Evaluation and Treatment of Pulmonary Vascular Disease in Moderate to Severe CF
2019年7月12日 更新者:Jennifer Taylor-Cousar、National Jewish Health
Evaluation and Treatment of Pulmonary Vascular Disease in Moderate to Severe Cystic Fibrosis Lung Disease
This study evaluates the ability of the drug sildenafil to improved exercise capacity, cardiac performance during exercise, and quality of life in patients with moderate to severe CF lung disease.
3/4 of the subjects will receive sildenafil and 1/4 will receive placebo.
調査の概要
詳細な説明
Over time, patients with Cystic Fibrosis (CF) develop disabling lung disease that progresses to chronic respiratory failure, exercise intolerance with marked limitation of physical activity, and premature death.
Despite substantial improvements in care, patients with CF often develop pulmonary vascular disease (PVD) that leads to pulmonary hypertension.
Previous studies have clearly linked severe pulmonary hypertension and right heart failure with high mortality in CF.
Early clinical manifestations of PVD prior to the development of cor pulmonale include shortness of breath and dyspnea with exertion, but the extent to which PVD contributes to the decline in exercise tolerance and quality of life in patients with CF is not known.
Early evidence of PVD could be recognized in CF patients through standardized exercise testing and echocardiographic evaluation.
Identifying those CF patients with PVD prior to the onset of right ventricular dysfunction may allow pharmacologic intervention to attenuate the progression of cardiovascular disease and improve quality of life.
Clinical trials have demonstrated that treatment with the phosphodiesterase type 5 inhibitor, sildenafil, can decrease pulmonary vascular resistance and improve exercise tolerance in non-CF patients with pulmonary hypertension.
Because experimental and clinical studies have implicated impaired NO-cGMP signaling in the pathophysiology of lung disease in CF, sildenafil may provide a novel pharmacological approach for treating PVD in patients with CF lung disease.
研究の種類
介入
入学 (実際)
14
段階
- フェーズ2
- フェーズ 1
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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Colorado
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Denver、Colorado、アメリカ、80206
- National Jewish Health
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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年歳以上 (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:
- Confirmed diagnosis of CF based on the following criteria: Positive sweat chloride ≥60mEq/liter (by pilocarpine iontophoresis) and/or Genotype with two identifiable mutations consistent with CF, and accompanied by one or more clinical features consistent with the CF phenotype
- Male or female patients ≥ 18 years of age
- FEV1 ≥ 20% predicted and ≤ 70% predicted (Hankinson)
- Clinically stable without evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the 14 days prior to the screening visit
- Ability to reproducibly perform spirometry (according to ATS criteria)
- Ability to understand and sign a written informed consent or assent and comply with the requirements of the study
- Willingness to maintain chronic CF medication schedule (e.g. alternating month inhaled antibiotics)
Exclusion Criteria:
- History of hypersensitivity to sildenafil
- Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)
- Breastfeeding, pregnant, or verbal expression of unwillingness to practice an acceptable birth control method (abstinence, hormonal or barrier methods, partner sterilization or intrauterine device) during participation in the study for women of child-bearing potential.
- History of significant hepatic disease (AST or ALT > 5 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension),
- History of significant cardiovascular disease (history of aortic stenosis, coronary artery disease, or life-threatening arrhythmia),
- History of severe neurological disease (e.g. history of stroke),
- History of severe hematologic disease (e.g. history of bleeding diathesis; current INR > 2.0
- History of severe ophthalmologic disease (e.g. history of retinal impairment or non-arteritic ischemic optic neuritis)
- History of severe renal impairment (creatinine >1.8 mg/dL.)
- Inability to swallow pills
- Previous organ transplantation
- Use of concomitant nitrates, α-blocker, or Ca channel blocker (currently or within one month of Visit 1)
- Use of concomitant medications known to be potent inhibitors of CYP3A4 [e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin (currently or within one month of initiation of study drug)] NOTE: use of azithromycin is NOT a cause for exclusion
- History of sputum or throat swab culture yielding Burkholderia cepacia or Mycobacterium massiliense within 2 years of screening
- Weight less than 40 kg at Screening
- History of migraine headaches.
- Resting room air oxygen saturation <80% without supplemental oxygen
- Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data
- Start of CFTR modulator therapy less than 1 month prior to first dose of sildenafil or placebo
- Use of anticoagulants
- Frank pulmonary hypertension (RVSP >40 mmHg by ECHO)
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:4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:Sildenafil
Subjects will be randomized in a 3:1 (sildenafil:placebo) fashion.
Subjects randomized to the treatment arm will receive sildenafil 20 mg p.o. t.i.d for 1 week followed by 40 mg p.o. t.i.d. for 11 weeks.
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active sildenafil
他の名前:
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プラセボコンパレーター:Placebo
Subjects randomized to the placebo arm will receive placebo p.o. t.i.d for 1 week followed by 2 placebo tablets p.o. t.i.d. for 11 weeks.
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sugar pill that looks like sildenafil tablets
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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 |
---|---|---|
6 Minute Walk Distance
時間枠:Weeks 1, 13
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Change in distance walked between week 1 and week 13 were compared.
The difference between the two time points is reported.
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Weeks 1, 13
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Cardiopulmonary Exercise Test Work Rate
時間枠:Weeks 1 and 13
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Work rate (the amount of energy being expended to cycle) was assessed at weeks 1 and 13.
The change in maximum work measured during CPET between weeks 1 and 13 is reported.
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Weeks 1 and 13
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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 |
---|---|---|
Cystic Fibrosis Quality of Life-Revised Respiratory Domain Score
時間枠:Assessed at weeks 1 and 13
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The CFQ-R Respiratory domain score (scale 0-100 with higher scores indicating better quality of life) was assessed at weeks 1 and 13.
The change in the score between week 1 and week 13 is reported.
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Assessed at weeks 1 and 13
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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
捜査官
- 主任研究者:Jennifer L Taylor-Cousar, MD、National Jewish Health
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
- Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G; Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005 Nov 17;353(20):2148-57. doi: 10.1056/NEJMoa050010. Erratum In: N Engl J Med. 2006 Jun 1;354(22):2400-1.
- Orenstein DM, Higgins LW. Update on the role of exercise in cystic fibrosis. Curr Opin Pulm Med. 2005 Nov;11(6):519-23. doi: 10.1097/01.mcp.0000181476.92810.07.
- Pianosi P, Leblanc J, Almudevar A. Peak oxygen uptake and mortality in children with cystic fibrosis. Thorax. 2005 Jan;60(1):50-4. doi: 10.1136/thx.2003.008102.
- Almajed A, Lands LC. The evolution of exercise capacity and its limiting factors in cystic fibrosis. Paediatr Respir Rev. 2012 Dec;13(4):195-9. doi: 10.1016/j.prrv.2012.01.001. Epub 2012 Feb 10.
- Jiang K, Jiao S, Vitko M, Darrah R, Flask CA, Hodges CA, Yu X. The impact of Cystic Fibrosis Transmembrane Regulator Disruption on cardiac function and stress response. J Cyst Fibros. 2016 Jan;15(1):34-42. doi: 10.1016/j.jcf.2015.06.003. Epub 2015 Jun 25.
- Mourani PM, Sontag MK, Ivy DD, Abman SH. Effects of long-term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease. J Pediatr. 2009 Mar;154(3):379-84, 384.e1-2. doi: 10.1016/j.jpeds.2008.09.021. Epub 2008 Oct 31.
- Montgomery GS, Sagel SD, Taylor AL, Abman SH. Effects of sildenafil on pulmonary hypertension and exercise tolerance in severe cystic fibrosis-related lung disease. Pediatr Pulmonol. 2006 Apr;41(4):383-5. doi: 10.1002/ppul.20393.
- Lubamba B, Lecourt H, Lebacq J, Lebecque P, De Jonge H, Wallemacq P, Leal T. Preclinical evidence that sildenafil and vardenafil activate chloride transport in cystic fibrosis. Am J Respir Crit Care Med. 2008 Mar 1;177(5):506-15. doi: 10.1164/rccm.200703-344OC. Epub 2007 Nov 15.
- Taylor-Cousar JL, Wiley C, Felton LA, St Clair C, Jones M, Curran-Everett D, Poch K, Nichols DP, Solomon GM, Saavedra MT, Accurso FJ, Nick JA. Pharmacokinetics and tolerability of oral sildenafil in adults with cystic fibrosis lung disease. J Cyst Fibros. 2015 Mar;14(2):228-36. doi: 10.1016/j.jcf.2014.10.006. Epub 2014 Nov 13.
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
2015年12月1日
一次修了 (実際)
2018年1月18日
研究の完了 (実際)
2018年1月29日
試験登録日
最初に提出
2015年12月3日
QC基準を満たした最初の提出物
2015年12月7日
最初の投稿 (見積もり)
2015年12月10日
学習記録の更新
投稿された最後の更新 (実際)
2019年7月24日
QC基準を満たした最後の更新が送信されました
2019年7月12日
最終確認日
2019年7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
- NationalJewishHealth
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