Low-dose Theophylline as Anti-inflammatory Enhancer in Severe Chronic Obstructive Pulmonary Disease

NCT01599871 | Completed Phase 3

• 1 other identifier: 1559-F-447
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 10

Brief Summary

The main objective of the study is to determine the effects of low-dose oral theophylline added to combination treatment with long-acting β-agonist (LABA) and inhaled corticosteroid (ICS) in patients with severe Chronic Obstructive Pulmonary Disease (COPD) on the rate of exacerbations defined as increase of symptoms that requires a change of medication (antibiotics and/or systemic glucocorticoid) or hospitalisation. DESIGN: Phase III multicenter, randomized, placebo-controlled, double blind, parallel, prospective study. Patient will be recruited during an hospitalisation due to COPD exacerbation and randomised at the time of discharge to receive theophylline 100 mg or placebo on top of combination therapy with inhaled corticosteroids and long-acting beta agonist. The rate of exacerbations will be determined every three months up to one year follow-up. Cl inic visits: every 3 months (total number of clinic visits = 4). In each of them, the following information will be obtained:

• Number/severity of exacerbations or hospitalisation since last clinic visit
• Compliance and side effects
• Blood sample
• Plasma levels of theophylline
• Sputum (induced)
• MMRC
• SGRQ
• Forced spirometry + inspiratory capacity \- At the beginning and at the end of the study
• 6MWT
• BMI
• BODE

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD

Outcome Measures

Primary Outcomes (1)

• Rate of exacerbations

  Rate of exacerbations defined as increase of symptoms that requires a change of medication (antibiotics and/or systemic glucocorticoid) or hospitalisation.

  1 year

Secondary Outcomes (1)

• Number of hospitalisation

  1 year

Study Arms (2)

Intervention

EXPERIMENTAL

Inhaled corticosteroids and long-acting beta agonist + theophylline (Slophylline capsules 100 mg/Theo-dur Retard 100 mg b.i.d.)

Drug: theophylline

Control

PLACEBO COMPARATOR

inhaled corticosteroids and long-acting beta agonist + Placebo

Other: placebo

Interventions

theophylline DRUG

theophylline 100 mg, twice at day

Intervention

placebo OTHER

Placebo

Control

Eligibility Criteria

• Age: 45 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is willing and able to give informed consent for participation in the study.
• Ability to understand study procedures and to comply with them for the entire length of the study.
• Any gender. No contraception is required neither pregnancy expected in the range of age
• Age \> 45 years
• Smoking history \> 10 pack-years (current or ex-smokers)
• Clinical diagnosis of COPD
• Presence of severe airflow obstruction on forced spirometry (FEV1/FVC \< 0.7 and post-BD FEV1 \< 50% of reference value) staged as GOLD III or IV
• Diagnosis of COPD exacerbation on discharge.

You may not qualify if:

• Presence or history of other chronic respiratory diseases (asthma, bronchiectasis, TB lesions)
• Cancer
• Heart failure
• Pregnancy, or risk of pregnancy
• Other inflammatory diseases
• Previous treatment with theophylline
• For drug studies: allergy/sensitivity to study drugs or their ingredients.
• Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Inability or unwillingness of individual or legal guardian/representative to give written informed consent.

Sponsors & Collaborators

• Hospital Son Espases: lead
• Spanish Research Center for Respiratory Diseases: collaborator
• Fundación Mutua Madrileña: collaborator

Study Sites (10)

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07010, Spain

Location

Hospital Universitario Nuestra Señora de la Candelaria

Santa Cruz de Tenerife, Canary Islands, 38010, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital de Sant Pau

Barcelona, 08025, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Gregorio Marañón

Madrid, 28009, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, 28044, Spain

Location

Hospital Miguel Servet

Zaragoza, 50004, Spain

Location

Related Publications (1)

• Cosio BG, Shafiek H, Iglesias A, Yanez A, Cordova R, Palou A, Rodriguez-Roisin R, Peces-Barba G, Pascual S, Gea J, Sibila O, Barnes PJ, Agusti A. Oral Low-dose Theophylline on Top of Inhaled Fluticasone-Salmeterol Does Not Reduce Exacerbations in Patients With Severe COPD: A Pilot Clinical Trial. Chest. 2016 Jul;150(1):123-30. doi: 10.1016/j.chest.2016.04.011. Epub 2016 Apr 21.

  PMID: 27107490 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Theophylline

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Borja G Cosio, MD

  Hospital Son Espases

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: May 14, 2012
• First Posted: May 16, 2012
• Study Start: January 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: September 1, 2016
• Last Updated: August 29, 2017

Record last verified: 2017-08

Locations

ES (10)