Trial Outcomes & Findings for Mechanism(s) Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 1 (NCT NCT03738878)

NCT ID: NCT03738878

Last Updated: 2025-08-03

Results Overview

Forearm blood flow measured by strain gauge plethysmography before and after intra-arterial peptide infusion

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 4 participants
• Primary outcome timeframe: After four-week treatment with each crossover drug
• Results posted on: 2025-08-03

Participant Flow

Of four participants who were enrolled, one was randomized to treatment order and partially completed two study days. One participant met exclusion criteria. Two participants declined to participate after signing the consent form.

One participant met exclusion criteria. Two participants declined to participate after signing the consent form.

Participant milestones

Measure	Valsartan Then LCZ696 After four-week treatment with valsartan, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Then, after three-week washout and four-week therapy with LCZ696, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Valsartan: oral valsartan LCZ696: oral LCZ696 Bradykinin: Intra-arterial bradykinin at three graded doses Substance P: Intra-arterial substance P at three graded doses BNP: Intra-arterial BNP at three graded doses Sitagliptin: oral sitagliptin	LCZ696 Then Valsartan After four-week treatment with LCZ696, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Then, after three-week washout and four week therapy with valsartan, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Valsartan: oral valsartan LCZ696: oral LCZ696 Bradykinin: Intra-arterial bradykinin at three graded doses Substance P: Intra-arterial substance P at three graded doses BNP: Intra-arterial BNP at three graded doses Sitagliptin: oral sitagliptin
Overall Study STARTED	0	1
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Mechanism(s) Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 1

Baseline characteristics by cohort

Measure	Valsartan Then LCZ696 After four-week treatment with valsartan, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Then, after three-week washout and four week therapy with LCZ696, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Valsartan: oral valsartan LCZ696: oral LCZ696 Bradykinin: Intra-arterial bradykinin at three graded doses Substance P: Intra-arterial substance P at three graded doses BNP: Intra-arterial BNP at three graded doses Sitagliptin: oral sitagliptin	LCZ696 Then Valsartan n=1 Participants After four-week treatment with LCZ696, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Then, after three-week washout and four week therapy with valsartan, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Valsartan: oral valsartan LCZ696: oral LCZ696 Bradykinin: Intra-arterial bradykinin at three graded doses Substance P: Intra-arterial substance P at three graded doses BNP: Intra-arterial BNP at three graded doses Sitagliptin: oral sitagliptin	Total n=1 Participants Total of all reporting groups
Age, Continuous	—	45 years n=7 Participants	45 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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

PRIMARY outcome

Timeframe: After four-week treatment with each crossover drug

Population: Because the study was terminated data from only one participant are included and no statistical analyses were performed.

Forearm blood flow measured by strain gauge plethysmography before and after intra-arterial peptide infusion

Outcome measures

Measure	LCZ696 n=1 Participants Change in forearm blood flow before and after maximal dose of intraarterial bradykinin during LCZ696.	Valsartan n=1 Participants Change in forearm blood flow before and after maximal dose of intraarterial bradykinin during valsartan.
Forearm Blood Flow	2.46 mL/min/100mL Interval 2.46 to 2.46	2.99 mL/min/100mL Interval 2.99 to 2.99

Adverse Events

LCZ966

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Valsartan

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	LCZ966 n=1 participants at risk Adverse events that occurred on LCZ066 study day	Valsartan n=1 participants at risk Adverse events that occurred on valsartan study day.
Vascular disorders hypotension	100.0% 1/1 • Number of events 1 • Adverse event data were collected over the full duration of the study - approximately 12 weeks. The definition of adverse event and/or serious adverse event does not differ.	0.00% 0/1 • Adverse event data were collected over the full duration of the study - approximately 12 weeks. The definition of adverse event and/or serious adverse event does not differ.

Additional Information

Nancy J. Brown

Yale University

Phone: 2037854672

Email: nancy.j.brown@yale.edu

Results disclosure agreements

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