Question 14- Prove Trial

Question 1

Study Characteristics

Answer 1

• conducted to determine weather changes in NT-proBNP correlate w/changes in measures of cardiac structure, volume, and function in patients w/HFrEF treated with sacubtril valsartan
• They wanted to help gain a greater understanding of the clinical impact of Entresto as demonstrated in paradigm and pioneer.

Question 2

Primary End Points

Answer 2

Correlation between changes in NT-proBNP and cardiac remodeling, as assessed by cardiac structure remodeling parameters from baseline to 12 months.

Question 3

Secondary End Points

Answer 3

Correlation between change in NT-proBNP and cardiac remodeling as assessed by cardiac structure remodeling parameters from baseline to 6 months.

Question 4

Inclusion Criteria

Answer 4

• They studied 794 adult patients with left ventricular ejection fraction below 40% NYHA Class II-IV (2-4)
• If patient was on a loop diuretic they had to be stable for 2 weeks.

Question 5

Exclusion Criteria

Answer 5

History of hypersensitivity to any study-drug component or to drugs of similar classes, history of angioedema, use of an ACE inhibitor, and elevated potassium at screening.

Question 6

Study Design

Answer 6

• Conducted between October 2016-2018
• 12 month, single-group, open-label study in patients with HFrEF in 78 outpatient sites in the US.
• Patients on ACEis and ARBS had to discontinue their usage and were given sacubitril valsartan.
• Their dose would increase approx. every 2 weeks through the first 60 days until maximum dose of 97/103mg twice daily was achieved.
• If any unacceptable adverse events were reported, patients were able to discontinue.
• At each visit, a sample of blood was taken and studied to measure plasma NT-proBNP.
• An echocardiography test was also done on patients after enrollment, at 6 months, and then again at 12 months following completion of all study procedures to interpret results.

Question 7

Patient Characteristics

Answer 7

-794 male and female patients participated
-Patients with NHYA Class II-IV (2-4) symptoms were studied, with majority being Class 2
-Race
o White-73%
o Black- 23%
o Asian- 0.8%
o Other- 3.2%
-Majority of patients had previously been on an ACEi or ARB, but weren’t on them at the time of the study.

Question 8

Safety

Answer 8

• No new safety concerns were discovered. Safety profile was consistent with the Paradigm and Pioneer tirals
• Adverse events
• Hypotension, dizziness, hyperkalemia, and worsening kidney function
• Low reports of angioedema. It only occurred in 2 patients.

Question 9

Efficacy

Answer 9

• Initiation and titration of sacubitril valsartan was associated with a reduction in NT-proBNP concentration, with evident reduction occurring 2 weeks after initiation.
• By day 14, there was a 30% reduction in NT-proBNP, by 6 months there as a 35% reduction, and by 12 months reduction was at 37%.

Question 10

Benefits

Answer 10

It was proven that Entresto can improve changes in measures of NT-proBNP with patients who suffer from HFrEF. Because of that, patients may also see improvements in cardiac structure and function.