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

Sponsor

Hospital Son Espases (Other)

Overall Status

Completed

CT.gov ID

NCT01599871

Collaborator

Spanish Research Center for Respiratory Diseases (Other), Fundación Mutua Madrileña (Other)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: theophylline Other: placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Multicenter 52 Weeks Double Blind Placebo-controlled Trial for the Assessment of Theophylline on Top of Combination Therapy in Severe COPD

Study Start Date :

Jan 1, 2011

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Inhaled corticosteroids and long-acting beta agonist + theophylline (Slophylline capsules 100 mg/Theo-dur Retard 100 mg b.i.d.)	Drug: theophylline theophylline 100 mg, twice at day
Placebo Comparator: Control inhaled corticosteroids and long-acting beta agonist + Placebo	Other: placebo Placebo

Arm

Intervention/Treatment

Experimental: Intervention

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

Drug: theophylline

theophylline 100 mg, twice at day

Placebo Comparator: Control

inhaled corticosteroids and long-acting beta agonist + Placebo

Other: placebo

Placebo

Outcome Measures

Primary Outcome Measures

Rate of exacerbations [1 year]
Rate of exacerbations defined as increase of symptoms that requires a change of medication (antibiotics and/or systemic glucocorticoid) or hospitalisation.

Secondary Outcome Measures

Number of hospitalisation [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Son Espases	Palma de Mallorca	Baleares	Spain	07010
2	Hospital Universitario Nuestra Señora de la Candelaria	Santa Cruz de Tenerife	Islas Canarias	Spain	38010
3	Clínica Universitaria de Navarra	Pamplona	Navarra	Spain	31008
4	Hospital del Mar	Barcelona		Spain	08003
5	Hospital de Sant Pau	Barcelona		Spain	08025
6	Hospital Clínic de Barcelona	Barcelona		Spain	08036
7	Hospital Gregorio Marañón	Madrid		Spain	28009
8	Fundación Jiménez Díaz	Madrid		Spain	28040
9	Hospital 12 de Octubre	Madrid		Spain	28044
10	Hospital Miguel Servet	Zaragoza		Spain	50004