
|
Change in Patient Well Being as Assessed by Patient Global Assessment Questionnaire
Unchanged
|
24 Participants
|
21 Participants
|
|
Change in Patient Well Being as Assessed by Patient Global Assessment Questionnaire
Markedly worsened
|
0 Participants
|
0 Participants
|
Adverse Events
Sacubitril/Valsartan
Serious events: 8 serious events
Other events: 12 other events
Deaths: 1 deaths
Valsartan
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sacubitril/Valsartan
n=47 participants at risk
24mg/26mg (dose level 1), 49mg/51mg (dose level 2) and 97mg/103mg (dose level 3) twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=46 participants at risk
40mg (dose level 1), 80mg (dose level 2) and 160mg (dose level 3) twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
2.1%
1/47 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
2.2%
1/46 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
2.1%
1/47 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Gastrointestinal disorders
Pancreatitis
|
2.1%
1/47 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
General disorders
Sudden death
|
2.1%
1/47 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Infections and infestations
Influenza
|
2.1%
1/47 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Infections and infestations
Sepsis
|
2.1%
1/47 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Injury, poisoning and procedural complications
Procedural hypotension
|
2.1%
1/47 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
2.1%
1/47 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Nervous system disorders
Cerebral infarction
|
2.1%
1/47 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
Other adverse events
| Measure |
Sacubitril/Valsartan
n=47 participants at risk
24mg/26mg (dose level 1), 49mg/51mg (dose level 2) and 97mg/103mg (dose level 3) twice daily
sacubitril/valsartan: Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
|
Valsartan
n=46 participants at risk
40mg (dose level 1), 80mg (dose level 2) and 160mg (dose level 3) twice daily.
Valsartan: is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor.
|
|---|---|---|
|
Renal and urinary disorders
Worsening renal function or acute kidney injury
|
10.6%
5/47 • Number of events 5 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
8.7%
4/46 • Number of events 4 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Renal and urinary disorders
Hyperkalaemia
|
4.3%
2/47 • Number of events 3 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
2.2%
1/46 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Cardiac disorders
Symptomatic hypotension
|
14.9%
7/47 • Number of events 8 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
2.2%
1/46 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Blood and lymphatic system disorders
Symptomatic hypotension with systolic blood pressure <90mmHg
|
2.1%
1/47 • Number of events 1 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Immune system disorders
Angioedema
|
0.00%
0/47 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/47 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
0.00%
0/46 • 1 year of study follow up whilst taking study drug and an additional 30 days following the final study visit.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place