Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1) (ATHENA-1)
2012年6月22日 更新者：Gilead Sciences
An Open-label, Multicenter Study of Ambrisentan and a Phosphodiesterase Type-5 Inhibitor Combination Therapy in Subjects With Pulmonary Arterial Hypertension Who Have Demonstrated a Sub-Optimal Response to a Phosphodiesterase Type-5 Inhibitor
To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy.
The study was originally designed as a 2-arm, double-blind, randomized study in which patients received ambrisentan or placebo for 24 weeks, and then received ambrisentan blinded to dose for 24 weeks. With Protocol Amendment 2 (12 June, 2009), the study was switched to single-arm, open-label treatment, and all patients remaining in the placebo arm were switched to open-label ambrisentan treatment. Patients who enrolled after Amendment 2 all received open-label ambrisentan.
調査の概要
詳細な説明
The primary objective of this study is to evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy.
The secondary objectives of this study are to evaluate the change from baseline in other clinical measures of PAH following the addition of ambrisentan to background PDE-5i therapy in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy.
The safety and tolerability of ambrisentan/PDE-5i combination therapy will be evaluated throughout the study. In addition, long-term efficacy will be examined.
研究の種類
介入
入学 (実際)
38
段階
- フェーズ 4
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Alabama
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Mobile、Alabama、アメリカ、36617
- University Of South Alabama
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Arizona
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Phoenix、Arizona、アメリカ、85013
- Arizona Pulmonary Specialists
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California
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Los Angeles、California、アメリカ、90073
- West Los Angeles Healthcare Center
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Torrance、California、アメリカ、90502
- Harbor - UCLA
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Florida
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Ft. Lauderdale、Florida、アメリカ、33331
- Cleveland Clinic
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Gainesville、Florida、アメリカ、32610
- University of Florida
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Miami Beach、Florida、アメリカ、33140
- Mount Sinai Medical Center
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Orlando、Florida、アメリカ、32806
- Orlando Heart Center
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Georgia
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Atlanta、Georgia、アメリカ、30322
- Emory University
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Decatur、Georgia、アメリカ、30030
- Atlanta Institute for Medical Research
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Iowa
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Iowa City、Iowa、アメリカ、52242
- University of Iowa
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Maryland
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Baltimore、Maryland、アメリカ、21201
- University of Maryland
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Massachusetts
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Boston、Massachusetts、アメリカ、02115
- Brigham & Women's Hospital
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Boston、Massachusetts、アメリカ、02115
- BACH Cardiology
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Michigan
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Detroit、Michigan、アメリカ、48201
- Wayne State University
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Minnesota
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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic
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New York
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New York、New York、アメリカ、10021
- Weill Cornell Medical Center
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North Carolina
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Asheville、North Carolina、アメリカ、28803
- Asheville Cardiology Associates
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Chapel Hill、North Carolina、アメリカ、27599
- University of North Carolina at Chapel Hill
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Ohio
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Cincinnati、Ohio、アメリカ、45219
- The Lindner Clinical Trial Center
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Cleveland、Ohio、アメリカ、44106
- University Hospitals of Cleveland
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Columbus、Ohio、アメリカ、43210
- Ohio State University
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Pennsylvania
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Duncansville、Pennsylvania、アメリカ、16635
- Altoona Center for Clinical Research
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Pittsburgh、Pennsylvania、アメリカ、15212
- Allegheny General Hospital
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Pittsburgh、Pennsylvania、アメリカ、15213
- University of Pittsburgh Medical Center
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Rhode Island
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Providence、Rhode Island、アメリカ、02903
- Rhode Island Hospital
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Texas
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Dallas、Texas、アメリカ、75235
- UT Southwestern Medical Center
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Houston、Texas、アメリカ、77030
- Baylor College of Medicine
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Temple、Texas、アメリカ、76508
- Scott & White Memorial Hospital
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Virginia
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Norfolk、Virginia、アメリカ、23507
- Sentara Norfolk General Hospital
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
16年～75年 (子、大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Selected Inclusion Criteria
- Must be between 16 and 75 years of age;
- Must weigh at least 40 kg;
- Have a current diagnosis of idiopathic PAH, familial PAH, or PAH that is primarily due to connective tissue disease, congenital heart defects, drug or toxin use, or human immunodeficiency virus (HIV);
- Have WHO functional class III symptoms;
- Be receiving sildenafil or tadalafil monotherapy for the treatment of PAH for at least the past 12 weeks and at a stable dose for at least 8 consecutive weeks;
- Meet all of the following hemodynamic criteria by means of a right heart catheterization: mPAP of at least 25 mmHg; PVR of at least 400 dyne*sec/cm5; pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of not more than 15 mmHg;
- Meet all of the following pulmonary function test criteria no more than 12 weeks before the screening visit: total lung capacity at least 60% of predicted normal and forced expiratory volume in 1 second of at least 65% of predicted normal;
- Able to walk at least 150 meters during the screening 6-minute walk test (6MWT);
- If receiving calcium channel blockers or 5-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (i.e., statins) must be on stable therapy for at least 4 weeks;
- If diagnosed with HIV, must have stable disease status.
Selected Exclusion Criteria:
- Have a current pulmonary hypertension diagnosis other than idiopathic PAH, familial PAH, or PAH that is primarily due to connective tissue disease, congenital heart defects, drug or toxin use, or HIV;
- Have left ventricular ejection fraction (LVEF) ≤40% or clinically significant ischemic, valvular, or constrictive heart disease;
- Have received chronic prostanoid or endothelin receptor antagonist (ERA) therapy (eg, bosentan, sitaxsentan) within the past 12 weeks;
- Have discontinued ERA treatment for any adverse reaction other than those associated with liver function test abnormalities;
- Have received IV inotropes within 2 weeks;
- Have a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is greater than 2.0x the upper limit of normal.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Ambrisentan
Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i; sildenafil or tadalafil).
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Ambrisentan was administered orally once daily; dose level was 5 mg for the first 4 weeks, followed by 10 mg for the remainder of the study; ambrisentan was supplied as 5-mg and 10-mg tablets.
他の名前：
Sildenafil was administered at the dose previously established for each subject (20-100 mg) orally three times daily.
Sildenafil was supplied as 20-mg tablets, or formulated as sildenafil citrate in 25-, 50-, or 100-mg tablets.
他の名前：
Tadalafil was administered at the dose previously established for each subject (not to exceed 40 mg per day) orally once daily.
Tadalafil was supplied as 20-mg tablets.
他の名前：
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アクティブコンパレータ：Placebo
Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (sildenafil or tadalafil).
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Sildenafil was administered at the dose previously established for each subject (20-100 mg) orally three times daily.
Sildenafil was supplied as 20-mg tablets, or formulated as sildenafil citrate in 25-, 50-, or 100-mg tablets.
他の名前：
Tadalafil was administered at the dose previously established for each subject (not to exceed 40 mg per day) orally once daily.
Tadalafil was supplied as 20-mg tablets.
他の名前：
アンブリセンタンに合わせたプラセボを 1 日 1 回経口投与しました。
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)
時間枠：Baseline to Week 24
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The primary objective of this study is to evaluate the change from baseline in PVR, and other hemodynamic parameters, following the addition of ambrisentan to background PDE-5i therapy in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy.
A decrease in measurement value (dynes sec/cm^5) indicates improvement for this patient population.
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Baseline to Week 24
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)
時間枠：Baseline to Week 24
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This secondary hemodynamic outcome is supportive of the primary outcome.
A decrease in measurement value (mmHg) indicates improvement for this patient population.
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Baseline to Week 24
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Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)
時間枠：Baseline to Week 24
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This secondary hemodynamic outcome is supportive of the primary outcome.
A decrease in measurement value (mmHg) indicates improvement for this patient population.
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Baseline to Week 24
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Change From Baseline in Cardiac Output (LOCF)
時間枠：Baseline to Week 24
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This secondary hemodynamic outcome is supportive of the primary outcome.
An increase in measurement value (L/min) indicates improvement for this patient population.
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Baseline to Week 24
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Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
時間枠：Baseline to Week 48
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The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24.
The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated.
An increase in measurement value (meters walked) indicates improvement for this patient population.
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Baseline to Week 48
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Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
時間枠：Baseline to Week 48
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The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24.
The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated.
The dyspnea index measures the degree of breathlessness after completion of the 6MWT using a scale of 0 to 10, with 0 indicating no breathlessness and 10 indicating maximum breathlessness.
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Baseline to Week 48
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Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
時間枠：Baseline to Week 48
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The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24.
The changes from Baseline to Weeks 12, 36, and 48 were also evaluated.
Lower scores and decreases from baseline represent improved functioning and QOL.
The CAMPHOR survey was not assessed at Week 4. The total CAMPHOR score scale ranges from 0 (good) to 25 (poor).
A reduction in score over time represents improvement in this patient population.
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Baseline to Week 48
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Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48.
時間枠：Baseline to Week 48
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The primary analysis of this secondary outcome measure is change from Baseline to Week 24.
The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated.
WHO categories are 1 to 4 with the worst category being 4. Improvement is represented by a change in category to a lower number (for example, change from category 3 to 2), and deterioration is represented by a change in category to a higher number (for example, change from category 2 to 4).
No change is represented by no change in category (for example, category 2 which remains 2).
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Baseline to Week 48
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Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
時間枠：Baseline to Week 48
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The primary analysis of this secondary outcome measure is mean percent change from Baseline to Week 24.
The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated.
A decrease in log-transformed measurement value (pg/mL) indicates improvement for this patient population.
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Baseline to Week 48
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Time to Clinical Worsening of PAH, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48
時間枠：Baseline to Week 48+
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The time to clinical worsening was defined as the time from enrollment to the first occurrence of death, lung transplantation, hospitalization for PAH, atrial septostomy, or initiation of chronic parenteral prostanoid therapy.
Results are presented as the Kaplan-Meier estimate (% probability) of having clinical worsening after a given time.
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Baseline to Week 48+
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Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48
時間枠：Baseline to Week 48+
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Overall survival was defined as the time from initiation of active treatment to death.
Results are presented as the Kaplan-Meier estimate (% probability) of death after a given time.
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Baseline to Week 48+
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2008年4月1日
一次修了 (実際)
2011年2月1日
研究の完了 (実際)
2011年7月1日
試験登録日
最初に提出
2008年2月6日
QC基準を満たした最初の提出物
2008年2月15日
最初の投稿 (見積もり)
2008年2月18日
学習記録の更新
投稿された最後の更新 (見積もり)
2012年7月30日
QC基準を満たした最後の更新が送信されました
2012年6月22日
最終確認日
2012年6月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- GS-US-300-0117
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
Ambrisentanの臨床試験
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West Penn Allegheny Health SystemJohns Hopkins University; University of Colorado, Denver; Massachusetts General Hospital; Mayo Clinic と他の協力者引きこもった