Clinical trial NCT01599871: Low-dose Theophylline as Anti-inflammatory Enhancer in Severe Chronic Obstructive Pulmonary Disease
Official title: Multicenter 52 Weeks Double Blind Placebo-controlled Trial for the Assessment of Theophylline on Top of Combination Therapy in Severe COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Lead sponsor: Hospital Son Espases
Sponsor class: OTHER
Collaborators: name: Spanish Research Center for Respiratory Diseases
name: Fundación Mutua Madrileña
First posted: 2012-05-16
Enrollment: 70
Sex: ALL
Minimum age (years): 45
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Rate of exacerbations
timeFrame: 1 year
Secondary outcomes:
measure: Number of hospitalisation
timeFrame: 1 year
Other outcomes:
Locations:
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Baleares
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario Nuestra Señora de la Candelaria
state: Islas Canarias
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
affiliation: Hospital Son Espases
name: Borja G Cosio, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.