A Phase 2 Study to Determine the Safety and Efficacy of AIR001 in Subjects With Pulmonary Arterial Hypertension (PAH)
2014年4月7日 更新者：Aires Pharmaceuticals, Inc.
A Phase 2, Multi-Center, Open-label, Randomized, Parallel-Dose Study to Determine the Safety and Efficacy of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension (PAH)
The purpose of this study is to evaluate the safety and effectiveness of an investigational/experimental drug called AIR001.
To test the effectiveness, the study will evaluate how AIR001 affects the blood vessels in the lungs and the function of the heart. This will be done by monitoring changes in Pulmonary Vascular Resistance (PVR); from Baseline/Day 1 (start of study drug) to Week 16 of the study. PVR measures the resistance to flow in the blood vessels of the lungs. The study will include other assessments to evaluate the effect of the study drug on PAH, including measurements of exercise ability and evaluations of PAH disease symptoms.
調査の概要
詳細な説明
The primary objective of this study is to evaluate the efficacy of inhaled nebulized AIR001 administered, for 16 weeks, according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH), as determined by change in Pulmonary Vascular Resistance (PVR) from Baseline to Week 16 measured immediately post completion of AIR001 nebulization (as soon as feasible).
研究の種類
介入
入学 (実際)
29
段階
- フェーズ2
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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California
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La Jolla、California、アメリカ、92037
- UCSD Medical Center
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Torrance、California、アメリカ、90509
- UCLA Medical Center
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Colorado
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Aurora、Colorado、アメリカ、80045
- University of Colorado Denver
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Kentucky
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Louisville、Kentucky、アメリカ、40202
- Kentuckiana Pulmonary Associates
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Maryland
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Baltimore、Maryland、アメリカ、21201
- University of Maryland Medical Center
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Massachusetts
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Boston、Massachusetts、アメリカ、02115
- Brigham and Women's Hospital
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Boston、Massachusetts、アメリカ、02111
- Tufts Medical Center
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Boston、Massachusetts、アメリカ、02118
- Boston University School of Medicine
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Missouri
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St. Louis、Missouri、アメリカ、63110-1093
- Washington University School of Medicine
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North Carolina
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Durham、North Carolina、アメリカ、27710
- Duke University Medical Center
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Ohio
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Cincinnati、Ohio、アメリカ、45267
- University of Cincinnati
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Columbus、Ohio、アメリカ、43210
- The Ohio State University Medical Center
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15213
- University of Pittsburgh Medical Center
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Texas
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Dallas、Texas、アメリカ、75390
- University of Texas Southwestern Medical Center
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Houston、Texas、アメリカ、77030
- Baylor College of Medicine
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Virginia
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Falls Church、Virginia、アメリカ、22042
- Inova Fairfax Hospital
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Wisconsin
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Milwaukee、Wisconsin、アメリカ、53215
- Aurora St. Luke's Medical Center
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New South Wales
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Darlinghurst、New South Wales、オーストラリア、2010
- St. Vincent's Hospital
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Queensland
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Chermside、Queensland、オーストラリア、4032
- The Prince Charles Hospital
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Tasmania
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Hobart、Tasmania、オーストラリア、7000
- Royal Hobart Hospital
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Victoria
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Melbourne、Victoria、オーストラリア、3004
- The Alfred Hospital
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Budapest、ハンガリー、1083
- Gottsegen Gyorgy Hungarian
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Budapest、ハンガリー、1125
- Semmelweis Karlocai
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Debrecen、ハンガリー、4032
- University of Debrecen
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Szeged、ハンガリー、6720
- University of Szeged
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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
18年～75年 (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
Inclusion Criteria:
- Signed and dated informed consent document
- Able to comply with study procedures
Diagnosis of PAH as classified by:
- Idiopathic (IPAH) or heritable(HPAH); or
- PAH associated with CTD; Systemic Sclerosis, Limited Scleroderma, Mixed, SLE, or overlap syndrome;
- PAH associated with HIV ii. Simple, congenital shunts at least one year post repair. iii. Exposure to legal drugs, chemicals and toxins
Cardiac catheterization prior to Screening with:
- mPAP ≥ 25 mmHg (at rest);
- PCWP ≤ 15 mmHg; and
- PVR > 3 mmHg/L/min or 240 dyn.sec/cm5
A qualification cardiac catheterization, to confirm the persistence and severity of PAH, if the diagnostic catheterization was performed more than 30 days prior to Baseline
- Confirms diagnosis;
- PVR above 300 dyn.sec/cm5 to demonstrate the persistence and severity of PAH; and
- No change in disease-specific PAH therapy since the qualification catheterization used
- Newly diagnosed PAH on no disease-specific PAH therapy or previously diagnosed on oral disease-specific PAH therapy for 90 days prior with either an ETRA and/or PDE-5i
Has PFTs within 180 days prior to Baseline with no evidence of significant parenchymal lung disease defined as:
- FEV1 ≤ 70% (predicted) (pre-bronchodilators);
- FEV1/FVC ≤ 70% (pre-bronchodilators); or
- Total lung capacity < 70% (predicted).
- Has WHO/NYHA FC II- IV.
- ≥ 18 and ≤ 75 years.
- Weight ≥ 40 kg.
- Has 6MWT distance at least 50 meters.
- Had a V/Q scan or pulmonary angiogram prior to Screening that shows no evidence of thromboembolic disease
- If on the following: vasodilators (including calcium channel blockers), digoxin, spironolactone, or L-Arginine; must be on a stable dose 30 days prior to Baseline and maintained throughout the study
- If on corticosteroids, has been receiving a stable dose of ≤ 20 mg/day of prednisone (or equivalent dose, if other corticosteroid) for at least 30 days
- Women of childbearing potential must be using at least one form of medically acceptable contraception. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential. Men who are not sterile must also agree to use contraception
Exclusion Criteria:
- Participation in a device or other interventional clinical studies, within 30 days of Baseline and during study participation
- Participation in a cardio-pulmonary rehabilitation program based upon exercise within 30 days prior to Baseline and/or during the study
- Has uncontrolled systemic hypertension: SBP > 160 millimeter of mercury (mmHg) or DBP > 100 mmHg during Screening
- SBP < 90 mmHg at Screening or Baseline
- History of orthostatic hypotension or at the time of Screening; defined as a drop in SBP by ≥ 20 mmHg or DBP of ≥ 10 mmHg during Screening
History of left-sided heart disease and/or clinically significant cardiac disease, including:
- Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild;
- Pericardial constriction;
- Restrictive or congestive cardiomyopathy;
- Left ventricular ejection fraction < 40%
- Left ventricular shortening fraction < 22% by ECHO prior to Screening;
- Symptomatic coronary disease
- Significant (2+ for regurgitation) valvular disease other than TR or PR
- Acutely decompensated heart failure within 30 days prior to Baseline
- History of atrial septostomy within 180 days prior to Baseline
- History of obstructive sleep apnea (treated, untreated or resolved)
- Diagnosis of Down syndrome
- Moderate to severe hepatic impairment
- Has chronic renal insufficiency as defined by serum creatinine > 2.5 mg/dL or has an eGFR < 30 mL/min at Screening, or requires dialysis
- Has a Hgb concentration < 8.5 g/dL at Screening
Personal or family history of the following:
- Congenital or acquired methemoglobinemia;
- RBC CYPB5 reductase deficiency
- G6PD deficiency or any contraindication to receiving methylene blue
For subjects with HIV any of the following:
- Concomitant active opportunistic infections 180 days prior to Screening;
- Detectable viral load within 90 days of Screening;
- T-cell count < 200 mm3 within 90 days of Screening;
- Changes in antiretroviral regimen within 90 days of Screening;
- Using inhaled pentamidine
- Receiving chronic treatment with prostacyclin/prostacyclin analogue within 60 days of Baseline
- Requirement of intravenous inotropes within 30 days prior to Baseline
- The use of oral or topical nitrates (nitroglycerin, glyceryl trinitrate (GTN), isosorbide dinitrate, and isosorbide mononitrate) within 30 days prior to Baseline and until EOS or Termination
- Known or suspected hypersensitivity or allergic reaction to sodium nitrite or sodium nitrate
- History of malignancy within 5-years prior to Baseline
- Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation
- Has a disorder that compromises the ability to give informed consent
- Is currently pregnant or breastfeeding or intends to become pregnant
- Investigators, study staff or their immediate families
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：なし（オープンラベル）
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：80mg AIR001 four times daily
80mg AIR001 nebulized four times daily for 16 weeks
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Dose arms specify dose loaded into the I-neb AAD System nebulizer
他の名前：
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実験的：46mg AIR001 four times daily
46mg AIR001 nebulized four times daily for 16 weeks
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Dose arms specify dose loaded into the I-neb AAD System nebulizer
他の名前：
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実験的：80mg AIR001 once daily
80mg AIR001 nebulized once daily for 16 weeks
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Dose arms specify dose loaded into the I-neb AAD System nebulizer
他の名前：
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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 |
|---|---|---|
|
Change in pulmonary vascular resistance (PVR)from baseline to week 16 assessed at peak AIR001
時間枠：16 weeks
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The primary objective of this study is to evaluate the efficacy of inhaled nebulized AIR001 administered, for 16 weeks, according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH), as determined by change in Pulmonary Vascular Resistance (PVR) from Baseline to Week 16 measured immediately post completion of AIR001 nebulization (as soon as feasible).
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16 weeks
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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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Time to Clinical Worsening (TTCW), other hemodynamics, and safety
時間枠：16 weeks
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To evaluate the effect of inhaled nebulized AIR001 administered according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with WHO Group 1 PAH for 16 weeks, as determined by time to the first morbidity/mortality event as defined in Time to Clinical Worsening (TTCW) assessments and change from Baseline to Week 16 in the following: Pulmonary Vascular Resistance Index (PVRI), N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP), 6-Minute Walk Distance (6MWD) assessed at peak, 6MWD assessed prior to AIR001 nebulization (trough), Cardiac Output (CO), Cardiac Index (CI), Mean Right Atrial Pressure (mRAP), WHO/NYHA Functional Class (FC), Quality of Life (QOL) as measured by Short-Form 36 (SF-36), Borg Dyspnea Index, Mean pulmonary artery pressure (mPAP), PVR measured at trough, PVR/systemic vascular resistance (SVR) ratio at trough and peak, To evaluate the safety and tolerability of AIR001 in subjects with WHO Group 1 PAH. |
16 weeks
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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。
捜査官
- 主任研究者：Adaani E Frost, M.D.、Baylor College of Medicine
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available. Erratum In: Am J Respir Crit Care Med. 2016 May 15;193(10):1185.
- Chaouat A, Bugnet AS, Kadaoui N, Schott R, Enache I, Ducolone A, Ehrhart M, Kessler R, Weitzenblum E. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005 Jul 15;172(2):189-94. doi: 10.1164/rccm.200401-006OC. Epub 2005 Apr 14.
- Gladwin MT, Vichinsky E. Pulmonary complications of sickle cell disease. N Engl J Med. 2008 Nov 20;359(21):2254-65. doi: 10.1056/NEJMra0804411. No abstract available.
- Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon RO 3rd, Gladwin MT. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med. 2003 Dec;9(12):1498-505. doi: 10.1038/nm954. Epub 2003 Nov 2.
- McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009 Apr 28;53(17):1573-619. doi: 10.1016/j.jacc.2009.01.004. No abstract available.
- Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med. 2004 Oct 14;351(16):1655-65. doi: 10.1056/NEJMra035488. No abstract available.
- Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol (1985). 2009 Oct;107(4):1144-55. doi: 10.1152/japplphysiol.00722.2009. Epub 2009 Aug 6.
- Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf). 2007 Sep;191(1):59-66. doi: 10.1111/j.1748-1716.2007.01713.x. Epub 2007 Jul 17.
- Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise. Free Radic Biol Med. 2010 Jan 15;48(2):342-7. doi: 10.1016/j.freeradbiomed.2009.11.006. Epub 2009 Nov 12.
- Lansley KE, Winyard PG, Bailey SJ, Vanhatalo A, Wilkerson DP, Blackwell JR, Gilchrist M, Benjamin N, Jones AM. Acute dietary nitrate supplementation improves cycling time trial performance. Med Sci Sports Exerc. 2011 Jun;43(6):1125-31. doi: 10.1249/MSS.0b013e31821597b4.
- Larsen FJ, Schiffer TA, Borniquel S, Sahlin K, Ekblom B, Lundberg JO, Weitzberg E. Dietary inorganic nitrate improves mitochondrial efficiency in humans. Cell Metab. 2011 Feb 2;13(2):149-59. doi: 10.1016/j.cmet.2011.01.004.
- Piazza G, Goldhaber SZ. Chronic thromboembolic pulmonary hypertension. N Engl J Med. 2011 Jan 27;364(4):351-60. doi: 10.1056/NEJMra0910203. No abstract available.
- Vanhatalo A, Fulford J, Bailey SJ, Blackwell JR, Winyard PG, Jones AM. Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia. J Physiol. 2011 Nov 15;589(Pt 22):5517-28. doi: 10.1113/jphysiol.2011.216341. Epub 2011 Sep 12.
- Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004 Sep 30;351(14):1425-36. doi: 10.1056/NEJMra040291. No abstract available.
- Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing ZC, Krowka MJ, Langleben D, Nakanishi N, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S43-S54. doi: 10.1016/j.jacc.2009.04.012.
- Ranque B, Authier FJ, Berezne A, Guillevin L, Mouthon L. Systemic sclerosis-associated myopathy. Ann N Y Acad Sci. 2007 Jun;1108:268-82. doi: 10.1196/annals.1422.029.
- Opravil M, Pechere M, Speich R, Joller-Jemelka HI, Jenni R, Russi EW, Hirschel B, Luthy R. HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study. Am J Respir Crit Care Med. 1997 Mar;155(3):990-5. doi: 10.1164/ajrccm.155.3.9117037.
- Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC); European Respiratory Society (ERS); International Society of Heart and Lung Transplantation (ISHLT); Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009 Dec;34(6):1219-63. doi: 10.1183/09031936.00139009. Epub 2009 Sep 12. No abstract available.
- Ahanchi SS, Tsihlis ND, Kibbe MR. The role of nitric oxide in the pathophysiology of intimal hyperplasia. J Vasc Surg. 2007 Jun;45 Suppl A:A64-73. doi: 10.1016/j.jvs.2007.02.027.
- Alef MJ, Vallabhaneni R, Carchman E, Morris SM Jr, Shiva S, Wang Y, Kelley EE, Tarpey MM, Gladwin MT, Tzeng E, Zuckerbraun BS. Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats. J Clin Invest. 2011 Apr;121(4):1646-56. doi: 10.1172/JCI44079. Epub 2011 Mar 23.
- Badesch DB, Champion HC, Gomez Sanchez MA, Hoeper MM, Loyd JE, Manes A, McGoon M, Naeije R, Olschewski H, Oudiz RJ, Torbicki A. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S55-S66. doi: 10.1016/j.jacc.2009.04.011.
- Barbosa PB, Ferreira EM, Arakaki JS, Takara LS, Moura J, Nascimento RB, Nery LE, Neder JA. Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension. Eur J Appl Physiol. 2011 Aug;111(8):1851-61. doi: 10.1007/s00421-010-1799-6. Epub 2011 Jan 12.
- Battistini B, Berthiaume N, Kelland NF, Webb DJ, Kohan DE. Profile of past and current clinical trials involving endothelin receptor antagonists: the novel "-sentan" class of drug. Exp Biol Med (Maywood). 2006 Jun;231(6):653-95.
- Battle RW, Davitt MA, Cooper SM, Buckley LM, Leib ES, Beglin PA, Tischler MD. Prevalence of pulmonary hypertension in limited and diffuse scleroderma. Chest. 1996 Dec;110(6):1515-9. doi: 10.1378/chest.110.6.1515.
- Bergstra A, van den Heuvel AF, Zijlstra F, Berger RM, Mook GA, van Veldhuisen DJ. Validation of Fick cardiac output calculated with assumed oxygen consumption: a study of cardiac output during epoprostenol. Neth Heart J. 2004 May;12(5):208-213.
- Channick RN, Olschewski H, Seeger W, Staub T, Voswinckel R, Rubin LJ. Safety and efficacy of inhaled treprostinil as add-on therapy to bosentan in pulmonary arterial hypertension. J Am Coll Cardiol. 2006 Oct 3;48(7):1433-7. doi: 10.1016/j.jacc.2006.05.070. Epub 2006 Sep 14.
- Clozel M, Breu V, Gray GA, Kalina B, Loffler BM, Burri K, Cassal JM, Hirth G, Muller M, Neidhart W, et al. Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist. J Pharmacol Exp Ther. 1994 Jul;270(1):228-35.
- Dejam A, Hunter CJ, Tremonti C, Pluta RM, Hon YY, Grimes G, Partovi K, Pelletier MM, Oldfield EH, Cannon RO 3rd, Schechter AN, Gladwin MT. Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation. Circulation. 2007 Oct 16;116(16):1821-31. doi: 10.1161/CIRCULATIONAHA.107.712133. Epub 2007 Sep 24.
- Ghofrani HA, Barst RJ, Benza RL, Champion HC, Fagan KA, Grimminger F, Humbert M, Simonneau G, Stewart DJ, Ventura C, Rubin LJ. Future perspectives for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S108-S117. doi: 10.1016/j.jacc.2009.04.014.
- Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med. 1995 Jul 27;333(4):214-21. doi: 10.1056/NEJM199507273330403.
- Gielis JF, Lin JY, Wingler K, Van Schil PE, Schmidt HH, Moens AL. Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders. Free Radic Biol Med. 2011 Apr 1;50(7):765-76. doi: 10.1016/j.freeradbiomed.2010.12.018. Epub 2010 Dec 21.
- Gladwin MT, Raat NJ, Shiva S, Dezfulian C, Hogg N, Kim-Shapiro DB, Patel RP. Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation. Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2026-35. doi: 10.1152/ajpheart.00407.2006. Epub 2006 Jun 23.
- Hassoun PM, Mouthon L, Barbera JA, Eddahibi S, Flores SC, Grimminger F, Jones PL, Maitland ML, Michelakis ED, Morrell NW, Newman JH, Rabinovitch M, Schermuly R, Stenmark KR, Voelkel NF, Yuan JX, Humbert M. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S10-S19. doi: 10.1016/j.jacc.2009.04.006.
- Hassoun PM. Pulmonary arterial hypertension complicating connective tissue disease. In: Humbert, M, Lynch JP, Eds. Pulmonary Hypertension. New York: Informa Healthcare USA, Inc. 2010: 161-175
- Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):13S-24S. doi: 10.1016/j.jacc.2004.02.029.
- Hunter CJ, Dejam A, Blood AB, Shields H, Kim-Shapiro DB, Machado RF, Tarekegn S, Mulla N, Hopper AO, Schechter AN, Power GG, Gladwin MT. Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator. Nat Med. 2004 Oct;10(10):1122-7. doi: 10.1038/nm1109. Epub 2004 Sep 12.
- Kiowski W, Sutsch G, Hunziker P, Muller P, Kim J, Oechslin E, Schmitt R, Jones R, Bertel O. Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure. Lancet. 1995 Sep 16;346(8977):732-6. doi: 10.1016/s0140-6736(95)91504-4.
- Krowka MJ, Swanson KL, Frantz RP, McGoon MD, Wiesner RH. Portopulmonary hypertension: Results from a 10-year screening algorithm. Hepatology. 2006 Dec;44(6):1502-10. doi: 10.1002/hep.21431.
- Levi, DS, Scott V, et al. Pulmonary arterial hypertension in congenital heart disease. In: Humbert, M, Lynch, JP, Eds. Pulmonary Hypertension. New York: Informa Healthcare USA, Inc. 2010: 176-195.
- Mainguy V, Maltais F, Saey D, Gagnon P, Martel S, Simon M, Provencher S. Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension. Thorax. 2010 Feb;65(2):113-7. doi: 10.1136/thx.2009.117168. Epub 2009 Aug 30.
- Mehta NJ, Khan IA, Mehta RN, Sepkowitz DA. HIV-Related pulmonary hypertension: analytic review of 131 cases. Chest. 2000 Oct;118(4):1133-41. doi: 10.1378/chest.118.4.1133.
- Morrell NW, Adnot S, Archer SL, Dupuis J, Lloyd Jones P, MacLean MR, McMurtry IF, Stenmark KR, Thistlethwaite PA, Weissmann N, Yuan JX, Weir EK. Cellular and molecular basis of pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S20-S31. doi: 10.1016/j.jacc.2009.04.018.
- Mukerjee D, St George D, Coleiro B, Knight C, Denton CP, Davar J, Black CM, Coghlan JG. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis. 2003 Nov;62(11):1088-93. doi: 10.1136/ard.62.11.1088.
- Olschewski H, Rohde B, Behr J, Ewert R, Gessler T, Ghofrani HA, Schmehl T. Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension. Chest. 2003 Oct;124(4):1294-304. doi: 10.1378/chest.124.4.1294.
- Pluta RM, Dejam A, Grimes G, Gladwin MT, Oldfield EH. Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage. JAMA. 2005 Mar 23;293(12):1477-84. doi: 10.1001/jama.293.12.1477.
- Pluta RM, Oldfield EH, Bakhtian KD, Fathi AR, Smith RK, Devroom HL, Nahavandi M, Woo S, Figg WD, Lonser RR. Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers. PLoS One. 2011 Jan 10;6(1):e14504. doi: 10.1371/journal.pone.0014504.
- Rubin LJ. Primary pulmonary hypertension. N Engl J Med. 1997 Jan 9;336(2):111-7. doi: 10.1056/NEJM199701093360207. No abstract available.
- Rubin LJ; American College of Chest Physicians. Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004 Jul;126(1 Suppl):7S-10S. doi: 10.1378/chest.126.1_suppl.7S. No abstract available.
- Shiva S. Mitochondria as metabolizers and targets of nitrite. Nitric Oxide. 2010 Feb 15;22(2):64-74. doi: 10.1016/j.niox.2009.09.002. Epub 2009 Sep 27.
- Shorr AF, Helman DL, Davies DB, Nathan SD. Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics. Eur Respir J. 2005 May;25(5):783-8. doi: 10.1183/09031936.05.00083404.
- Sitbon O, Lascoux-Combe C, Delfraissy JF, Yeni PG, Raffi F, De Zuttere D, Gressin V, Clerson P, Sereni D, Simonneau G. Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med. 2008 Jan 1;177(1):108-13. doi: 10.1164/rccm.200704-541OC. Epub 2007 Oct 11.
- Smith AP, Demoncheaux EA, Higenbottam TW. Nitric oxide gas decreases endothelin-1 mRNA in cultured pulmonary artery endothelial cells. Nitric Oxide. 2002 Mar;6(2):153-9. doi: 10.1006/niox.2001.0400.
- Souza R, Humbert M, Sztrymf B, Jais X, Yaici A, Le Pavec J, Parent F, Herve P, Soubrier F, Sitbon O, Simonneau G. Pulmonary arterial hypertension associated with fenfluramine exposure: report of 109 cases. Eur Respir J. 2008 Feb;31(2):343-8. doi: 10.1183/09031936.00104807. Epub 2007 Oct 24. Erratum In: Eur Respir J. 2008 Apr;31(4):912.
- Tsihlis ND, Oustwani CS, Vavra AK, Jiang Q, Keefer LK, Kibbe MR. Nitric oxide inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia by increasing the ubiquitination and degradation of UbcH10. Cell Biochem Biophys. 2011 Jun;60(1-2):89-97. doi: 10.1007/s12013-011-9179-3.
- Tyvaso US Package Insert. Research Triangle Park, NC: United Therapeutics Corp; 2011.
- Uhlmann D, Ludwig S, Escher E, Armann B, Gabel G, Teupser D, Tannapfel A, Hauss J, Witzigmann H. Protective effect of a selective endothelin a receptor antagonist (BSF 208075) on graft pancreatitis in pig pancreas transplantation. Transplant Proc. 2001 Nov-Dec;33(7-8):3732-4. doi: 10.1016/s0041-1345(01)02523-4. No abstract available.
- Voswinckel R, Enke B, Reichenberger F, Kohstall M, Kreckel A, Krick S, Gall H, Gessler T, Schmehl T, Ghofrani HA, Schermuly RT, Grimminger F, Rubin LJ, Seeger W, Olschewski H. Favorable effects of inhaled treprostinil in severe pulmonary hypertension: results from randomized controlled pilot studies. J Am Coll Cardiol. 2006 Oct 17;48(8):1672-81. doi: 10.1016/j.jacc.2006.06.062. Epub 2006 Sep 26.
- Ware, JE, Kosinski, M, Dewey JE. How to Score Version Two of the SF-36 Health Survey. Lincoln, RI: QualityMetric, Incorporated, 2000.
- Weber C, Schmitt R, Birnboeck H, Hopfgartner G, van Marle SP, Peeters PA, Jonkman JH, Jones CR. Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects. Clin Pharmacol Ther. 1996 Aug;60(2):124-37. doi: 10.1016/S0009-9236(96)90127-7.
- Weitzenblum E, Chaouat A. Severe pulmonary hypertension in COPD: is it a distinct disease? Chest. 2005 May;127(5):1480-2. doi: 10.1378/chest.127.5.1480. No abstract available.
- Williamson DJ, Wallman LL, Jones R, Keogh AM, Scroope F, Penny R, Weber C, Macdonald PS. Hemodynamic effects of Bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension. Circulation. 2000 Jul 25;102(4):411-8. doi: 10.1161/01.cir.102.4.411.
- Zuckerbraun BS, George P, Gladwin MT. Nitrite in pulmonary arterial hypertension: therapeutic avenues in the setting of dysregulated arginine/nitric oxide synthase signalling. Cardiovasc Res. 2011 Feb 15;89(3):542-52. doi: 10.1093/cvr/cvq370. Epub 2010 Dec 22.
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
2012年11月1日
一次修了 (実際)
2014年2月1日
研究の完了 (実際)
2014年2月1日
試験登録日
最初に提出
2012年11月8日
QC基準を満たした最初の提出物
2012年11月9日
最初の投稿 (見積もり)
2012年11月12日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年4月9日
QC基準を満たした最後の更新が送信されました
2014年4月7日
最終確認日
2014年4月1日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- AIR001-CS05
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