Effect of Doxofylline on Bronchial Obstruction, in add-on to Maximal Inhalation Therapy, in Clinically Stable COPD Patients.
Trial Snapshot
- Phase
- Phase 4
- Sponsor
- University of Milan
- Enrollment
- 78
- Locations
- 1
- Primary Endpoint
- Difference in changes in FEV1 after 4 weeks of treatment
Study Overview
Brief Summary
It is a phase IV, prospective, interventional, single blind, randomized, crossover trial in which the investigators will evaluate the effects of a 4-week treatment with doxofylline 400 mg bid, in add-on to maximal inhalation therapy, in clinically stable COPD patients.
Detailed Description
The investigators will evaluate the effects of a 4-week treatment with doxofylline 400 mg, in add-on to maximal inhalation therapy (bronchodilators with or without a fixed dose combination with inhaled corticosteroids), in clinically stable COPD patients.
After screening and collection of informed consent, study participants will undergo a 7-day run-in, during which compliance to inhaled therapy and clinical stability will be assessed.
On the first visit patients will complete questionnaires (CAT, mMRC and SGRQ) to assess baseline respiratory function and health related quality of life.
After the first visit, patients will undergo a washout period during which the inhaled therapy will be withheld for 24 hours (7 days in case of chronic therapy with tiotropium).
The following day (the 8th day in case of tiotropium use), patients will perform the baseline measurement of the following:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Care Provider, Investigator, Outcomes Assessor)
Masking Description
Randomization, drug administration and patient training will be performed by an operator not involved in patients' recruitment and in the data collection and analysis.
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •COPD diagnosis for at least 6 months, according to current European Respiratory Society guidelines
- •baseline FEV1 ≤ 80% of predicted value
- •active or former smokers with smoking history ≥ 10 pack-years
- •patients chronically treated with a long acting muscarinic antagonist (LAMA) and a long acting beta-2 agonists (LABA), in association with or without an inhaled corticosteroid (ICS)
- •clinically stable disease for 6 months.
Exclusion Criteria
- •previous or current diagnosis of bronchial asthma
- •previous lung volume reduction through surgery or endobronchial valves
- •inability to perform respiratory function tests according to international standards, or contraindications to perform 6-minute walking test
- •known allergy or intolerance to doxofylline
- •current or potential pregnancy
- •mini-Mental test <21
- •congestive heart failure NYHA III or IV
- •recent (<6 months) myocardial infarction
- •unstable arrhythmias
- •chronic hypotension
- •active peptic ulcer
- •severe liver disease
- •active neoplasia
- •history of drug or alcohol abuse.
Arms & Interventions
Doxofylline+inhalation therapy
4-week treatment with doxofylline tablets 400 mg bid in addition to maximal inhalation therapy, followed by 4-week treatment of maximal inhalation therapy only
Intervention: Doxofylline (Drug)
Inhalation therapy
4-week treatment with maximal inhalation therapy only, followed by 4-week treatment with doxofylline tablets 400 mg bid in addition to maximal inhalation therapy
Intervention: Doxofylline (Drug)
Outcomes
Primary Outcomes
Difference in changes in FEV1 after 4 weeks of treatment
Time Frame: 4-8 weeks
Difference between changes in the Forced Expiratory Volume in one second (FEV1) measured at baseline and the FEV1 after 4 weeks of treatment with doxofylline in addition to inhalation therapy, measured 30 minutes before the morning dose of doxofylline plus inhalation therapy, and changes in the FEV1 measured at baseline and the FEV1 after 4 weeks of treatment with inhalation therapy only, measured 30 minutes before the morning dose of inhalation therapy.
Secondary Outcomes
- Changes in distance covered in 6-minute walking test 180' after drug administration(4-8 weeks)
- Difference in changes in resting and effort dyspnea after 4 weeks of treatment(4-8 weeks)
- Difference in changes in vital capacity after 4 weeks of treatment(4-8 weeks)
- Difference in changes in residual volume after 4 weeks of treatment(4-8 weeks)
- Change in FEV1 60' after drug administration(60 minutes)
- Difference in changes in distance covered in 6-minute walking test after 4 weeks of treatment(4-8 weeks)
- Changes in resting and effort dyspnea 180' after drug administration(4-8 weeks)
- Difference in changes in modified Medical Research Council (mMRC) scale after 4 weeks of treatment(4-8 weeks)
- Difference in changes in COPD Assessment Test (CAT) score after 4 weeks of treatment(4-8 weeks)
- Difference in changes in St. George Respiratory Questionnaire (SGRQ) after 4 weeks of treatment(4-8 weeks)
- Difference in changes in functional residual capacity after 4 weeks of treatment(4-8 weeks)
- Difference in changes in inspiratory capacity after 4 weeks of treatment(4-8 weeks)
- Difference in changes in specific airway resistance after 4 weeks of treatment(4-8 weeks)
Investigators
Pierachille Santus, MD, PhD
Professor of Respiratory Diseases, Head of the Respiratory Disease Unit, L. Sacco University Hospital, Milan, Italy
University of Milan