Trial Outcomes & Findings for PAHTCH Pulmonary Arterial Hypertension Treatment With Carvedilol for Heart Failure (Carvedilol) (NCT NCT01586156)
NCT ID: NCT01586156
Last Updated: 2018-12-05
Results Overview
We hypothesize that use of carvedilol in patients with PAH (Pulmonary Arterial Hypertension) will decrease the cardiac glucose utilization, and this will be measurable as a drop in fasting FDG-PET standardized uptake values of the heart at 6 months as compared to baseline
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
30 participants
Primary outcome timeframe
6 months
Results posted on
2018-12-05
Participant Flow
Participant milestones
| Measure |
Low-fixed-dose Carvedilol
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Placebo Arm
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Escalation-dose Carvedilol
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
9
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Low-fixed-dose Carvedilol
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Placebo Arm
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Escalation-dose Carvedilol
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
Overall Study
Pregnancy
|
0
|
1
|
0
|
Baseline Characteristics
PAHTCH Pulmonary Arterial Hypertension Treatment With Carvedilol for Heart Failure (Carvedilol)
Baseline characteristics by cohort
| Measure |
Low-fixed-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Escalation-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
Placebo Arm
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Total
n=30 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
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
42 years
STANDARD_DEVIATION 6 • n=5 Participants
|
53 years
STANDARD_DEVIATION 9 • n=7 Participants
|
38 years
STANDARD_DEVIATION 14 • n=5 Participants
|
42 years
STANDARD_DEVIATION 4 • n=4 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
30 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
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 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
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
23 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
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Paired analyses of baseline to 6 month FDG-PET SUV (standardized uptake value) within each group.
We hypothesize that use of carvedilol in patients with PAH (Pulmonary Arterial Hypertension) will decrease the cardiac glucose utilization, and this will be measurable as a drop in fasting FDG-PET standardized uptake values of the heart at 6 months as compared to baseline
Outcome measures
| Measure |
Placebo Arm
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Low-fixed-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Escalation-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
Cardiac Glucose Uptake in FDG-PET (Fluorodeoxyglucose-Positron Emission Tomography)
baseline FDG-PET
|
1.0 standardized uptake value (SUV)
Interval 0.6 to 1.4
|
0.6 standardized uptake value (SUV)
Interval 0.5 to 0.9
|
0.9 standardized uptake value (SUV)
Interval 0.5 to 1.5
|
|
Cardiac Glucose Uptake in FDG-PET (Fluorodeoxyglucose-Positron Emission Tomography)
6 month FDG-PET
|
0.8 standardized uptake value (SUV)
Interval 0.7 to 1.1
|
0.6 standardized uptake value (SUV)
Interval 0.4 to 0.8
|
0.7 standardized uptake value (SUV)
Interval 0.4 to 1.0
|
SECONDARY outcome
Timeframe: 6 monthsWe hypothesize that use of carvedilol in patients with PAH will increase beta adrenergic receptor function and this will be measurable as an increase in cAMP measured in the urine at 6 months in participants in dose escalation carvedilol.
Outcome measures
| Measure |
Placebo Arm
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Low-fixed-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Escalation-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
Urinary cAMP (Cyclic Adenosine Monophosphate)/Creatinine
baseline
|
1.4 umol/g
Interval 1.1 to 1.7
|
0.6 umol/g
Interval 0.4 to 0.9
|
1.0 umol/g
Interval 0.6 to 1.1
|
|
Urinary cAMP (Cyclic Adenosine Monophosphate)/Creatinine
1 month
|
1.3 umol/g
Interval 0.8 to 1.4
|
0.8 umol/g
Interval 0.5 to 1.1
|
0.7 umol/g
Interval 0.5 to 0.8
|
|
Urinary cAMP (Cyclic Adenosine Monophosphate)/Creatinine
3 months
|
1.2 umol/g
Interval 0.8 to 1.8
|
0.6 umol/g
Interval 0.5 to 1.0
|
1.5 umol/g
Interval 0.6 to 1.7
|
|
Urinary cAMP (Cyclic Adenosine Monophosphate)/Creatinine
6 months
|
1.4 umol/g
Interval 0.9 to 2.3
|
0.7 umol/g
Interval 0.4 to 1.5
|
1.0 umol/g
Interval 0.8 to 1.4
|
SECONDARY outcome
Timeframe: 6 monthsWe hypothesize that use of carvedilol in patients with PAH will increase beta- adrenergic receptor availability, and this will be measurable as a increase in alprenolol binding over time of drug use.
Outcome measures
| Measure |
Placebo Arm
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Low-fixed-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Escalation-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
Beta-Adrenergic Receptor (Alprenolol Binding Assay)
baseline
|
92254 abritrary units
Standard Deviation 21469
|
85230 abritrary units
Standard Deviation 18525
|
82779 abritrary units
Standard Deviation 30406
|
|
Beta-Adrenergic Receptor (Alprenolol Binding Assay)
6 months
|
79083 abritrary units
Standard Deviation 22337
|
84554 abritrary units
Standard Deviation 22828
|
83730 abritrary units
Standard Deviation 20455
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsWe hypothesized that RVSP might decrease in participants on carvedilol.
Outcome measures
| Measure |
Placebo Arm
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Low-fixed-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Escalation-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
Echocardiogram Right Ventricular Systolic Pressure (RVSP)
baseline
|
76 mm Hg
Standard Deviation 22
|
63 mm Hg
Standard Deviation 28
|
63 mm Hg
Standard Deviation 31
|
|
Echocardiogram Right Ventricular Systolic Pressure (RVSP)
3 months
|
78 mm Hg
Standard Deviation 21
|
59 mm Hg
Standard Deviation 18
|
54 mm Hg
Standard Deviation 24
|
|
Echocardiogram Right Ventricular Systolic Pressure (RVSP)
6 months
|
66 mm Hg
Standard Deviation 23
|
51 mm Hg
Standard Deviation 22
|
64 mm Hg
Standard Deviation 32
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsWe hypothesized that carvedilol would not worsen 6 minute walk distance.
Outcome measures
| Measure |
Placebo Arm
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Low-fixed-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Escalation-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
6 Minute Walk Test
baseline
|
404 meters
Standard Deviation 84
|
504 meters
Standard Deviation 93
|
438 meters
Standard Deviation 158
|
|
6 Minute Walk Test
3 months
|
412 meters
Standard Deviation 84
|
504 meters
Standard Deviation 93
|
438 meters
Standard Deviation 159
|
|
6 Minute Walk Test
6 months
|
453 meters
Standard Deviation 60
|
486 meters
Standard Deviation 90
|
450 meters
Standard Deviation 180
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsWe hypothesized that carvedilol would be safe and tolerable and thus that NT-BNP, a measure of heart failure, would not increase in participants on carvedilol.
Outcome measures
| Measure |
Placebo Arm
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Low-fixed-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Escalation-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
NT-proBNP (N-terminal Pro-B Type Natriuretic Peptide)
baseline
|
170 pg/ml
Interval 37.0 to 492.0
|
57 pg/ml
Interval 28.0 to 167.0
|
127 pg/ml
Interval 14.0 to 518.0
|
|
NT-proBNP (N-terminal Pro-B Type Natriuretic Peptide)
1 month
|
183 pg/ml
Interval 68.0 to 370.0
|
92 pg/ml
Interval 69.0 to 208.0
|
120 pg/ml
Interval 74.0 to 639.0
|
|
NT-proBNP (N-terminal Pro-B Type Natriuretic Peptide)
3 months
|
152 pg/ml
Interval 41.0 to 487.0
|
79 pg/ml
Interval 36.0 to 138.0
|
169 pg/ml
Interval 50.0 to 467.0
|
|
NT-proBNP (N-terminal Pro-B Type Natriuretic Peptide)
6 months
|
293 pg/ml
Interval 59.0 to 495.0
|
52 pg/ml
Interval 32.0 to 124.0
|
146 pg/ml
Interval 55.0 to 348.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsWe hypothesized that carvedilol would be safe and tolerable and thus that Left ventricular cardiac output, a measure of heart function, would not decrease in participants on carvedilol.
Outcome measures
| Measure |
Placebo Arm
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Low-fixed-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Escalation-dose Carvedilol
n=10 Participants
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
Echocardiogram Left Ventricular Cardiac Output
baseline
|
4.7 L/min
Standard Deviation 1.7
|
5.2 L/min
Standard Deviation 2
|
4.5 L/min
Standard Deviation 0.9
|
|
Echocardiogram Left Ventricular Cardiac Output
3 months
|
4.7 L/min
Standard Deviation 1.2
|
4.6 L/min
Standard Deviation 1.2
|
4.8 L/min
Standard Deviation 1.1
|
|
Echocardiogram Left Ventricular Cardiac Output
6 months
|
4.5 L/min
Standard Deviation 0.9
|
4.7 L/min
Standard Deviation 1.6
|
4.9 L/min
Standard Deviation 1.7
|
Adverse Events
Placebo Arm
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Low-fixed-dose Carvedilol
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Escalation-dose Carvedilol
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo Arm
n=10 participants at risk
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Low-fixed-dose Carvedilol
n=10 participants at risk
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Escalation-dose Carvedilol
n=10 participants at risk
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chest pain
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea/wheezing
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Cardiac disorders
Leg swelling
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Gastrointestinal disorders
Nausea/vomiting
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
Other adverse events
| Measure |
Placebo Arm
n=10 participants at risk
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study.
Carvedilol placebo: Placebo taken twice daily for 6 months
|
Low-fixed-dose Carvedilol
n=10 participants at risk
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months. This is the low fixed dose Carvedilol
|
Escalation-dose Carvedilol
n=10 participants at risk
Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. This is the escalating dose Carvedilol
|
|---|---|---|---|
|
Cardiac disorders
Leg swelling
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Nervous system disorders
Fatigue/vivid dreams
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Cardiac disorders
Cough/leg swelling
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Eye disorders
Blurry vision
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Gastrointestinal disorders
Cholecystitis
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Musculoskeletal and connective tissue disorders
Broken arm
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Nervous system disorders
Dizziness
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Respiratory, thoracic and mediastinal disorders
Site infection/acute bronchitis
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
|
Reproductive system and breast disorders
Bloating
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
0.00%
0/10 • Adverse event data was collected during the duration the subject was consented to participate in the study; 24 weeks or until discontinuation
the definition of adverse event and/or serious adverse event reporting does not differ from the definition listed
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place