The Effect of the ET-1 Receptor Antagonist, Bosentan on Patients With Poorly Controlled Asthma-A 17 Week, Double-blind, Placebo Controlled Crossover Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Change in FEV1
研究概览
简要总结
Hypothesis: The endothelin-1 receptor antagonist, bosentan when added to the treatment of asthma patients who are symptomatic despite the use of controller therapy will improve asthma symptoms and physiology.
Twenty patients with a diagnosis of asthma, between the ages of 21 and 70 who are symptomatic despite the use of at least one controller medication will be randomized to either placebo or active medication for an 8 week period (initial 4 weeks is at 1/2 of final dose as per package insert and FDA approval). Measures of lung function and symptoms will be recorded. Patients will then cross over, so that patients initially on placebo will receive active drug for 8 weeks and those initially on active drug will receive placebo. The same endpoints will be measured. The acute bronchodilator effects of the drug will also be tested on the first day of therapy at the full therapeutic dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of asthma, maintained on a minimum of 1 anti-inflammatory/controller and daily long acting B-agonist therapy with inadequate control of symptoms. (Defined as symptoms including wheezing, chest tightness or shortness of breath occurring at least 3 times a week or requiring use of "rescue" short-acting B-agonist at least 3 times a week).
- •FEV1 less than 80% of predicted and greater than 40% at screening visit.
- •A minimum of 12% reversibility of FEV1 after albuterol on screening visit or previously documented during the prior two years.
- •Women of childbearing potential must use 2 non-hormonal methods of birth control (2 methods between the subject and her partner) while on the study and for 1 month after the last dose of study medication.
- •Male subjects must use two non hormonal methods of birth control (2 methods between the subject and his partner) while on the study and for 1 month after the last dose of study medication.
排除标准
- •History of liver disease, clinically significant cardiac disease, renal disease or pulmonary disease other than asthma. Patients with clinically significant laboratory abnormalities of LFTs/bilirubin (AST/ALT, TBili, alkaline phosphatase) and clinically significant anemia will be excluded. Clinically significant anemia will be defined as any anemia resulting in serum Hgb more than 1 gm/dl below the LLN, Patients with isolated minimal elevations of bilirubin (eg. as occurs in Gilbert's disease) or minimal elevations in transaminases (less than 1.2 x ULN) without a history of liver disease, risk factors for liver disease or symptoms of liver disease may still be included in the study at the investigator's discretion, but will have LFT testing at each study visit.)
- •Cigarette history of >10 pack years.
- •Predicted inability to adhere to medication regimen or documentation requirements of the study (symptom and medication diaries).
- •Respiratory infection during 30 days preceding screening visit.
- •Requirement for change in scheduled asthma medication use, including oral steroid dose change, or acute medical care for asthma during the 30 days preceding screening visit.
- •Predicted inability to safely refrain from B-agonist use for the required amount of time on study visit days.
- •Use of tiotropium
- •Pregnancy, breast feeding or the use of hormonal methods of birth control as the only means of birth control during the study.
- •Use of potent CYP3A4 and CYP2C9 inhibitors, including, but not limited to azole antifungals, amiodarone, glyburide, warfarin, cyclosporine, ritonavir, other medications potentially toxic to the liver or bone marrow.
- •Use of any illegal drugs or alcohol abuse.
研究组 & 干预措施
1 Crossover
干预措施: bosentan (Drug)
1 Crossover
干预措施: placebo (Drug)
结局指标
主要结局
Change in FEV1
时间窗: 1, 2, 4 hours after dosing
Peak Flow
时间窗: last 7 days of each dosing period
Symptom Scores
时间窗: Last 7 days of each dosing period
Symptom score could range from a minimum of 7 (no symptoms) to 35 (severe symptoms)
次要结局
- FEV1(end of dosing period)
- Rescue Beta-agonist(end of each dosing period)
- Asthma Control Test Questionnaire(end of each dosing period)
研究者
Mark Metersky
MD
UConn Health