Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study

NCT ID: NCT02261727

Last Updated: 2021-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1670 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2018-05-14

Brief Summary

The aim of this multi-centre, double blind, randomised, controlled trial (DBRCT) is to assess the effect of low dose theophylline, singly and in combination with low dose oral prednisone, on COPD (Chronic Obstructive Pulmonary Disease) exacerbations, quality of life and secondary clinical outcomes compared with usual therapy and placebo over 48 weeks of treatment. 1670 symptomatic patients with COPD will be recruited in China for comparison of low dose theophylline versus placebo and low dose theophylline + low dose prednisone The primary end-point for this study is the annualised COPD exacerbation rate between the treatment groups. Secondary outcomes included time to first severe exacerbation requiring hospitalisation or death, health status, and pre- and post-bronchodilator spirometry.

Detailed Description

The investigators hypothesise that patients with COPD will have beneficial responses to low dose theophylline and prednisone, superior to placebo and low dose theophylline alone, reflected by a range of clinical outcomes.

The study aims to demonstrate that treatment with low dose oral prednisone and low dose, slow release theophylline compared to low dose, slow release theophylline only or placebo will reduce COPD exacerbations and improve a range of secondary outcomes including quality of life, COPD Assessment Test (CAT) score, hospital admissions and lung function.

Eligible participants will be randomised to one of three treatment arms in a DBRCT and will receive placebo OR low-dose theophylline (100 mg twice a day) OR low-dose theophylline 100 mg twice a day (BD) plus low-dose prednisone (5 mg once a day)

Patients will be eligible for inclusion if all the following criteria are met:

• Current or former smokers (>10 pack years) or biomass exposure
• 40 - 80 years of age
• Clinical diagnosis of COPD
• Post-bronchodilator forced expiratory volume at one second (FEV1) <70% predicted
• Post bronchodilator FEV1/forced vital capacity (FVC) ratio<0.7

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

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

Study Groups

Placebo

Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily

Group Type: PLACEBO_COMPARATOR

Placebo (for prednisone)

Intervention Type: DRUG

• Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily
• Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily

Placebo (for Theophylline)

Intervention Type: DRUG

One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)

Low-dose theophylline arm

Theophylline 100 mg twice daily

Group Type: ACTIVE_COMPARATOR

Theophylline

Intervention Type: DRUG

Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor

Placebo (for prednisone)

Intervention Type: DRUG

• Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily
• Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily

Theophylline and Prednisone arm

Theophylline 100 mg twice daily plus prednisone 5 mg once daily

Group Type: ACTIVE_COMPARATOR

Theophylline

Intervention Type: DRUG

Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor

Prednisone

Intervention Type: DRUG

Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties

Interventions

Theophylline

Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor

Intervention Type: DRUG

Prednisone

Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties

Intervention Type: DRUG

Placebo (for prednisone)

• Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily
• Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily

Intervention Type: DRUG

Placebo (for Theophylline)

One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)

Intervention Type: DRUG

Other Intervention Names

Theophylline (100 mg twice a day); Prednisone (5mg once daily); cortisone; Prednisone placebo 1 tab once daily in arms 1 and 2; Theophylline placebo 1 tab twice daily

Eligibility Criteria

Inclusion Criteria

• Current or former smokers (> 10 pack years) or biomass exposure
• 40 - 80 years of age
• Clinical diagnosis of COPD
• Post-bronchodilator FEV1 < 70% predicted
• Post bronchodilator FEV1/FVC ratio < 0.7

Exclusion Criteria

• Life expectancy of less than 12 months
• Exacerbation or respiratory infection within 4 weeks prior to randomisation
• Patient is taking and requires maintenance oral corticosteroids
• Patient is on domiciliary oxygen
• There has been previous pulmonary resection
• Previous sensitivity to, or intolerance of theophylline
• Coexistent illness precluding participation in the study (epilepsy, chronic liver disease, unstable cardiovascular disease, diabetes, active malignancy)
• Inability to complete quality of life questionnaire
• Concomitant major illness that would interfere with visits, assessments and follow-up
• Have evidence of chronic liver disease, or transaminase or gamma-glutamyltransferase (GGT) elevation > 1.5 x upper limit of normal (ULN)
• Random blood glucose level > 8mmol/L
• High chance in the view of the treating physician that the patient will not adhere to study treatment and follow up

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Health and Medical Research Council, Australia

OTHER

Sponsor Role: collaborator

The George Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Norbert Berend, MD

Role: PRINCIPAL_INVESTIGATOR

The George Institute

Christine R Jenkins, MD

Role: PRINCIPAL_INVESTIGATOR

The George Institute

Locations

The George Institute for Global Health

Sydney, New South Wales, Australia

Countries

Australia

References

Jenkins CR, Wen FQ, Martin A, Barnes PJ, Celli B, Zhong NS, Zheng JP, Scaria A, Di Tanna GL, Bradbury T, Berend N; TASCS study investigators. The effect of low-dose corticosteroids and theophylline on the risk of acute exacerbations of COPD: the TASCS randomised controlled trial. Eur Respir J. 2021 Jun 10;57(6):2003338. doi: 10.1183/13993003.03338-2020. Print 2021 Jun.

Reference Type: DERIVED

PMID: 33334939 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1033117

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

TGI-Resp-01

Identifier Type: -

Identifier Source: org_study_id