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Atorvastatin in Pulmonary Hypertension (APATH)

Primary Purpose

Hypertension, Pulmonary

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Atorvastatin

Placebo

About this trial

This is an interventional treatment trial for Hypertension, Pulmonary focused on measuring Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Cardiovascular Institute and Fu Wai Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm Description

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

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

Outcomes

Primary Outcome Measures

The placebo-corrected change from baseline to week 24 in 6-minute walk distance

Secondary Outcome Measures

Time from randomization to clinical worsening

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

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

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.

Hemodynamic parameters: mean pulmonary artery pressure, right atrial pressure, cardiac index and pulmonary vascular resistance.

Full Information

NCT ID

NCT00615823

First Posted

February 4, 2008

Last Updated

February 22, 2012

Sponsor

Chinese Academy of Medical Sciences, Fuwai Hospital

Collaborators

National Grant from The Ministry of Science and Technology, Capital Development Scientific Fund

1. Study Identification

Unique Protocol Identification Number

NCT00615823

Brief Title

Atorvastatin in Pulmonary Hypertension

Acronym

APATH

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

2. Study Status

Record Verification Date

February 2012

Overall Recruitment Status

Completed

Study Start Date

February 2007 (undefined)

Primary Completion Date

March 2010 (Actual)

Study Completion Date

May 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese Academy of Medical Sciences, Fuwai Hospital

Collaborators

National Grant from The Ministry of Science and Technology, Capital Development Scientific Fund

4. Oversight

Data Monitoring Committee

Yes

5. 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypertension, Pulmonary

Keywords

Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

220 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

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

Arm Title

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Atorvastatin

Other Intervention Name(s)

atorvastatin: a'le(bland names)

Intervention Description

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

Intervention Name(s)

Placebo

Other Intervention Name(s)

matching placebo: a'le(brand name)

Intervention Description

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.

Primary Outcome Measure Information:

Title

The placebo-corrected change from baseline to week 24 in 6-minute walk distance

Time Frame

Measured at 6 months

Secondary Outcome Measure Information:

Title

Time from randomization to clinical worsening

Description

Clinical worsening was defined as death, the first occurrence of hospitalization for pulmonary arterial hypertension, or initiation of PAH-specific drug therapy

Time Frame

Measured at 6 months

Title

Change from baseline to week 24 in World Health Organization functional class

Description

World Health Organization (WHO) functional class: an adaptation of the New York Heart Association classification.

Time Frame

measured at 6 monthes

Title

Change from baseline to week 24 in Borg dyspnea score

Description

Borg dyspnea score: with 0 representing no dyspnea and 10 maximal dyspnea.

Time Frame

measured at 6 monthes

Title

Change from baseline to week 24 in hemodynamic parameters derived from right heart catheterization.

Description

Hemodynamic parameters: mean pulmonary artery pressure, right atrial pressure, cardiac index and pulmonary vascular resistance.

Time Frame

measured at 6 monthes

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jianguo He, MD

Organizational Affiliation

Chinese Academy of Medical Sciences, Fuwai Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Cardiovascular Institute and Fu Wai Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100037

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

22362846

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.

Results Reference

derived

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Atorvastatin in Pulmonary Hypertension

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