Non-commercial Clinical Trial of Statins CAncer Preventive and Pleiotropic TherApy IN Smokers With Chronic Obstructive Pulmonary Disease (COPD)
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 460
- 试验地点
- 2
- 主要终点
- COPD exacerbation rate
研究概览
简要总结
It is a randomized, multicenter, prospective, double-blind, placebo controlled, interventional clinical trial that will be conducted in Poland, in about 12 Hospital Pulmonary Departments to evaluate the effectiveness of atorvastatin on the reduction of inflammation process in patients with chronic obstructive pulmonary diseases, and possible biomarkers for personalized treatment of COPD.
详细描述
It will be a randomized, double-blind, two arm clinical study to assess effect of atorvastatin 40 mg treatment in patients with stable COPD. The whole study duration will include three phases: pre-study screening and enrollment procedures (4 weeks), clinical assessment at dosing (52 weeks), and post study follow up (4 weeks). During the participation in the study subjects will attend Visit 1 (V1, -4 weeks), visit 2 (V2, day 0), visit 3 (V3, week6), visit 4 (V4, week 12), visit 5 (V5, week 26), visit 6 (V6, week 38), visit 7 (V7, week 52), and follow-up end of study visit (EOS, 56 weeks). The study will begin with a 4-weeks screening phase where patients who fulfill preliminary inclusion/exclusion criteria (prior to entry into study), will be given informed consent and screened. The baseline laboratory tests, clinical and medical evaluation including concomitant medication and drug of abuse will be completed to determine patient continuing eligibility to participate in the study.
Upon confirmation of eligibility, the patients will be randomized into two treatment groups receiving one of two medications tested in the study. Each patient enrolled into the clinical study will have to report to the clinic 7 times in order to complete procedures. Blood will be drawn before and during the statin or placebo treatment from patients according to study protocol. This part of the project aims to develop statin response biomarkers for personalized treatment of COPD, based on RNA-sequencing (RNA-seq) information derived from, leukocytes and blood plasma of COPD patients with characterized clinical Atorvastatin response phenotypes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has signed Informed Consent Form and is able to understand the purpose and procedures required for the study and is willing to participate in the study.
- •Subject [male or female] is aged 40 years and older.
- •Subject is able to understand and comply with the protocol requirements and instructions and is likely to complete the study as planned.
- •Patients with stable COPD with persistent airflow limitation (stable COPD (post-bronchodilator FEV1<80% of the predicted normal and post-bronchodilator FEV1/FVC<0,70 at visit 1.) Stage II- IV) and with moderate to very severe airflow limitation according to GOLD guidelines.
- •At least two moderate/severe COPD exacerbations, or at least one leading to hospitalization or ICU admission within 12 months, preceding screening visit.
- •Current or ex-smokers who have a smoking history of at least 10 pack years.
排除标准
- •Contraindication to statin therapy included but not limited to: known poliomyelitis, motor neuron disease, cranial or temporal arteritis, stroke or myopathy.
- •Statin use within the last 3 months prior to study start.
- •Prior diagnosis of statin induced myopathy or hypersensitivity reaction to another HMG-CoA-reductase inhibitor.
- •Using e-cigarettes or I IQOS tobacco heating system.
- •Pregnant or nursing (lactating) women.
- •Women of child bearing potential, unless they are using effective method of contraception during dosing of study treatment.
- •Patient with a clinically significant abnormality at visit 1 in investigator opinion.
- •Patients with a clinically relevant laboratory abnormality at visit 1 in investigator opinion.
- •Patients with a history of malignancy of any organ system (including lung cancer).
- •Patients unable to perform acceptable spirometry and lung volumes procedures.
- •Patients who had a COPD exacerbations that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to visit
- •Patients who have had a respiratory tract infection within 4 weeks prior to visit
- •Patients requiring oxygen therapy (>15hr/day) on a daily basis for chronic hypoxemia.
- •Patients with a history of asthma or onset of symptoms prior to age 40 years
- •Patients with concomitant pulmonary disease (e.g. lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, tuberculosis).
- •Patients with primary bronchiectasis.
- •Patients with a diagnosis of α-1 antitrypsin deficiency (AATD).
- •Patients with pulmonary lobectomy or lung volume reduction surgery or lung transplantation.
- •Active abuse of drugs or alcohol, poor compliance anticipated.
- •Use concomitant medications that are known to interact with atorvastatin: warfarin and other coumarin (vitamin K antagonists) anticoagulants, cyclosporin, gemfibrozil or other non or selective nonsteroidal anti-inflammatory drugs, proton pump inhibitors (PPIs) used by last 6 months.
- •Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study.
- •Use of other investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening visit.
- •Those unable in the opinion of the Investigator to comply fully with the study requirements.
研究组 & 干预措施
Statins
Atorvastatin 40 mg treatment, p.o., QD
干预措施: Atorvastatin 40 Mg Oral Tablet (Drug)
Placebo
Placebo tablet, p.o., QD
干预措施: Placebo (Drug)
结局指标
主要结局
COPD exacerbation rate
时间窗: 56 weeks
The exacerbation of the disease (defined as an acute worsening of respiratory symptoms that results in additional therapy) will be measured during the study treatment and follow-up phases, and compared between studied groups.
Time to the COPD exacerbation
时间窗: 56 weeks
The time to the first exacerbation will be compared between the Intervention and Placebo groups.
次要结局
- Changes in peripheral blood leucocyte count(56 weeks)
- Changes in forced expiratory volume in the first second (FEV1)(56 weeks)
- Changes of inflammatory pathway gene expression(56 weeks)
- Changes in the blood fibrinogen concentrations(56 weeks)
- Changes in the blood Interleukin-6 concentrations(56 weeks)
- Changes in the blood high sensitivity C - reactive protein concentrations(56 weeks)
- Changes in health-related quality of life(56 weeks)