Trial Outcomes & Findings for Nebivolol and Endothelial Regulation of Fibrinolysis (NERF) (NCT NCT01595516)
NCT ID: NCT01595516
Last Updated: 2019-06-25
Results Overview
Net endothelial release of t-PA antigen in response to bradykinin (BDK) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK). t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
44 participants
Primary outcome timeframe
t-PA release was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
Results posted on
2019-06-25
Participant Flow
Participant milestones
| Measure |
Nebivolol
Nebivolol: 5 mg tablet to be taken by mouth once per day for 12 weeks
|
Metoprolol
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Placebo
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
|---|---|---|---|
|
Overall Study
STARTED
|
16
|
16
|
12
|
|
Overall Study
COMPLETED
|
16
|
16
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nebivolol and Endothelial Regulation of Fibrinolysis (NERF)
Baseline characteristics by cohort
| Measure |
Nebivolol
n=16 Participants
Nebivolol: 5 mg tablet to be taken by mouth once per day for 12 weeks
|
Metoprolol
n=16 Participants
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Placebo
n=12 Participants
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
58 years
STANDARD_DEVIATION 5 • n=5 Participants
|
58 years
STANDARD_DEVIATION 6 • n=7 Participants
|
57 years
STANDARD_DEVIATION 6 • n=5 Participants
|
58 years
STANDARD_DEVIATION 6 • n=4 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
40 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 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
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
16 participants
n=7 Participants
|
12 participants
n=5 Participants
|
44 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Heart rate was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.Resting heart rate in the seated position
Outcome measures
| Measure |
Nebivolol
n=16 Participants
Nebivolol: 5 mg tablet to be taken by mouth once per day for 12 weeks
|
Metoprolol
n=16 Participants
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Placebo
n=12 Participants
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
After Metoprolol
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Before Placebo
Before randomization to placebo
|
After Placebo
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
|---|---|---|---|---|---|---|
|
Heart Rate
After Intervention
|
58 bpm
Standard Error 2
|
64 bpm
Standard Error 3
|
72 bpm
Standard Error 2
|
—
|
—
|
—
|
|
Heart Rate
Before Intervention
|
64 bpm
Standard Error 1
|
71 bpm
Standard Error 1
|
69 bpm
Standard Error 2
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Systolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.Outcome measures
| Measure |
Nebivolol
n=16 Participants
Nebivolol: 5 mg tablet to be taken by mouth once per day for 12 weeks
|
Metoprolol
n=16 Participants
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Placebo
n=12 Participants
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
After Metoprolol
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Before Placebo
Before randomization to placebo
|
After Placebo
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
|---|---|---|---|---|---|---|
|
Systolic Blood Pressure
Before Intervention
|
140 mmHg
Standard Error 2
|
138 mmHg
Standard Error 2
|
138 mmHg
Standard Error 2
|
—
|
—
|
—
|
|
Systolic Blood Pressure
After Intervention
|
125 mmHg
Standard Error 2
|
125 mmHg
Standard Error 3
|
135 mmHg
Standard Error 3
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Diastolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.Outcome measures
| Measure |
Nebivolol
n=16 Participants
Nebivolol: 5 mg tablet to be taken by mouth once per day for 12 weeks
|
Metoprolol
n=16 Participants
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Placebo
n=12 Participants
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
After Metoprolol
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Before Placebo
Before randomization to placebo
|
After Placebo
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
|---|---|---|---|---|---|---|
|
Diastolic Blood Pressure
Before Intervention
|
85 mmHg
Standard Error 2
|
87 mmHg
Standard Error 2
|
85 mmHg
Standard Error 3
|
—
|
—
|
—
|
|
Diastolic Blood Pressure
After Intervention
|
78 mmHg
Standard Error 2
|
79 mmHg
Standard Error 2
|
81 mmHg
Standard Error 2
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: t-PA release was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.Net endothelial release of t-PA antigen in response to bradykinin (BDK) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK). t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells.
Outcome measures
| Measure |
Nebivolol
n=16 Participants
Nebivolol: 5 mg tablet to be taken by mouth once per day for 12 weeks
|
Metoprolol
n=16 Participants
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Placebo
n=16 Participants
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
After Metoprolol
n=16 Participants
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Before Placebo
n=12 Participants
Before randomization to placebo
|
After Placebo
n=12 Participants
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
|---|---|---|---|---|---|---|
|
Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention
Amount of t-PA release to Saline
|
-1.2 ng/100 mL tissue/min
Standard Error 0.8
|
-1.8 ng/100 mL tissue/min
Standard Error 0.9
|
-1.2 ng/100 mL tissue/min
Standard Error 1.2
|
-1.9 ng/100 mL tissue/min
Standard Error 1.1
|
-0.2 ng/100 mL tissue/min
Standard Error 1.2
|
-0.9 ng/100 mL tissue/min
Standard Error 1.5
|
|
Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention
Amount of t-PA release to BDK 12.5
|
15.7 ng/100 mL tissue/min
Standard Error 2.9
|
25.2 ng/100 mL tissue/min
Standard Error 4.1
|
14.4 ng/100 mL tissue/min
Standard Error 3.3
|
16.6 ng/100 mL tissue/min
Standard Error 3.3
|
18.1 ng/100 mL tissue/min
Standard Error 3.1
|
17.6 ng/100 mL tissue/min
Standard Error 2.8
|
|
Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention
Amount of t-PA release to BDK 25.0
|
29.1 ng/100 mL tissue/min
Standard Error 3.9
|
46.4 ng/100 mL tissue/min
Standard Error 6.5
|
27.5 ng/100 mL tissue/min
Standard Error 3.3
|
31.2 ng/100 mL tissue/min
Standard Error 2.4
|
28.3 ng/100 mL tissue/min
Standard Error 3.8
|
32.7 ng/100 mL tissue/min
Standard Error 5.6
|
|
Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention
Amount of t-PA release to BDK 50.0
|
47.2 ng/100 mL tissue/min
Standard Error 4.3
|
72.8 ng/100 mL tissue/min
Standard Error 5.7
|
48.2 ng/100 mL tissue/min
Standard Error 5.9
|
52.7 ng/100 mL tissue/min
Standard Error 4.6
|
51.1 ng/100 mL tissue/min
Standard Error 5.0
|
52.9 ng/100 mL tissue/min
Standard Error 4.3
|
PRIMARY outcome
Timeframe: t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.Net endothelial release of t-PA antigen in response to bradykinin (BDK) and bradykinin+vitamin C (BDK+C) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK) and BDK+Vit C. t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells.
Outcome measures
| Measure |
Nebivolol
n=10 Participants
Nebivolol: 5 mg tablet to be taken by mouth once per day for 12 weeks
|
Metoprolol
n=10 Participants
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Placebo
n=10 Participants
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
After Metoprolol
n=10 Participants
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Before Placebo
Before randomization to placebo
|
After Placebo
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
|---|---|---|---|---|---|---|
|
Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy.
Amount of t-PA release to BDK 12.5
|
14.3 ng/100 mL tissue/min
Standard Error 3.2
|
31.3 ng/100 mL tissue/min
Standard Error 5.5
|
28.2 ng/100 mL tissue/min
Standard Error 6.2
|
38.1 ng/100 mL tissue/min
Standard Error 7.3
|
—
|
—
|
|
Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy.
Amount of t-PA release to saline
|
-2.4 ng/100 mL tissue/min
Standard Error 1.1
|
-1.4 ng/100 mL tissue/min
Standard Error 0.8
|
-1.5 ng/100 mL tissue/min
Standard Error 1.3
|
-3.8 ng/100 mL tissue/min
Standard Error 2.6
|
—
|
—
|
|
Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy.
Amount of t-PA release to BDK 25.0
|
27.6 ng/100 mL tissue/min
Standard Error 5.0
|
52.7 ng/100 mL tissue/min
Standard Error 6.6
|
49.1 ng/100 mL tissue/min
Standard Error 9.1
|
54.2 ng/100 mL tissue/min
Standard Error 7.9
|
—
|
—
|
|
Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy.
Amount of t-PA release to BDK 50.0
|
47.2 ng/100 mL tissue/min
Standard Error 5.0
|
80.5 ng/100 mL tissue/min
Standard Error 6.2
|
67.5 ng/100 mL tissue/min
Standard Error 7.1
|
79.9 ng/100 mL tissue/min
Standard Error 7.6
|
—
|
—
|
PRIMARY outcome
Timeframe: t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.Net endothelial release of t-PA antigen in response to BDK and BDK+C was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK) and BDK+Vit C. t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells.
Outcome measures
| Measure |
Nebivolol
n=10 Participants
Nebivolol: 5 mg tablet to be taken by mouth once per day for 12 weeks
|
Metoprolol
n=10 Participants
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Placebo
n=10 Participants
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
After Metoprolol
n=10 Participants
Metoprolol: 100 mg tablet to be taken by mouth once per day for 12 weeks
|
Before Placebo
Before randomization to placebo
|
After Placebo
Placebo: Gelatin capsule to be taken by mouth once per day for 12 weeks
|
|---|---|---|---|---|---|---|
|
Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy.
Amount of t-PA release to BDK 12.5
|
10.1 ng/100 mL tissue/min
Standard Error 3.9
|
31.1 ng/100 mL tissue/min
Standard Error 5.0
|
16.4 ng/100 mL tissue/min
Standard Error 5.0
|
30.0 ng/100 mL tissue/min
Standard Error 4.4
|
—
|
—
|
|
Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy.
Amount of t-PA release to Saline
|
-2.7 ng/100 mL tissue/min
Standard Error 0.9
|
-2.5 ng/100 mL tissue/min
Standard Error 0.8
|
-1.3 ng/100 mL tissue/min
Standard Error 1.4
|
-2.7 ng/100 mL tissue/min
Standard Error 1.1
|
—
|
—
|
|
Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy.
Amount of t-PA release to BDK 25.0
|
24.5 ng/100 mL tissue/min
Standard Error 3.8
|
47.1 ng/100 mL tissue/min
Standard Error 7.3
|
31.3 ng/100 mL tissue/min
Standard Error 3.3
|
46.4 ng/100 mL tissue/min
Standard Error 6.3
|
—
|
—
|
|
Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy.
Amount of t-PA release to BDK 50.0
|
45.0 ng/100 mL tissue/min
Standard Error 5.5
|
82.4 ng/100 mL tissue/min
Standard Error 10.2
|
49.9 ng/100 mL tissue/min
Standard Error 5.7
|
73.8 ng/100 mL tissue/min
Standard Error 7.4
|
—
|
—
|
Adverse Events
Nebivolol
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Metoprolol
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place