TWICS - Theophylline with Inhaled Corticosteroids

A randomised, double-blind placebo controlled trial of the effectiveness of low dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease - TWICS - Theophylline with Inhaled Corticosteroid

Status

Active, not recruiting

Phases

Phase 3Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2013-001490-25-GB

Enrollment

1424

Registered

2013-08-13

Start date

2013-08-08

Completion date

Unknown

Last updated

2019-06-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 16.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Interventions

Trade Name: Theophylline Product Name: Theophylline Pharmaceutical Form: Prolonged-release tablet INN or Proposed INN: Theophylline CAS

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Aged = 40 years. • A smoking history of at least 10 pack years. • An established predominant respiratory diagnosis of COPD (post bronchodilator FEV1/FVC=65 years) yes F.1.3.1 Number of subjects for this age range 724

Exclusion criteria

Exclusion criteria: • Severe or unstable ischaemic heart disease. • A predominant respiratory disease other than COPD. • Any other significant disease/disorder which, in the investigator’s opinion, either puts the patient at risk because of study participation or may influence the results of the study or the patient's ability to participate in the study. • Previous allocation of a randomisation code in the study or current participation in another interventional clinical study. • Theophylline use currently. • Known or suspected hypersensitivity to theophylline. • Current use of drugs known to interact with theophylline and/or increase serum theophylline: antimicrobials: aciclovir, clarithromiycin, ciprofloxacin, erythromycin, fluconazole, ketoconazole, levofloxacin, norfloxacin; cardiovascular: diltiazem, mexiletine, pentoxifylline, verapamil; neurological: bupropion, disulfiram, fluvoxamine, lithium; hormonal: medroxyprogesterone, oestrogens; immunological: methotrexate, peginterferon alpha, tacrolimus; miscellaneous: cimetidine, deferasirox, febuxostat, roflumilast, thiabendazole. • For women, current pregnancy or breast-feeding, or planned pregnancy during the study.

Design outcomes

Primary

Measure	Time frame
Timepoint(s) of evaluation of this end point: Approximately 12 months after entry into the trial.;Main Objective: The primary objective is to determine whether adding low-dose theophylline to existing treatment (inhaled corticosteroid therapy) in patients who have chronic obstructive pulmonary disease will reduce the number of exacerbations (or flare-ups) of the condition. If the treatment is effective, we will also assess whether it is cost effective.;Secondary Objective: The secondary research objectives are to compare: - hospital admissions with a primary diagnosis of exacerbation of COPD - emergency hospital admissions - lung functon - all-cause and respiratory mortality - drug reactions and serious adverse events - health related quality of life - disease specific health status - total inhaled corticosteroid dose/useage - heath care utilisiation - incremental cost-per-exacerbation avoided - lifetime cost effectiveness based on extrapolation modelling - modelled lifetime incemental cost per Quality Adjusted Life Year;Primary end point(s): The primary clinical outcome measure will be the total number of exacerbations of COPD necessitating changes in management (minimum management change - use of oral corticosteroids and/or antibiotics) during the one year treatment period, as reported by the participant. The primary economic outcome measure will be cost-per-QALY gained during the one year treatment period.	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: Approximately 12 months after entry into the trial.;Main Objective: The primary objective is to determine whether adding low-dose theophylline to existing treatment (inhaled corticosteroid therapy) in patients who have chronic obstructive pulmonary disease will reduce the number of exacerbations (or flare-ups) of the condition. If the treatment is effective, we will also assess whether it is cost effective.;Secondary Objective: The secondary research objectives are to compare: - hospital admissions with a primary diagnosis of exacerbation of COPD - emergency hospital admissions - lung functon - all-cause and respiratory mortality - drug reactions and serious adverse events - health related quality of life - disease specific health status - total inhaled corticosteroid dose/useage - heath care utilisiation - incremental cost-per-exacerbation avoided - lifetime cost effectiveness based on extrapolation modelling - modelled lifetime incemental cost per Quality Adjusted Life Year;Primary end point(s): The primary clinical outcome measure will be the total number of exacerbations of COPD necessitating changes in management (minimum management change - use of oral corticosteroids and/or antibiotics) during the one year treatment period, as reported by the participant. The primary economic outcome measure will be cost-per-QALY gained during the one year treatment period.

—

Secondary

Measure	Time frame
Secondary end point(s): • Total number of COPD exacerbations requiring hospital admission. • Total number of emergency hospital admissions (all causes). • Post bronchodilator lung function (FEV1, FVC). • All-cause and respiratory mortality. • Serious adverse events, adverse reactions. • Total dose of inhaled corticosteroid. • Utilisation of primary or secondary health care for respiratory events • Disease specific health status using the COPD Assessment Test (CAT). • The Hull Airways Reflux Questionnaire (HARQ) will be used at some sites to collect data on respiratory and GI symptoms. • Generic health related quality of life using EuroQoL 5D (EQ-5D) Index. • Modelled lifetime incremental cost per Quality Adjusted Life Year.;Timepoint(s) of evaluation of this end point: Approximately 12 months after entry into the trial.	—

Measure

Time frame

Secondary end point(s): • Total number of COPD exacerbations requiring hospital admission. • Total number of emergency hospital admissions (all causes). • Post bronchodilator lung function (FEV1, FVC). • All-cause and respiratory mortality. • Serious adverse events, adverse reactions. • Total dose of inhaled corticosteroid. • Utilisation of primary or secondary health care for respiratory events • Disease specific health status using the COPD Assessment Test (CAT). • The Hull Airways Reflux Questionnaire (HARQ) will be used at some sites to collect data on respiratory and GI symptoms. • Generic health related quality of life using EuroQoL 5D (EQ-5D) Index. • Modelled lifetime incremental cost per Quality Adjusted Life Year.;Timepoint(s) of evaluation of this end point: Approximately 12 months after entry into the trial.

—

Countries

United Kingdom

Contacts

Public ContactSeonaidh Cotton

University of Aberdeen

s.c.cotton@abdn.ac.uk01224438178

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Mar 17, 2026