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. Author manuscript; available in PMC: 2016 Jun 9.
Published in final edited form as: Circulation. 2015 Jun 9;131(23):2079–2091. doi: 10.1161/CIRCULATIONAHA.114.006980

Table 1.

Registered clinical trials investigating therapies that target neurohormonal activation in pulmonary arterial hypertension (PAH).

Study Name Identifier/Duration Treatment Inclusion Criteria Endpoint
fc
Primary Secondary
Beta-blockers for the treatment of PAH in children NCT01723371
6 mo
End date: 9/2014		 Carvedilol Age: ≥8 and ≤17.5 yr
mPAP >25 mmHg
PCWP <15 mmHg
PVR >3 Wood units
Clinically stable (3 mo)		 Adverse Event Incidence Δ 6MWD, VO2
Δ TAPSE
Δ RVEF
Beta-blockers in PAH NCT01246037
6 mo
End date: 4/2014		 Bisoprolol Age: ≥18 yr
Stable iPAH
WHO Class II/III		 ΔRVEF by CMR
Safety measures		 RV diastolic function
Sympathetic activity levels
PAH Treatment with Carvedilol for Heart Failure (PAHTCH) NCT01586156
6 months
End date: 7/2018		 Carvedilol Age: 18–65 yr
PAH
WHO Class I–III		 ΔHIF/NO/AR Recovery
ΔRV function
Pilot Study of the Safety and Efficacy of Carvedilol in PAH NCT00964678
6 mo
End date: 5/2014		 Carvedilol Age: ≥18 yr
WHO Group 1 PH
NHYA Class II/III
mPAP >25 mm Hg
6MWD >100m		 ΔRVEF by CMR ΔRVESV
Δ6MWD
ΔTAPSE
Spironolactone for PAH NCT01712620
6 mo
End date: 11/2015		 Spironolactone Age: ≥18 yr
WHO Group 1 PH
Stable therapy (4 wk)
mPAP >25 mmHg
PCWP<15 mmHg
PVR >3.0 Wood units
NYHA Class I–III		 Δ6MWD
Clinical worsening		 ΔVO2
ΔRV Function
Inflammation biomarkers
Drug Safety
Effects of Spironolactone on Collagen Metabolism in Patients with PAH NCT01468571
16 wk
End date: 12/2015		 Spironolactone Age: ≥18 yr
Body weight >40 kg
WHO Group 1 PH
Stable therapy (4 wk)		 Δ Fibrosis markers Adverse events
Δ6MWD
Δ Functional class
Clinical worsening
Modulating Effects of Lisinopril on Sildenafil Activity in PAH (MELISSA) NCT01181284
32 wk
End date: 7/2011		 Lisinopril added to sildenafil Age: 18–75 yr
WHO Group I PAH
PVR >3 Wood units
PCWP ≤16
6MWD 150–575 m
PDE-Vi (3 mo)		 ACE-I tolerability ΔN-BNP levels
Δ Gas exchange measures
Δ6MWD
Hormonal, Metabolic, and Signaling Interactions in PAH NCT01884051
5 yr
End date: 9/2017		 ACE-2 Metformin Sex hormone metabolite levels
Δ6MWD
Glucose metabolism		 Hemodynamics
PET scan results

NCT, national clinical trial (clinicaltrials.gov); mPAP, mean pulmonary artery pressure; PVR, pulmonary vascular resistance; PCWP, pulmonary capillary wedge pressure; 6MWD, 6-minute walk distance; VO2, peak volume of oxygen consumption; TAPSE, tricuspid annual plane excursion; RVEF, right ventricular ejection fraction; iPAH, idiopathic pulmonary arterial hypertension; WHO, World Health Organization; CMR, cardiac magnetic resonance; PH, pulmonary hypertension; NYHA, New York Heart Association; PDE-Vi, phosphodiesterase-type 5 inhibitor; ACE-I, angiotensin converting enzyme inhibitor; N-BNP, N-terminal brain natriuretic peptide; PET, positron emission tomography; mo, month; wk, week; yr, year.