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Atorvastatin Effect on Reduction of COPD Exacerbations (Captain)

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ClinicalTrials.gov Identifier: NCT04789057
Recruitment Status : Not yet recruiting
First Posted : March 9, 2021
Last Update Posted : September 23, 2021
Sponsor:
Collaborator:
Medical Research Agency
Information provided by (Responsible Party):
Medical University of Bialystok

Study Description
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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.

Condition or disease Intervention/treatment Phase
Copd COPD Exacerbation Smoking Gene Expression Atorvastatin Drug: Atorvastatin 40 Mg Oral Tablet Drug: Placebo Phase 4

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 460 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Non-commercial Clinical Trial of Statins CAncer Preventive and Pleiotropic TherApy IN Smokers With Chronic Obstructive Pulmonary Disease (COPD)
Estimated Study Start Date : November 1, 2021
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Statins
Atorvastatin 40 mg treatment, p.o., QD
 Drug: Atorvastatin 40 Mg Oral Tablet
p.o., once daily
Other Name: Atorvastatin
Placebo Comparator: Placebo
Placebo tablet, p.o., QD
 Drug: Placebo
p.o., once daily
Other Name: Placebo control group


Outcome Measures
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Primary Outcome Measures :
  1. COPD exacerbation rate [ Time Frame: 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.

  2. Time to the COPD exacerbation [ Time Frame: 56 weeks ]
    The time to the first exacerbation will be compared between the Intervention and Placebo groups.


Secondary Outcome Measures :
  1. Changes in forced expiratory volume in the first second (FEV1) [ Time Frame: 56 weeks ]
    The differences in absolute value between Placebo and Atorvastatin group will be evaluated in time points [Visit 1 ,Visit 3,Visit 4, Visit 5, Visit 6 and Visit 8], and the relative change between Visit 1 and following time points [Visit 3 - Visit 8] in both arms will be compared.

  2. Changes in health-related quality of life [ Time Frame: 56 weeks ]
    The St George's Respiratory Questionnaire (SGRQ) score will be used and the differences in absolute value between Placebo and Atorvastatin group will be evaluated in time points [Visit 2 , Visit 5, and Visit 7], as well as the - relative change between Visit 2 and following time points [Visit 5 and Visit 7] in both arms will be compared. Scores range from 0 to 100; higher scores indicating more limitations.

  3. Changes of inflammatory pathway gene expression [ Time Frame: 56 weeks ]
    The gene expression will be evaluated in the peripheral blood leucocytes (PBL) by RNA-seq analysis, at visit Visit 1, Visit 2, Visit 5 and Visit 7, and the differences between Placebo and Atorvastatin groups will be analyzed, as well as a relative change between visits Visit 1 and Visit 2, Visit 5 and Visit 7 in both arms will be compared.

  4. Changes in peripheral blood leucocyte count [ Time Frame: 56 weeks ]
    The peripheral blood leucocytes count will be measured and the differences in absolute values between Placebo and Atorvastatin group will be calculated in time points Visit 1 ,Visit 3, Visit 5 and Visit 7, as well as a relative change between visits Visit 1 and Visit 2, Visit 3, Visit 5 , Visit 7 in both arms will be compared.

  5. Changes in the blood fibrinogen concentrations [ Time Frame: 56 weeks ]
    A blood fibrinogen concentration will be measured and the differences in absolute values between Placebo and Atorvastatin group will be calculated in time points Visit 1 ,Visit 3, Visit 5 and Visit 7, as well as a relative change between visits Visit 1 and Visit 2, Visit 3, Visit 5 , Visit 7 in both arms will be compared.

  6. Changes in the blood Interleukin-6 concentrations [ Time Frame: 56 weeks ]
    The Interleukin-6 blood concentrations will be measured and the differences in absolute values between Placebo and Atorvastatin group will be calculated in time points Visit 1 ,Visit 3, Visit 5 and Visit 7, as well as a relative change between visits Visit 1 and Visit 2, Visit 3, Visit 5 , Visit 7 in both arms will be compared.

  7. Changes in the blood high sensitivity C - reactive protein concentrations [ Time Frame: 56 weeks ]
    The blood high sensitivity C - reactive protein concentrations will be measured and the differences in absolute values between Placebo and Atorvastatin group will be calculated in time points Visit 1 ,Visit 3, Visit 5 and Visit 7, as well as a relative change between visits Visit 1 and Visit 2, Visit 3, Visit 5 , Visit 7 in both arms will be compared.


Other Outcome Measures:
  1. Change from baseline in pre-dose values of plethysmography [ Time Frame: 56 weeks ]
    The functional residual volume (FRC) will be evaluated at Visit 2, Visit 5 and Visit 7, and changes from Visit 1 will be calculated, as well as compared between studied groups.

  2. Change in Inspiratory capacity (IC) [ Time Frame: 56 weeks ]
    The Inspiratory capacity (IC) will be evaluated will be evaluated at Visit 2, Visit 5 and Visit 7, and changes from Visit 1 will be calculated, as well as compared between studied groups.

  3. Change in 6 minute walking distance (6MWD) test result [ Time Frame: 56 weeks ]
    The 6MWD tests will be performed at Visit 2, Visit 5 and Visit 7, and changes from Visit 1 will be calculated, as well as compared between studied groups.

  4. The rate of hospitalizations (pulmonary or MACE) [ Time Frame: 56 weeks ]
    The number of hospitalizations during the treatment and follow-up phases will be evaluated, and compared between studied groups.

  5. Changes in blood pressure [ Time Frame: 56 weeks ]
    The changes in blood pressure from Visit 1 will be evaluated at Visit 2, Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7, and changes from Visit 1 will be calculated, as well as compared between studied groups.

  6. Changes in heart rate (HR) [ Time Frame: 56 weeks ]
    The changes in HR from Visit 1 will be evaluated at Visit 2, Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7, and changes from Visit 1 will be calculated, as well as compared between studied groups.

  7. Changes in hematology results [ Time Frame: 56 weeks ]
    The changes in hematology results from visit Visit 1 will be evaluated, at Visit 3, Visit 5, and Visit 7, as well as the differences between studied groups will be compared.

  8. Changes in biochemistry results [ Time Frame: 56 weeks ]
    The changes in biochemistry results from visit Visit 1 will be evaluated, at Visit 3, Visit 5, and Visit 7, as well as the differences between studied groups will be compared.

  9. Changes in lipids profile [ Time Frame: 56 weeks ]
    The changes in lipids profile results from visit Visit 1 will be evaluated, at Visit 3, Visit 5, and Visit 7, as well as the differences between studied groups will be compared.

  10. Changes in blood glucose levels [ Time Frame: 56 weeks ]
    The changes in blood glucose concentrations from Visit 1 will be evaluated at Visit 7, and compared between studied groups.

  11. Changes in HbA1c levels [ Time Frame: 56 weeks ]
    The changes in HbA1c levels from Visit 1 will be evaluated at Visit 7, and compared between studied groups.

  12. Changes in the blood AspAT and ALAT concentrations [ Time Frame: 56 weeks ]
    The changes in blood AspAT and ALAT concentrations from Visit 1 will be evaluated, at Visit 2, Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7, and compared between studied groups.

  13. Changes in the blood CPK concentrations [ Time Frame: 56 weeks ]
    The changes in blood CPK concentrations from Visit 1 will be evaluated, at Visit 2, Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7, and compared between studied groups.

  14. Change in a transfer factor of the lung for carbon monoxide (DLCO) [ Time Frame: 56 weeks ]
    The DLCO will be evaluated at Visit 2, Visit 5 and Visit 7, and the changes from Visit 1 will be calculated, as well as compared between studied groups.


Eligibility Criteria
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Ages Eligible for Study:   40 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04789057


Contacts
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Contact: Robert Mróz, Prof. MD +48 85 74095 22 robert.mroz@umb.edu.pl

Locations
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Poland
Medical University Hospital
Bialystok, Poland, 15-540
Contact: Robert Mróz, Prof. MD    +48 85 740 95 22    robert.mroz@umb.edu.pl   
Principal Investigator: Robert Mróz, Professor         
Sponsors and Collaborators
Medical University of Bialystok
Medical Research Agency
Investigators
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Principal Investigator: Robert Mróz, Prof. MD Medical University of Bialystok
More Information
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Responsible Party: Medical University of Bialystok
ClinicalTrials.gov Identifier: NCT04789057    
Other Study ID Numbers: 2019/ABM/01/00074
2019/ABM/01/00074 ( Other Identifier: Medical Research Agency )
First Posted: March 9, 2021    Key Record Dates
Last Update Posted: September 23, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: According to the agreement with the funding institution (Medical Research Agency), the sponsor and research centers must obtain the consent of the funding institution to disclose the clinical trial data.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Atorvastatin
Anticholesteremic Agents
 Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors