Trial Outcomes & Findings for Vericiguat in Patients With Metabolic Syndrome and Coronary Vascular Dysfunction (NCT NCT05711719)

NCT ID: NCT05711719

Last Updated: 2026-01-27

Results Overview

The difference in absolute change in coronary cross-sectional area (in mm²) from rest to isometric handgrip exercise (IHE) in the group randomized to vericiguat from that measured at baseline, prior to the initiation of vericiguat, to that measured at the end of the study drug administration period, six weeks following initiation of the titrated dose, as assessed by MRI.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

Baseline and 6 weeks following initiation of up-titrated dose

Results posted on

2026-01-27

Participant Flow

A total of 45 participants were enrolled (provided written informed consent) and underwent screening MRI. 11 participants were excluded from the study before assignment to veiciguat or placebo: six had normal coronary endothelial function, image quality was poor in two, one experienced claustrophobia, one withdrew and one was lost to follow-up. 34 participants were subsequently randomized.

Participant milestones

Participant milestones
Measure
Vericiguat
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily. Vericiguat: Up-titration will be performed as guided by the evaluation of blood pressure and clinical symptoms
Placebo
A placebo tablet will be administered orally once daily. Placebo: Administered the same way
Overall Study
STARTED
23
11
Overall Study
COMPLETED
21
11
Overall Study
NOT COMPLETED
2
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vericiguat in Patients With Metabolic Syndrome and Coronary Vascular Dysfunction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Vericiguat
n=23 Participants
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily. Vericiguat: Up-titration will be performed as guided by the evaluation of blood pressure and clinical symptoms
Placebo
n=11 Participants
A placebo tablet will be administered orally once daily. Placebo: Administered the same way
Total
n=34 Participants
Total of all reporting groups
Age, Continuous
61.1 years
STANDARD_DEVIATION 8.9 • n=41 Participants
59.6 years
STANDARD_DEVIATION 7.5 • n=1581 Participants
60.6 years
STANDARD_DEVIATION 8.6 • n=4626 Participants
Sex: Female, Male
Female
7 Participants
n=41 Participants
7 Participants
n=1581 Participants
14 Participants
n=4626 Participants
Sex: Female, Male
Male
16 Participants
n=41 Participants
4 Participants
n=1581 Participants
20 Participants
n=4626 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=41 Participants
0 Participants
n=1581 Participants
0 Participants
n=4626 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
23 Participants
n=41 Participants
11 Participants
n=1581 Participants
34 Participants
n=4626 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=41 Participants
0 Participants
n=1581 Participants
0 Participants
n=4626 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=41 Participants
0 Participants
n=1581 Participants
0 Participants
n=4626 Participants
Race (NIH/OMB)
Asian
3 Participants
n=41 Participants
0 Participants
n=1581 Participants
3 Participants
n=4626 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=41 Participants
0 Participants
n=1581 Participants
0 Participants
n=4626 Participants
Race (NIH/OMB)
Black or African American
2 Participants
n=41 Participants
2 Participants
n=1581 Participants
4 Participants
n=4626 Participants
Race (NIH/OMB)
White
18 Participants
n=41 Participants
9 Participants
n=1581 Participants
27 Participants
n=4626 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=41 Participants
0 Participants
n=1581 Participants
0 Participants
n=4626 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=41 Participants
0 Participants
n=1581 Participants
0 Participants
n=4626 Participants

PRIMARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

Population: Two participants who were assigned to the Vericiguat group withdrew. One withdrew due to personal bereavement following the unexpected death of a close friend, and the other withdrew due to lightheadedness and nausea following alcohol intake.

The difference in absolute change in coronary cross-sectional area (in mm²) from rest to isometric handgrip exercise (IHE) in the group randomized to vericiguat from that measured at baseline, prior to the initiation of vericiguat, to that measured at the end of the study drug administration period, six weeks following initiation of the titrated dose, as assessed by MRI.

Outcome measures

Outcome measures
Measure
Vericiguat (Baseline)
n=21 Participants
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily. Vericiguat: Up-titration will be performed as guided by the evaluation of blood pressure and clinical symptoms
Vericiguat Group (Follow-up Visit)
n=21 Participants
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily.
Absolute Change in Coronary Cross-sectional Area (in mm²) Within the Vericiguat Group as Assessed by Magnetic Resonance Imaging (MRI)
-1.11 mm^2
Standard Deviation 1.17
0.40 mm^2
Standard Deviation 1.28

PRIMARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

Population: Two participants who were assigned to the vericiguat group withdrew. One withdrew due to personal bereavement following the unexpected death of a close friend, and the other withdrew due to lightheadedness and nausea following alcohol intake.

The difference in relative change in coronary cross-sectional area (in %) from rest to isometric handgrip exercise (IHE) in the group randomized to vericiguat from that measured at baseline prior to the initiation of vericiguat, to that measured at the end of the study drug administration period, six weeks following initiation of the titrated dose, as assessed by MRI.

Outcome measures

Outcome measures
Measure
Vericiguat (Baseline)
n=21 Participants
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily. Vericiguat: Up-titration will be performed as guided by the evaluation of blood pressure and clinical symptoms
Vericiguat Group (Follow-up Visit)
n=21 Participants
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily.
Relative Change in Coronary Cross-sectional Area (as Percentage) Within the Vericiguat Group as Assessed by Magnetic Resonance Imaging (MRI)
-6.8 percent change
Standard Deviation 6.7
3.1 percent change
Standard Deviation 8.5

PRIMARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

Population: In the vericiguat arm, two participants withdrew. One withdrew due to personal bereavement following the unexpected death of a close friend, and the other withdrew due to lightheadedness and nausea following alcohol intake.

The difference in absolute change in coronary cross-sectional area (in mm²) from rest to isometric handgrip exercise (IHE) as assessed by MRI.

Outcome measures

Outcome measures
Measure
Vericiguat (Baseline)
n=21 Participants
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily. Vericiguat: Up-titration will be performed as guided by the evaluation of blood pressure and clinical symptoms
Vericiguat Group (Follow-up Visit)
n=11 Participants
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily.
Absolute Change in Coronary Cross-sectional Area (in mm²) Between the Vericiguat Group and the Placebo Group as Assessed by Magnetic Resonance Imaging (MRI)
0.40 mm^2
Standard Deviation 1.28
-0.003 mm^2
Standard Deviation 1.18

PRIMARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

Population: In the vericiguat arm, two participants withdrew. One withdrew due to personal bereavement following the unexpected death of a close friend, and the other withdrew due to lightheadedness and nausea following alcohol intake.

The difference in percentage change in coronary cross-sectional area (%) from rest to isometric handgrip exercise (IHE) between the vericiguat and placebo groups, as assessed from the baseline MRI to the follow-up MRI, six weeks following initiation of the titrated dose.

Outcome measures

Outcome measures
Measure
Vericiguat (Baseline)
n=21 Participants
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily. Vericiguat: Up-titration will be performed as guided by the evaluation of blood pressure and clinical symptoms
Vericiguat Group (Follow-up Visit)
n=11 Participants
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily.
Difference in Percent Change in Coronary Cross-sectional Area (as Percentage) Between the Vericiguat Group and the Placebo Group as Assessed by Magnetic Resonance Imaging (MRI)
9.9 % change coronary cross-sectional area
Standard Deviation 9.80
8.8 % change coronary cross-sectional area
Standard Deviation 13.20

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

IL-1 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

IL-6 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

IL-10 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

TNF-alpha (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

hsCRP (in mg/L), an inflammatory marker, will be measured in blood samples to assess changes from baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

cGMP (in pmol/mL), a mediator in the nitric oxide pathway, will be measured in blood samples to assess changes from baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

An ultrasound evaluation of the heart will be performed to assess the impact of vericiguat on left ventricular ejection fraction (%).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

An ultrasound evaluation of the heart will be performed to assess the impact of vericiguat on e' velocities (in cm/s).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

An ultrasound evaluation of the heart will be performed to assess the impact of vericiguat on the E/e' ratio.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

An ultrasound evaluation of the heart will be performed to assess the impact of vericiguat on the left atrium volume index (in mL/BSA).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

An ultrasound evaluation of the heart will be performed to assess the impact of vericiguat on peak TR velocity (in m/s).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

An ultrasound evaluation of the heart will be performed to assess the impact of vericiguat on strain (as percentage).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

The absolute changes in coronary flow (in mL/min) with isometric handgrip exercise (IHE) in the group randomized to vericiguat from that measured at baseline, prior to the initiation of vericiguat, to that measured at the end of the study drug administration period as assessed by MRI.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

The relative changes in coronary flow (as percentage) with isometric handgrip exercise (IHE) in the group randomized to vericiguat from that measured at baseline, prior to the initiation of vericiguat, to that measured at the end of the study drug administration period as assessed by MRI.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

The absolute changes in coronary flow (in mL/min) with isometric handgrip exercise (IHE) in the vericiguat group as compared to the placebo group as assessed by MRI.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 weeks following initiation of up-titrated dose

The relative changes in in coronary flow (as percentage) with isometric handgrip exercise (IHE) in the vericiguat group as compared to the placebo group as assessed by MRI.

Outcome measures

Outcome data not reported

Adverse Events

Vericiguat

Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Vericiguat
n=23 participants at risk
Initial 2.5 mg/day for two weeks, then 5 mg/day for two weeks, and then 10 mg/day for two weeks. Systolic blood pressure will be measured before and following each titration The participant will receive the final titration dose for a total of six weeks.. The drug is administered as an oral tablet once daily. Vericiguat: Up-titration will be performed as guided by the evaluation of blood pressure and clinical symptoms
Placebo
n=11 participants at risk
A placebo tablet will be administered orally once daily. Placebo: Administered the same way
Vascular disorders
Orthostatic dizziness
8.7%
2/23 • up to 156 days
0.00%
0/11 • up to 156 days
Gastrointestinal disorders
Dysphagia
8.7%
2/23 • up to 156 days
0.00%
0/11 • up to 156 days
Gastrointestinal disorders
Heartburn
13.0%
3/23 • up to 156 days
0.00%
0/11 • up to 156 days
General disorders
Dizziness
4.3%
1/23 • up to 156 days
27.3%
3/11 • up to 156 days
General disorders
Unsteadiness
0.00%
0/23 • up to 156 days
18.2%
2/11 • up to 156 days
Nervous system disorders
Forgetfulness
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days
Gastrointestinal disorders
Nausea
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days
Gastrointestinal disorders
Vomiting after alcohol consumption
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days
General disorders
Fatigue
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days
Vascular disorders
Syncope
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days
Cardiac disorders
Palpitations after influenza vaccination
0.00%
0/23 • up to 156 days
9.1%
1/11 • up to 156 days
Social circumstances
Anxiety following mother's cancer diagnosis
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days
Cardiac disorders
Chest discomfort with exercise
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days
General disorders
Epitaxis
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days
Respiratory, thoracic and mediastinal disorders
Dry cough
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days
General disorders
Increased thirst
0.00%
0/23 • up to 156 days
9.1%
1/11 • up to 156 days
Skin and subcutaneous tissue disorders
Rash following yard work
0.00%
0/23 • up to 156 days
9.1%
1/11 • up to 156 days
Blood and lymphatic system disorders
Low hemoglobin
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days
General disorders
Low fasting glucose
4.3%
1/23 • up to 156 days
9.1%
1/11 • up to 156 days
General disorders
Low potassium
4.3%
1/23 • up to 156 days
0.00%
0/11 • up to 156 days

Additional Information

Thorsten M. Leucker, MD, PhD

Johns Hopkins University

Phone: (410) 502-9453

Results disclosure agreements

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