Clinical trial NCT00615823: Atorvastatin in Pulmonary Hypertension
Official title: Clinical Effect and Tolerability of Atorvastatin Versus Placebo in Patients With Pulmonary Hypertension: Double-blinded, Randomised, Prospective Phase II Study for 6 Months With Adjusted Doses of Atorvastatin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension, Pulmonary
Keywords: Pulmonary Arterial Hypertension
Lead sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
Sponsor class: OTHER
Collaborators: name: National Grant from The Ministry of Science and Technology
name: Capital Development Scientific Fund
First posted: 2008-02-14
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Clinical effect and tolerability of atorvastatin versus placebo in patients with Pulmonary Hypertension: double-blinded, randomised, prospective phase II study for 6 months with adjusted doses of Atorvastatin

Detailed description: PAH is characterized by dyspnea, fatigue, and lower extremity edema as a result of heart failure. Several research have proved that inflammation may participate in the pathogenesis of PAH. As atorvastatin inhibits inflammation and has beneficial effects on blood vessels in other types of cardiovascular disease. Therefore, atorvastatin may similarly benefit patients with PAH. Experimental data suggest that statins attenuates pulmonary hypertension in animal experiments. In addition, non-controlled clinical studies suggest that atorvastatin is effective and safe in patients with pulmonary hypertension.

Participants in this study will be randomly assigned to receive 6 months of daily placebo tablets or daily atorvastatin in a double-blind fashion. The study will compare the safety and efficacy of placebo and atorvastatin.

Eligibility criteria: Inclusion Criteria:

* Able to understand and willing to sign the informed consent form
* \<=65 and \>=18years old
* Diagnosis of pulmonary arterial hypertension (Mean pulmonary artery pressure greater than 25 mm Hg at rest with a pulmonary capillary wedge pressure less than 15 mm Hg )that is a) idiopathic, b) familial, or c) associated with connective-tissue disease, d)congenital systemic-to-pulmonary shunt occurring after surgical/interventional repair that had been performed at least five years previously or in the absence of indications for surgery/intervention treatment e) chronic thromboembolism PAH in the absence of indications for surgery
* Patients in WHO functional class II to III
* Vasodilator Testing nonresponders
* Baseline six-minute walking distance between 100 and 460 m

Exclusion Criteria:

* PAH related to other etiologies (Groups 2, 3 and 5 pulmonary hypertension)
* A forced expiratory volume in one second/ forced vital capacity bellow 50% or a total lung capacity of less than 60 percent predicted value
* A 6-minute walk distance of less than 100 or more than 460 m
* A positive acute vasodilator response
* Current treatment with calcium-channel blockers or specific therapy (endothelin receptor antagonist, phosphodiesterase-5 inhibitor, or prostacyclin)
* Inability to perform 6-minute walk test
* Serum transaminase level three times above the upper limit of normal
* Creatine kinase level five times above the upper limit of normal
* Previously diagnosed heart disease such as serious cardiac arrhythmias, unstable angina pectoris, myocardial infarction
* History of transient ischemia attack or stroke within three months
* Bleeding disorder
* Positive pregnancy test or breastfeeding practice
* History or suspicion of inability to cooperate

Primary outcomes:
measure: The placebo-corrected change from baseline to week 24 in 6-minute walk distance
timeFrame: Measured at 6 months
Secondary outcomes:
measure: Time from randomization to clinical worsening
timeFrame: Measured at 6 months
measure: Change from baseline to week 24 in World Health Organization functional class
timeFrame: measured at 6 monthes
measure: Change from baseline to week 24 in Borg dyspnea score
timeFrame: measured at 6 monthes
measure: Change from baseline to week 24 in hemodynamic parameters derived from right heart catheterization.
timeFrame: measured at 6 monthes
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cardiovascular Institute and Fu Wai Hospital
state: Beijing
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Jianguo He, MD
role: STUDY_CHAIR
References:
citation: Zeng WJ, Xiong CM, Zhao L, Shan GL, Liu ZH, Xue F, Gu Q, Ni XH, Zhao ZH, Cheng XS, Wilkins MR, He JG; Atorvastatin in Pulmonary Arterial Hypertension (APATH) Study Group. Atorvastatin in pulmonary arterial hypertension (APATH) study. Eur Respir J. 2012 Jul;40(1):67-74. doi: 10.1183/09031936.00149011. Epub 2012 Feb 23.