Trial Outcomes & Findings for Pilot Study of the Safety and Efficacy of Carvedilol in Pulmonary Arterial Hypertension (NCT NCT00964678)

Results Overview

Change in right ventricular ejection fraction is measured by cardiac magnetic resonance imaging, using the method of disks with the reading radiologist being blinded to before and after images. Cardiac magnetic resonance imaging was done at baseline and 6 months only

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

baseline, 6 months

Results posted on

2017-06-08

Participant Flow

Participant milestones

Participant milestones
Measure	Carvedilol Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI
Overall Study STARTED	10
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Carvedilol Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI
Overall Study Physician Decision	4

Baseline Characteristics

Pilot Study of the Safety and Efficacy of Carvedilol in Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carvedilol n=6 Participants Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI Carvedilol: twice daily oral treatment in escalating dose
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Age, Continuous	60.6 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants
Right ventricular ejection fraction of blood	38 % of ejected ventricular vol of blood n=5 Participants
Six minute walk distance	321 meters n=5 Participants

PRIMARY outcome

Timeframe: baseline, 6 months

Population: Patients with right heart catheterization confirmed pulmonary arterial hypertension, already on pulmonary vasodilator therapy

Change in right ventricular ejection fraction is measured by cardiac magnetic resonance imaging, using the method of disks with the reading radiologist being blinded to before and after images. Cardiac magnetic resonance imaging was done at baseline and 6 months only

Outcome measures

Outcome measures
Measure	Carvedilol n=6 Participants Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI Carvedilol: twice daily oral treatment in escalating dose
Absolute Change in Right Ventricular Ejection Fraction	10.4 % RVEF Interval 3.6 to 16.0

SECONDARY outcome

Timeframe: baseline and 6 months

right ventricular end systolic volume determined by MRI

Outcome measures

Outcome measures
Measure	Carvedilol n=6 Participants Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI Carvedilol: twice daily oral treatment in escalating dose
Change in Right Ventricular End Systolic Volume Participant 1	3 mL
Change in Right Ventricular End Systolic Volume Participant 2	14 mL
Change in Right Ventricular End Systolic Volume Participant 3	56 mL
Change in Right Ventricular End Systolic Volume Participant 4	11 mL
Change in Right Ventricular End Systolic Volume Participant 5	27 mL
Change in Right Ventricular End Systolic Volume Participant 6	25 mL

SECONDARY outcome

Timeframe: baseline and 6 months

Population: The patient who was excluded from analysis developed an orthopedic injury during the study and was unable to complete the walking test at conclusion of the study

Outcome measures

Outcome measures
Measure	Carvedilol n=5 Participants Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI Carvedilol: twice daily oral treatment in escalating dose
Change in 6 Minute Walk Distance Participant 3	35 feet
Change in 6 Minute Walk Distance Participant 5	5 feet
Change in 6 Minute Walk Distance Participant 1	45 feet
Change in 6 Minute Walk Distance Participant 2	160 feet
Change in 6 Minute Walk Distance Participant 6	96 feet

SECONDARY outcome

Timeframe: baseline and 6 months

Population: The patient excluded from the analysis was unable to be present for the final echo-cardiogram due to lack of transportation and distance from the hospital. Multiple attempts to schedule the study test were made through phone and email.

Higher values indicate a better outcome.

Outcome measures

Outcome measures
Measure	Carvedilol n=5 Participants Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI Carvedilol: twice daily oral treatment in escalating dose
Change in Tricuspid Annular Plane Systolic Excursion Participant 1	0.4 centimeters
Change in Tricuspid Annular Plane Systolic Excursion Participant 2	-0.08 centimeters
Change in Tricuspid Annular Plane Systolic Excursion Participant 4	-0.12 centimeters
Change in Tricuspid Annular Plane Systolic Excursion Participant 5	0.45 centimeters
Change in Tricuspid Annular Plane Systolic Excursion Participant 6	0.08 centimeters

Adverse Events

Carvedilol

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Carvedilol n=6 participants at risk Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI Carvedilol: twice daily oral treatment in escalating dose
Metabolism and nutrition disorders fatigue	16.7% 1/6 • Number of events 1 • 6 months
Cardiac disorders hypotension	16.7% 1/6 • Number of events 1 • 6 months

Additional Information

Dan Grinnan, MD

Virginia Commonwealth University Health System

Phone: 804-828-9000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place