Clinical trial NCT00964678: Pilot Study of the Safety and Efficacy of Carvedilol in Pulmonary Arterial Hypertension
Official title: Pilot Study of the Safety and Efficacy of Carvedilol in Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2009-08-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether carvedilol treatment of patients with pulmonary arterial hypertension and associated right heart failure is safe and results in an improved function of the right heart.

Detailed description: Patients with pulmonary arterial hypertension (PAH) will be treated with carvedilol for 24 weeks. During this time, carvedilol will be titrated from an initial dose of 3.125mg BID to a maximal dose of 25mg BID. At the start and end of the study, we will obtain cardiac MRI, 6 minute walk distance, brain natriuretic peptide (serum), echocardiogram, and functional class assessment. Our primary outcome is a change in right ventricular ejection fraction with cardiac MRI.

Eligibility criteria: Inclusion Criteria:

* idiopathic, familial or associated PAH, WHO group 1
* NYHA class II or III
* clinically stable with optimized PAH treatment for at least 3 months
* no or minimal evidence of fluid overload or volume depletion, with or without diuretic treatment
* age \> 18 years
* mean pulmonary artery pressure (mPAP) \> 25 mmHg
* 6 minute walk distance (6MWD) over 100m

Exclusion Criteria:

* Structural heart disease unrelated to PAH
* Recent (\<3 months) treatment with an intravenous positive inotropic agent
* current use of β-blockers
* history of reactive airways disease
* history of adverse reaction to β-blockers
* heart block on ECG or resting heart rate \< 60 bpm
* cardiac index \< 1.8 l/min/m2
* systemic hypotension (systolic pressure \< 90 mmHg)
* pulmonary capillary wedge pressure \> 15 mmHg
* inability to give informed consent
* contraindications to CT and/or PET scanning
* coagulopathy (INR\>1.5 or platelet count\<50000/mm3)
* severe renal insufficiency (creatinine clearance \<30 ml/min/m2)
* malignancy or any co-morbidity limiting survival or conditions predicting inability to complete the study.

Primary outcomes:
measure: Absolute Change in Right Ventricular Ejection Fraction
timeFrame: baseline, 6 months
Secondary outcomes:
measure: Change in Right Ventricular End Systolic Volume
timeFrame: baseline and 6 months
measure: Change in 6 Minute Walk Distance
timeFrame: baseline and 6 months
measure: Change in Tricuspid Annular Plane Systolic Excursion
timeFrame: baseline and 6 months
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Daniel C Grinnan, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grinnan D, Bogaard HJ, Grizzard J, Van Tassell B, Abbate A, DeWilde C, Priday A, Voelkel NF. Treatment of group I pulmonary arterial hypertension with carvedilol is safe. Am J Respir Crit Care Med. 2014 Jun 15;189(12):1562-4. doi: 10.1164/rccm.201311-2025LE. No abstract available.