A Phase II, Multicentre, Randomised, Double-blind, Placebo Controlled Clinical Trial to Investigate the Efficacy and Safety of Aerosolised Liposomal Ciclosporin A Versus Aerosolised Placebo in the Prevention of Bronchiolitis Obliterans Syndrome in Lung Transplant Patients
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- The primary objective is to compare cumulative BOS-free survival of patients recieving L-CsA or placebo.
研究概览
简要总结
Immunosuppression is a key intervention in patients with solid organ transplant and is usually achieved by combination therapy with systemic CsA or tacrolimus with azathioprine, mycophenolate mofetil (MMF), or corticoids. However, the outcomes after lung transplantation are poor when compared with those after heart, kidney, or liver transplantation, with a survival rate of only 55% for recipients of lung transplants.
Additional application of aerosolised L-CsA should suppress T-cell activation in the lung tissue and subsequently BOS development. The overall purpose of this phase-II/III study is to obtain efficacy and safety data of L-CsA in the prevention of BOS.
详细描述
Preventive therapeutic intervention by L-CsA is primarily aimed to suppress T-lymphocyte suppression and inflammatory responses and secondly to prevent fibrotic effects making it more likely to be effective in early stages of BOS. Early development of BOS, which mostly will not be diagnosed, and acute organ rejections are strongly patho-physiological associated. Prevention of the very early development of chronic rejection by L-CsA post LTX may be the ideal starting point for IMP application.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient's written informed consent
- •Received a single lung, bilateral lung or heart/lung transplantation between 6 weeks and 26 weeks prior to first IMP administration.
- •Male or female, 18 years of age
- •Capable of self-administration of medications
- •Capable of understanding the purpose and risk of the clinical trial
- •Received the following immunosuppressive agents and dosages for maintenance therapy:
- •Tacrolimus and
- •Mycophenolate mofetil (MMF) 1 to 3 g/day and
- •Prednisone or any other steroid therapy; tapered down
- •Female patients with childbearing potential must have a negative urine pregnancy test prior to first IMP administration.
- •Estimated life expectancy > 6 month
排除标准
- •Any previous episode of bronchiolitis obliterans (BO) or bronchiolitis obliterans syndrome (BOS) of grade 1 or higher
- •Any active invasive bacterial, viral or fungal infection
- •Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria
- •Received any systemic or topical ciclosporin A within
- •Received any systemic or topical Rosuvastatin
- •Current mechanical ventilation
- •Received a lung re-transplantation
- •Pregnant or breast feeding woman
- •Has known hypersensitivity to ciclosporin A
- •Has a serum creatinine value of more than 265 µmol/L (3 mg/dL)
- •Unlikely to comply with visits, inhalation procedures or spirometric measurements
- •Receipt of an investigational drug within 4 weeks prior to first administration of IMP
- •Any co-existing medical condition that in the investigator's judgement
- •Psychiatric disorders or altered mental status
- •Patient was previously enrolled in the present clinical trial
研究组 & 干预措施
L-CsA
Twice daily inhalation of 2.5 ml/10 mg L-CsA for 96 weeks
干预措施: Cyclosporine Inhalation Solution (Drug)
L-CsA placebo
Twice daily inhalation of 2.5 ml aerosolised placebo (carrier) for 96 weeks (24 months)
干预措施: Cyclosporine Inhalation Solution (Drug)
结局指标
主要结局
The primary objective is to compare cumulative BOS-free survival of patients recieving L-CsA or placebo.
时间窗: 2 years
BOS stage 1 and higher is considered as BOS for the primary endpoint.
次要结局
- Cumulative mean incidence of BOS 12, 18 and 24 months after first IMP administration(2 years)