Evaluation of Atorvastatin on COPD Exacerbation Reduction in Smokers: A Randomized, Placebo-Controlled Clinical Trial
- Trial ID
- 2024-516714-37-00
- Protocol
- 2019/ABM/01/00074
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **effectiveness** of atorvastatin compared to a matched placebo control in reducing exacerbations in patients with **chronic obstructive pulmonary disease (COPD)**. This is clinically relevant as reducing exacerbations can significantly improve patient outcomes and decrease healthcare utilization in COPD management.
Secondary objectives include:
- Comparing the effectiveness of atorvastatin with a placebo on lung function and health-related quality of life changes in COPD patients.
- Providing evidence that atorvastatin exerts direct anti-inflammatory activity regulated at the gene level, aiming to develop atorvastatin response biomarkers for personalized treatment of COPD.
Participants
The clinical trial focuses on individuals diagnosed with **chronic obstructive pulmonary disease (COPD)**, aiming to assess the effectiveness of atorvastatin in reducing COPD exacerbations. The study population includes both male and female participants aged 40 years and older, encompassing those with stable COPD characterized by persistent airflow limitation, as defined by the GOLD guidelines. Participants are required to have experienced at least two moderate or severe COPD exacerbations, or at least one that led to hospitalization or ICU admission within the 12 months preceding the screening visit. The trial includes current or ex-smokers with a smoking history of at least 10 pack years, excluding those who only use e-cigarettes or IQOS tobacco heating systems. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on their ability to understand and comply with the study protocol, ensuring they are likely to complete the study as planned. The study includes a vulnerable population, highlighting the importance of careful monitoring and ethical considerations throughout the trial.
Plans and Procedures
The clinical trial is designed to evaluate the effectiveness of **atorvastatin** in reducing exacerbations in patients with **chronic obstructive pulmonary disease (COPD)**. This is a Phase III, randomized, double-blind, placebo-controlled study. Participants will be randomly assigned to receive either atorvastatin, 40 mg, in the form of film-coated tablets, or a matched placebo. The trial is expected to last until December 31, 2025, with participant involvement spanning a maximum treatment period of 52 weeks.
The study will commence with an inclusion (screening) visit, where eligibility criteria will be assessed. Key inclusion criteria include patients aged 40 years and older with stable COPD, a history of smoking of at least 10 pack years, and a record of at least two moderate or severe COPD exacerbations in the past year. Following the screening, eligible participants will be enrolled and randomized into the study. Subsequent follow-up visits will be scheduled at regular intervals to monitor the primary endpoints, which include the exacerbation rate and time to exacerbation, as well as secondary endpoints such as changes in forced expiratory volume, health-related quality of life, and inflammatory markers.
The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The trial aims to provide comprehensive data on the potential benefits of atorvastatin in managing COPD exacerbations, contributing valuable insights into the treatment of this chronic condition.
Treatment
The clinical trial involves the administration of **Atorvastatin**, marketed under the name Atoris, as the experimental medication. Atoris is provided in the form of **film-coated tablets**, each containing 40 mg of the active substance **atorvastatin**. The tablets are intended for **oral use**. Participants in the trial will receive a maximum daily dose of 40 mg, with the total dose not exceeding 14,560 mg over the course of the study. The treatment period is set for a maximum of 52 weeks. The pharmaceutical product is manufactured by KRKA, D.D., Novo Mesto, and is authorized for use in Poland. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.
The study also includes a **placebo** as a non-experimental treatment to serve as a control. The placebo is designed to match the experimental medication in appearance and administration route, ensuring blinding of the study. The placebo will be administered orally, following the same dosing schedule as the active treatment, to maintain consistency across the study groups. The use of a placebo allows for a direct comparison of the effects of atorvastatin on the reduction of exacerbations in patients with chronic obstructive pulmonary disease (COPD).
Efficacy
The efficacy of atorvastatin in reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD) will be assessed through a non-commercial clinical trial. The primary endpoints for evaluating efficacy include the **exacerbation rate** and the **time to exacerbation**. Secondary endpoints encompass a range of parameters such as the duration of exacerbation, changes in forced expiratory volume in the first second (FEV1), and changes in health-related quality of life as measured by the St. George's Respiratory Questionnaire (SGRQ) score. Additionally, changes in inflammatory pathway gene expression in peripheral blood mononuclear cells (PBMCs) will be analyzed using whole transcriptome RNA-seq analysis. Other secondary endpoints include changes in blood inflammatory markers, plethysmography measurements, 6-minute walking distance (6MWD), hospitalization rates, and changes in vital signs and laboratory findings.
Data collection will occur at specified timepoints throughout the trial, with assessments conducted using validated scales and laboratory tests. The trial is designed to compare the effects of atorvastatin with a matched placebo control, ensuring a rigorous evaluation of its efficacy in the target population. The study will follow a structured schedule for measuring and analyzing these parameters to provide comprehensive insights into the therapeutic potential of atorvastatin in COPD management.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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 or severe COPD exacerbations, or at least one leading to hospitalization or ICU admission within 12 months, proceeding screening visit.
- Current or ex-smokers who have a smoking history of at least 10 pack years [only use of e-cigarettes or IQOS tobacco heating system cannot be use as a equivalent of classic cigarettes smoking].
Exclusion Criteria
- 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.
- CPK levels significantly elevated (> 5 times ULN).
- Using e-cigarettes or IQOS tobacco heating system.
- Pregnant or nursing (lactating) women.
- Women of childbearing 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.
- Subject has known active malignancy of any organ system, i.e., clinical evidence of current malignancy or not in stable remission for at least 5 years since completion of last treatment with exception of non-invasive basal cell carcinoma, squamous cell carcinoma of the skin or cervical intraepithelial neoplasia.
- 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 1.
- Patients who have had a respiratory tract infection within 4 weeks prior to visit 1.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Poland | Not Recruiting | 15 Dec 2020 | 480 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo | Placebo | N/A | — | — | — | N/A |
Atoris, 40 mg, tabletki powlekane | Test | TABLETKI POWLEKANE | ORAL USE | 40 | 52 | PRD6244317 |