Atorvastatin in Pulmonary Hypertension

NCT ID: NCT00615823

Last Updated: 2012-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2010-05-31

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.

Conditions

Hypertension, Pulmonary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Atorvastatin group: receive atorvastatin 10 mg daily in addition to supportive care

Group Type: ACTIVE_COMPARATOR

Atorvastatin

Intervention Type: DRUG

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.

2

Placebo group: receive matching placebo in addition to supportive care.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

atorvastatin: a'le(bland names); matching placebo: a'le(brand name)

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Grant from The Ministry of Science and Technology

UNKNOWN

Sponsor Role: collaborator

Capital Development Scientific Fund

UNKNOWN

Sponsor Role: collaborator

Chinese Academy of Medical Sciences, Fuwai Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jianguo He

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jianguo He, MD

Role: STUDY_CHAIR

Chinese Academy of Medical Sciences, Fuwai Hospital

Locations

Cardiovascular Institute and Fu Wai Hospital

Beijing, Beijing Municipality, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 22362846 (View on PubMed)

Other Identifiers

2006BAI01A07

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2005-1018

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2006-1152

Identifier Type: -

Identifier Source: org_study_id