Effect of add-on Doxofylline on Lung Function in Stable COPD

NCT ID: NCT04238221

Last Updated: 2020-03-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2020-11-30

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:

1. plethysmography

2. DLCO

3. maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP)

4. 6-minute walk test (6MWT) with the assessment of dyspnea scale (Borg scale) at rest and after exercise.

Sixty minutes after the administration of the usual chronic inhalation therapy, patients will then perform the same respiratory lung functional bundle of tests as detailed above (from 1 to 3).

Subsequently, patients will be randomized in two parallel arms (arm A and arm B). Patients assigned to arm A will be prescribed 30-day treatment with doxofylline 400 mg bid, in addition to their chronic inhalation therapy, and will take the first dose of the medication; patients assigned to arm B will have their chronic therapy unchanged.

Randomization, drug administration and patient training will be performed by an operator not involved in patients' recruitment, data collection and analysis.

180 minutes after the administration of the usual chronic inhalation therapy, patients will repeat the lung function bundle from point 1 to 3.

During the subsequent 4-week treatment, patients' compliance will be monitored by telephone calls. Any adverse event will be registered and will be treated according to our center's standard operating procedures and good clinical practice by the treating physician.

After 4 weeks, before the administration of the morning dose, patients will be asked to complete the CAT, mMRC and SGRQ questionnaires and to perform the baseline functional bundle detailed in points 1 to 4. Patients will be asked to take the home inhalation therapy, as well as doxofylline if arm A. Respiratory function tests from points 1 to 3 will be repeated 60 minutes after drug administration. After that, patients assigned to Arm B will take the first dose of doxofylline. Respiratory function tests from points 1 to 3 will then be repeated 180 minutes after inhalation therapy administration. Eventually, the 6-MWT will be performed by patients assigned to Arm A, with assessment of the Borg dyspnea scale.

During the subsequent 4 weeks, patients assigned to arm B will be prescribed therapy with doxofylline 400 mg bid in addition to their chronic inhalatory therapy, while patients assigned to arm A will have only their usual chronic inhalation therapy. Compliance monitoring and adverse event management will be handled as previously discussed.

At the end of the 4 weeks, before the administration of the morning dose, patients will be asked to complete the CAT, mMRC and SGRQ questionnaires and to perform the baseline functional bundle detailed in points 1 to 4. Patients will be asked to take the home inhalation therapy, as well as doxofylline if arm B. Respiratory function tests from points 1 to 3 will be repeated 60 minutes and 180 minutes after drug administration. Eventually, the 6-MWT will be performed by patients assigned to Arm B, with assessment of the Borg dyspnea scale.

A 30-day follow up will be performed after the last visit, in order to register any late drug adverse reaction or adverse events..

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Doxofylline

Intervention Type: DRUG

Patients will receive a 4-week treatment with doxofylline 400 mg bid, in addition to their chronic usual inhalation therapy.

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

Group Type: EXPERIMENTAL

Doxofylline

Intervention Type: DRUG

Patients will receive a 4-week treatment with doxofylline 400 mg bid, in addition to their chronic usual inhalation therapy.

Interventions

Doxofylline

Patients will receive a 4-week treatment with doxofylline 400 mg bid, in addition to their chronic usual inhalation therapy.

Intervention Type: DRUG

Other Intervention Names

Ansimar

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Milan

OTHER

Sponsor Role: lead

Responsible Party

Pierachille Santus, MD, PhD

Professor of Respiratory Diseases, Head of the Respiratory Disease Unit, L. Sacco University Hospital, Milan, Italy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

L. Sacco Hospital

Milan, , Italy

Countries

Italy

Central Contacts

Pierachille Santus, MD, PhD

Role: CONTACT

pierachille.santus@unimi.it

0239043801

Dejan Radovanovic, MD

Role: CONTACT

dejan.radovanovic@unimi.it

Facility Contacts

Pierachille Santus, MD, PhD

Role: primary

pierachille.santus@unimi.it

0239042801

Other Identifiers

01-PNSNP-2020

Identifier Type: -

Identifier Source: org_study_id