Clinical trial NCT04789057: Atorvastatin Effect on Reduction of COPD Exacerbations
Official title: Non-commercial Clinical Trial of Statins CAncer Preventive and Pleiotropic TherApy IN Smokers With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Copd
COPD Exacerbation
Smoking
Gene Expression
Atorvastatin
Lead sponsor: Medical University of Bialystok
Sponsor class: OTHER
Collaborators: name: Medical Research Agency, Poland
First posted: 2021-03-09
Enrollment: 460
Sex: ALL
Minimum age (years): 40
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Subject \[male or female\] is aged 40 years and older.
3. Subject is able to understand and comply with the protocol requirements and instructions and is likely to complete the study as planned.
4. 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.
5. At least two moderate/severe COPD exacerbations, or at least one leading to hospitalization or ICU admission within 12 months, preceding screening visit.
6. Current or ex-smokers who have a smoking history of at least 10 pack years.

Exclusion Criteria:

1. Contraindication to statin therapy included but not limited to: known poliomyelitis, motor neuron disease, cranial or temporal arteritis, stroke or myopathy.
2. Statin use within the last 3 months prior to study start.
3. Prior diagnosis of statin induced myopathy or hypersensitivity reaction to another HMG-CoA-reductase inhibitor.
4. Using e-cigarettes or I IQOS tobacco heating system.
5. Pregnant or nursing (lactating) women.
6. Women of child bearing potential, unless they are using effective method of contraception during dosing of study treatment.
7. Patient with a clinically significant abnormality at visit 1 in investigator opinion.
8. Patients with a clinically relevant laboratory abnormality at visit 1 in investigator opinion.
9. Patients with a history of malignancy of any organ system (including lung cancer).
10. Patients unable to perform acceptable spirometry and lung volumes procedures.
11. 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 1.
12. Patients who have had a respiratory tract infection within 4 weeks prior to visit1.
13. Patients requiring oxygen therapy (\>15hr/day) on a daily basis for chronic hypoxemia.
14. Patients with a history of asthma or onset of symptoms prior to age 40 years
15. Patients with concomitant pulmonary disease (e.g. lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, tuberculosis).
16. Patients with primary bronchiectasis.
17. Patients with a diagnosis of α-1 antitrypsin deficiency (AATD).
18. Patients with pulmonary lobectomy or lung volume reduction surgery or lung transplantation.
19. Active abuse of drugs or alcohol, poor compliance anticipated.
20. 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.
21. Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study.
22. Use of other investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening visit.
23. Those unable in the opinion of the Investigator to comply fully with the study requirements.

Primary outcomes:
measure: COPD exacerbation rate
timeFrame: 56 weeks
measure: Time to the COPD exacerbation
timeFrame: 56 weeks
Secondary outcomes:
measure: Changes in forced expiratory volume in the first second (FEV1)
timeFrame: 56 weeks
measure: Changes in health-related quality of life
timeFrame: 56 weeks
measure: Changes of inflammatory pathway gene expression
timeFrame: 56 weeks
measure: Changes in peripheral blood leucocyte count
timeFrame: 56 weeks
measure: Changes in the blood fibrinogen concentrations
timeFrame: 56 weeks
measure: Changes in the blood Interleukin-6 concentrations
timeFrame: 56 weeks
measure: Changes in the blood high sensitivity C - reactive protein concentrations
timeFrame: 56 weeks
Other outcomes:
measure: Change from baseline in pre-dose values of plethysmography
timeFrame: 56 weeks
measure: Change in Inspiratory capacity (IC)
timeFrame: 56 weeks
measure: Change in 6 minute walking distance (6MWD) test result
timeFrame: 56 weeks
measure: The rate of hospitalizations (pulmonary or MACE)
timeFrame: 56 weeks
measure: Changes in blood pressure
timeFrame: 56 weeks
measure: Changes in heart rate (HR)
timeFrame: 56 weeks
measure: Changes in hematology results
timeFrame: 56 weeks
measure: Changes in biochemistry results
timeFrame: 56 weeks
measure: Changes in lipids profile
timeFrame: 56 weeks
measure: Changes in blood glucose levels
timeFrame: 56 weeks
measure: Changes in HbA1c levels
timeFrame: 56 weeks
measure: Changes in the blood AspAT and ALAT concentrations
timeFrame: 56 weeks
measure: Changes in the blood CPK concentrations
timeFrame: 56 weeks
measure: Change in a transfer factor of the lung for carbon monoxide (DLCO)
timeFrame: 56 weeks
Locations:
city: Bialystok
country: Poland
facility: Medical University Hospital
Study officials:
affiliation: Medical University of Bialystok
name: Robert Mróz, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: