Atorvastatin in Pulmonary Hypertension (APATH)

• ClinicalTrials.gov Identifier: NCT00615823
• Recruitment Status: Completed
• First Posted: February 14, 2008
• Last Update Posted: February 23, 2012
• Sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
• Collaborators: National Grant from The Ministry of Science and Technology; Capital Development Scientific Fund
• Information provided by (Responsible Party): Jianguo He, Chinese Academy of Medical Sciences, Fuwai Hospital

Study Description

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

Condition or disease	Intervention/treatment	Phase
Hypertension, Pulmonary	Drug: Atorvastatin; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: February 2007
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: May 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1; Atorvastatin group: receive atorvastatin 10 mg daily in addition to supportive care	Drug: Atorvastatin; Patients were assigned to receive 10 mg of atorvastatin for 6 months (supplied by JiaLin Pharmaceutical Co., Beijing, China). The dose was adjusted to 5mg daily if serum transaminase levels increased by less than three times the upper limit of normal or creatine kinase levels increased to less than five times the upper limit of normal. If serum transaminase and creatine kinase levels remained normal and low-density lipoprotein level greater than 3.4mmol/L after 4 weeks of therapy, the dose of drug was increased to 20mg once daily.; Other Name: atorvastatin: a'le(bland names)
Placebo Comparator: 2; Placebo group: receive matching placebo in addition to supportive care.	Drug: Placebo; Patients were assigned to receive 10 mg of placebo for 6 months (supplied by JiaLin Pharmaceutical Co., Beijing, China). The dose was adjusted to 5mg daily if serum transaminase levels increased by less than three times the upper limit of normal or creatine kinase levels increased to less than five times the upper limit of normal. If serum transaminase and creatine kinase levels remained normal and low-density lipoprotein level greater than 3.4mmol/L after 4 weeks of therapy, the dose of drug was increased to 20mg once daily.; Other Name: matching placebo: a'le(brand name)

Outcome Measures

Primary Outcome Measures :

1. The placebo-corrected change from baseline to week 24 in 6-minute walk distance [ Time Frame: Measured at 6 months ]

Secondary Outcome Measures :

1. Time from randomization to clinical worsening [ Time Frame: Measured at 6 months ]
   Clinical worsening was defined as death, the first occurrence of hospitalization for pulmonary arterial hypertension, or initiation of PAH-specific drug therapy
2. Change from baseline to week 24 in World Health Organization functional class [ Time Frame: measured at 6 monthes ]
   World Health Organization (WHO) functional class: an adaptation of the New York Heart Association classification.
3. Change from baseline to week 24 in Borg dyspnea score [ Time Frame: measured at 6 monthes ]
   Borg dyspnea score: with 0 representing no dyspnea and 10 maximal dyspnea.
4. Change from baseline to week 24 in hemodynamic parameters derived from right heart catheterization. [ Time Frame: measured at 6 monthes ]
   Hemodynamic parameters: mean pulmonary artery pressure, right atrial pressure, cardiac index and pulmonary vascular resistance.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

China, Beijing

Cardiovascular Institute and Fu Wai Hospital

Beijing, Beijing, China, 100037

Sponsors and Collaborators

Chinese Academy of Medical Sciences, Fuwai Hospital

National Grant from The Ministry of Science and Technology

Capital Development Scientific Fund

Investigators

• Study Chair: Jianguo He, MD; Chinese Academy of Medical Sciences, Fuwai Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Jianguo He, Professor, Chinese Academy of Medical Sciences, Fuwai Hospital
• ClinicalTrials.gov Identifier: NCT00615823
• Other Study ID Numbers: 2006-1152; 2006BAI01A07 ( Other Grant/Funding Number: National Grant from The Ministry of Science ); 2005-1018 ( Other Grant/Funding Number: Capital Development Scientific Fund )
• First Posted: February 14, 2008
• Last Update Posted: February 23, 2012
• Last Verified: February 2012

Keywords provided by Jianguo He, Chinese Academy of Medical Sciences, Fuwai Hospital:

Pulmonary Arterial Hypertension

Additional relevant MeSH terms:

Hypertension, Pulmonary; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Atorvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors