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Atorvastatin in Pulmonary Hypertension (APATH)

This study has been completed.
Sponsor:
Collaborators:
National Grant from The Ministry of Science and Technology
Capital Development Scientific Fund
Information provided by (Responsible Party):
Jianguo He, Cardiovascular Institute & Fuwai Hospital
ClinicalTrials.gov Identifier:
NCT00615823
First received: February 4, 2008
Last updated: February 22, 2012
Last verified: February 2012
History of Changes
  Purpose

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 Intervention Phase
Hypertension, Pulmonary
 Drug: Atorvastatin
Drug: Placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Cardiovascular Institute & Fuwai Hospital:

Primary Outcome Measures:
  • The placebo-corrected change from baseline to week 24 in 6-minute walk distance [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time from randomization to clinical worsening [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
    Clinical worsening was defined as death, the first occurrence of hospitalization for pulmonary arterial hypertension, or initiation of PAH-specific drug therapy

  • Change from baseline to week 24 in World Health Organization functional class [ Time Frame: measured at 6 monthes ] [ Designated as safety issue: No ]
    World Health Organization (WHO) functional class: an adaptation of the New York Heart Association classification.

  • Change from baseline to week 24 in Borg dyspnea score [ Time Frame: measured at 6 monthes ] [ Designated as safety issue: No ]
    Borg dyspnea score: with 0 representing no dyspnea and 10 maximal dyspnea.

  • Change from baseline to week 24 in hemodynamic parameters derived from right heart catheterization. [ Time Frame: measured at 6 monthes ] [ Designated as safety issue: No ]
    Hemodynamic parameters: mean pulmonary artery pressure, right atrial pressure, cardiac index and pulmonary vascular resistance.


Enrollment: 220
Study Start Date: February 2007
Study Completion Date: May 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00615823

Locations
China, Beijing
Cardiovascular Institute and Fu Wai Hospital
Beijing, Beijing, China, 100037
Sponsors and Collaborators
Cardiovascular Institute & Fuwai Hospital
National Grant from The Ministry of Science and Technology
Capital Development Scientific Fund
Investigators
Study Chair: Jianguo He, MD Cardiovascular Institute & Fuwai Hospital
  More Information

No publications provided by Cardiovascular Institute & Fuwai Hospital

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

Responsible Party: Jianguo He, Professor, Cardiovascular Institute & Fuwai Hospital
ClinicalTrials.gov Identifier: NCT00615823     History of Changes
Other Study ID Numbers: 2006-1152, 2006BAI01A07, 2005-1018
Study First Received: February 4, 2008
Last Updated: February 22, 2012
Health Authority: China: Ministry of Health
China: The Ministry of Science and Technology

Keywords provided by Cardiovascular Institute & Fuwai Hospital:
Pulmonary Arterial Hypertension

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
 Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2013