Trial Outcomes & Findings for Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan) (NCT NCT02788656)

NCT ID: NCT02788656

Last Updated: 2020-02-17

Results Overview

Change in mean PAP in group A versus group B

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 4 participants
• Primary outcome timeframe: Baseline, 6 weeks
• Results posted on: 2020-02-17

Participant Flow

Participant milestones

Measure	Group A Group A will receive sacubitril/valsartan + placebo for weeks 1-12. and then sacubitril/valsartan only for weeks 13-32. All subjects in Group A will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device).	Group B Group B will receive an Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin II Type 1 Receptor Blocker (ARB) + placebo for weeks 1-6 (depending on previous background therapy) and then switch to sacubitril/valsartan + placebo for weeks 7-12. Group B will then receive sacubitril/valsartan only for weeks 13-32. All subjects in Group B will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device).
Overall Study STARTED	2	2
Overall Study COMPLETED	1	2
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Group A Group A will receive sacubitril/valsartan + placebo for weeks 1-12. and then sacubitril/valsartan only for weeks 13-32. All subjects in Group A will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device).	Group B Group B will receive an Angiotensin-Converting Enzyme Inhibitor (ACEi) or Angiotensin II Type 1 Receptor Blocker (ARB) + placebo for weeks 1-6 (depending on previous background therapy) and then switch to sacubitril/valsartan + placebo for weeks 7-12. Group B will then receive sacubitril/valsartan only for weeks 13-32. All subjects in Group B will also receive longitudinal pulmonary artery pressure monitoring using a previously placed implantable hemodynamic monitor (CardioMEMS device).
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Pulmonary Artery Pressure Reduction With ENTresto (Sacubitril/Valsartan)

Baseline characteristics by cohort

Measure	Group A n=2 Participants Entresto + Placebo	Group B n=2 Participants ACE/ARB + Placebo	Total n=4 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	57.5 years n=5 Participants	66.5 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
mean PA Pressure	24 mm Hg n=5 Participants	28 mm Hg n=7 Participants	26 mm Hg n=5 Participants
NTproBNP	634 pg/mL n=5 Participants	750 pg/mL n=7 Participants	692 pg/mL n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 6 weeks

Change in mean PAP in group A versus group B

Outcome measures

Measure	Group A n=2 Participants Entresto + Placebo	Group B n=2 Participants ACE/ARB + Placebo
Difference Between Mean Change in Mean Pulmonary Artery Pressure (PAPm) With Sacubitril/Valsartan Compared to the Mean Change in PAPm With Continued ACEi/ARB	0 mm Hg Interval 0.0 to 0.0	-2.5 mm Hg Interval -11.0 to 6.0

PRIMARY outcome

Timeframe: Baseline, 3 hours (after first dose of sacubitril/valsartan)

Change in PAPm at 3 hours

Outcome measures

Measure	Group A n=2 Participants Entresto + Placebo	Group B n=2 Participants ACE/ARB + Placebo
The Acute Change in PAPm After the First Administration of Sacubitril/Valsartan	-3.5 mm Hg Interval -8.0 to 1.0	-15 mm Hg Interval -15.0 to -15.0

SECONDARY outcome

Timeframe: 20 weeks (weeks 12 to 32 of the study)

Change in PAPm from week 12-32

Outcome measures

Measure	Group A n=1 Participants Entresto + Placebo	Group B n=2 Participants ACE/ARB + Placebo
Mean Change in PAPm in Both Groups on Sacubitril/Valsartan	6 mm Hg Interval 6.0 to 6.0	2 mm Hg Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: 6 weeks (week 1-6 of the study for group A, weeks 7-12 for group B)

Change in PAPm on sacubitril/valsartan: Measured from baseline to week 6 (group A) and week 7-week 12 (Group B)

Outcome measures

Measure	Group A n=2 Participants Entresto + Placebo	Group B n=2 Participants ACE/ARB + Placebo
The Difference Between Mean Change in PAPm From Baseline on Sacubitril/Valsartan Compared to ACEI/ARB	0 mm Hg Interval 0.0 to 0.0	1.5 mm Hg Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: Baseline, 6 weeks

Change in 6 minute walk distance in Group A vs. Group B at 6 weeks

Outcome measures

Measure	Group A n=2 Participants Entresto + Placebo	Group B n=2 Participants ACE/ARB + Placebo
Determine the Change in Distance Walked During a Standard 6 Minute Walk Test From Baseline	36 m Interval 8.0 to 63.0	-5 m Interval -30.0 to 20.0

SECONDARY outcome

Timeframe: Baseline

Change in NT-proBNP from baseline to 6 weeks

Outcome measures

Measure	Group A n=2 Participants Entresto + Placebo	Group B n=2 Participants ACE/ARB + Placebo
Change in NT-proBNP	-85 pg/mL Interval -136.0 to -33.0	250 pg/mL Interval -15.0 to 515.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 32 weeks (testing performed at intervals during study)

Population: Not reported due to lack of adequate data (too few participants enrolled)

Correlation between change in PAPm and change in KCCQ at 32 weeks

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 32 weeks (testing performed at intervals during study)

Population: \*\* Data not reported as too few participants were enrolled for meaningful analysis (n=4)

Mean change in total daily diuretic dose while on sacubitril/valsartan (32 weeks)

Outcome measures

Outcome data not reported

Adverse Events

Group A

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Group B

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Group A n=2 participants at risk Entresto + Placebo	Group B n=2 participants at risk ACE/ARB + Placebo
Cardiac disorders Heart Failure Hospitalization	50.0% 1/2 • Number of events 1 • 32 weeks No difference from standard definitions	0.00% 0/2 • 32 weeks No difference from standard definitions

Other adverse events

Adverse event data not reported

Additional Information

Akshay Desai

Brigham and Women's Hospital

Phone: 617-732-7046

Email: adesai@bwh.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place