serotonin transporter inhibitor escitalopram in pulmonary hypertension

Conditions: Pulmonary Hypertension

Summary: this is a phase iii, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of escitalopram (30 mg/day) in two parallel groups (randomization ratio, escitalopram 2/placebo 1).

primary objective: to evaluate the efficacy of oral escitalopram at the dosage of 30 mg/day for 16 weeks on the 6-minute walking test in patients with pulmonary hypertension.

Eligibility criteria:
inclusion criteria: subjects who meet all the criteria listed below will be considered for study inclusion: * male or female older than 18 years of age * meeting world health organization (who) criteria for pulmonary hypertension (mean pulmonary arterial pressure \[pap\] \> 25 mmhg at rest and pulmonary capillary wedge pressure \< 15 mmhg during right heart catheterization): * primary pulmonary hypertension (sporadic or familial), or * pulmonary hypertension associated with connective tissue diseases, or * pulmonary hypertension associated with hiv infection, or * pulmonary hypertension associated with use of appetite suppressants or other toxic compounds, or * pulmonary hypertension associated with shunting through a congenital heart defect surgically treated * class ii or iii in the nyha classification scheme * with a 6-minute walking test distance between 40% and 80% of theoretical values (approximately 50 and 480 m) * on conventional treatment, with no change in this treatment during the last month preceding the study. conventional treatment includes calcium antagonists or beraprost. * subject who consents to participate in the study. exclusion criteria: subjects with any of the following clinical features will not be included in the study: * pulmonary hypertension related to aortic or mitral valve disease, or extrinsic pulmonary vein compression * pulmonary hypertension related to hypoxia from respiratory disease with a total lung capacity \< 70% or tiffeneau index \< 60% upon testing within the last 6 months (chronic obstructive lung disease, interstitial disease, sleep apnea syndrome, alveolar hypoventilation, chronic exposure to high altitudes, neonatal lung disease, or alveolar capillary dysplasia) * pulmonary hypertension associated with portal hypertension * pulmonary hypertension secondary to chronic thrombosis and/or embolism (occlusion of the proximal or distal pulmonary arteries by thrombosis) * in the 6-minute walking test, inability to walk for 6 minutes, for any reason, or walking distance of less than 50 m * pregnancy, lactation, women of childbearing potential (if needed, effective contraception will be prescribed) * history of hypersensitivity to citalopram or to medications structurally related to citalopram * treatment with another investigational drug within the 3 months preceding study inclusion * cardiovascular, hepatic, neurological or endocrine disease that is clinically significant, or any other significant disease that may interfere with the study protocol or with the interpretation of study findings * history of drug or alcohol abuse * liver failure (except abnormalities related to the right ventricular failure) * kidney failure * mental status preventing the patient from understanding the nature, objectives, and possible consequences of the study * non stabilized psychiatric disorders * subject unable to comply with protocol-related constraints (e.g., uncooperative, unable to attend follow-up visits, and probably unable to complete the study).

Keywords: pulmonary hypertension 6 minutes walking test serotonin primary or associated pulmonary hypertension