Pulmonary Arterial Hypertension
Conditions
Brief summary
The investigators will conduct a, randomized, phase 2, placebo-controlled, double-blinded, crossover trial of carvedilol in 26 PAH patients with World Health Organization functional class II or III symptoms and RV ejection fraction (EF) \< 45% for 6 months.
Detailed description
Adult PAH patients on a stable dose of an approved PAH medication will undergo the following baseline assessments: cardiac magnetic resonance imaging (MRI), right heart catheterization (RHC), echocardiogram, 6-minute walk test (6-MWT), plasma NT-ProBNP (biomarkers of RV function) and serum catecholamine (measure of sympathetic activation), and quality of life. Patients will be randomized to carvedilol (3.125 mg bid and escalated to 9.375 mg bid, as tolerated, over 3 months) or placebo in a 1:1 fashion. After 6 months, testing is repeated and patients are crossed over to the alternate treatment. Testing is repeated at the end of the study (month 13).
Interventions
DRUGCarvedilol
Beta-adrenergic receptor blocker
DRUGPlacebo
Placebo
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * WHO category 1 pulmonary arterial hypertension (Nice 2013) * WHO functional class II-III * RVEF by cardiac MRI \< 45% * Stable on PAH-specific therapy as defined by no change in PAH-specific treatment and functional class in the past 3 months. Patient can be on either mono or combination PAH-specific therapy
Exclusion criteria
* Subjects will be excluded from participation in the study if any of the following conditions exist: * Significant persistent bradycardia (resting heart rate \< 60 bpm) without a permanent pacemaker * Second or third degree AV block without a permanent pacemaker * Significant sinus tachycardia (resting heart rate \> 110 bpm) * Use of anti-arrhythmic drugs * Hypotension defined as systolic blood pressure \< 100 mmHg at the time of enrollment * Significant illness in the past 30 days requiring hospitalization * Acute decompensated right heart failure within past 30 days * Known allergy or intolerance to carvedilol or other β blockers * Cardiac index \< 2 l/min/m2 or right atrial pressure \> 15 mm Hg by right heart catheterization within last 3 months * Asthma * Positive pregnancy test in patients of child bearing-potential
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Change in Right Ventricular Ejection Fraction as Measured by Cardiac MRI | 6 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Crossover Design: All participants pooled at baseline | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 61.5 years STANDARD_DEVIATION 10.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 1 / 2 | 2 / 2 |
| serious Total, serious adverse events | 1 / 2 | 1 / 2 |
Outcome results
Primary
Mean Change in Right Ventricular Ejection Fraction as Measured by Cardiac MRI
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol | Mean Change in Right Ventricular Ejection Fraction as Measured by Cardiac MRI | 10 percent | Standard Deviation 4 |
| Placebo | Mean Change in Right Ventricular Ejection Fraction as Measured by Cardiac MRI | 2.5 percent | Standard Deviation 2 |