PT  - JOURNAL ARTICLE
AU  - Aaron Waxman
AU  - Ronald Oudiz
AU  - Shelley Shapiro
AU  - Mardi Gomberg-Maitland
AU  - Anne Keogh
AU  - David Badesch
AU  - Robert Frantz
AU  - C. Gregory Elliott
AU  - Hunter Gillies
AU  - Gennyne Walker
TI  - Cicletanine in pulmonary arterial hypertension (PAH): Results from a phase 2 randomized placebo-controlled trial
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - 3274
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/3274.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/3274.full
SO  - Eur Respir J2012 Sep 01; 40
AB  - Cicletanine (CIC) is an antihypertensive with vasorelaxant and diuretic properties. Potential efficacy was observed with compassionate use of CIC in worsening PAH. A controlled study investigating the safety and efficacy of CIC for PAH was performed.162 subjects were randomized to 12 weeks of placebo (n=41) or CIC at doses of 150 mg qd (n=39), 150 mg bid (n=40) or 300 mg qd (n=42). Subjects could be on stable doses of an endothelin receptor antagonist, phosphodiesterase type 5 inhibitor, parenteral prostanoid, or any 2-drug combination. The primary analysis was comparison of change in 6-minute walk distance (6MWD) following 12 weeks of treatment with daily doses of CIC 300 mg (150 mg bid+300 mg qd; n=80) to placebo. Secondary analyses included dyspnea, WHO functional class, NT-proBNP, and a subset analysis of pulmonary hemodynamics (n=50).57.4% of subjects had idiopathic PAH and 42.6% associated PAH; 38.9% of subjects were WHO Class II, 61.1% WHO Class III and the mean baseline 6MWD was 370±64 meters (m). For the 300 mg combined group (n=80), the placebo-adjusted mean and median changes from baseline in 6MWD were +19.4 m (95% CI: 0.3, 38.4) and +7.0 m (95%: CI -8.0, 24.0), respectively (p=0.50). There were no clinically relevant improvements in the secondary assessments, including pulmonary vascular resistance (mean change 35 dyne·s/cm5). The adverse events reported more frequently with CIC were nausea, hypokalemia, and fatigue, consistent with known properties of diuretics.Although CIC was generally well-tolerated, no improvements in exercise tolerance, symptoms or hemodynamics were observed in patients with PAH after 12 weeks of CIC treatment.