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

NCT02261727 | Completed Phase 4 Results DMC

• 2 other identifiers: TGI-Resp-011033117
• Study Type: interventional
• Target: 1,670
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Theophylline; Oral corticosteroids; COPD exacerbations

Outcome Measures

Primary Outcomes (1)

• Total COPD Exacerbation Rate

  The total number of COPD exacerbations reported within 48 weeks

  48 weeks observation; rate annualised

Secondary Outcomes (4)

• Time to First COPD Exacerbation

  Median time (days) from randomisation to first exacerbation over a 48 week period per participant

• Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)

  Change over 48 week study duration

• Post Bronchodilator FEV1

  Change at 48 weeks

• Change in COPD Assessment Test (CAT) Score

  48 weeks

Other Outcomes (1)

• Hospitalisations

  48 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo (for prednisone); Drug: Placebo (for Theophylline)

Low-dose theophylline arm

ACTIVE COMPARATOR

Theophylline 100 mg twice daily

Drug: Theophylline; Drug: Placebo (for prednisone)

Theophylline and Prednisone arm

ACTIVE COMPARATOR

Theophylline 100 mg twice daily plus prednisone 5 mg once daily

Drug: Theophylline; Drug: Prednisone

Interventions

Theophylline DRUG

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

Also known as: Theophylline (100 mg twice a day)

Low-dose theophylline arm; Theophylline and Prednisone arm

Prednisone DRUG

Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties

Also known as: Prednisone (5mg once daily), cortisone

Theophylline and Prednisone arm

Placebo (for prednisone) 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

Also known as: Prednisone placebo 1 tab once daily in arms 1 and 2

Low-dose theophylline arm; Placebo

Placebo (for Theophylline) DRUG

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

Also known as: Theophylline placebo 1 tab twice daily

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• The George Institute: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (1)

The George Institute for Global Health

Sydney, New South Wales, 2000, Australia

Location

Related Publications (1)

• 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.

  PMID: 33334939 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Theophylline; Prednisone; Cortisone

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; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenes; 17-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

There are some limitations to our study, there was a 26% withdrawal rate in this study, with a higher rate of withdrawals occurring earlier in the trial. Patients requested withdrawal if they felt the treatment was not helping them and, in particular, if they suffered an exacerbation. This was most evident at the first study visit after treatment commencement, when the greatest number of withdrawals occurred.

Results Point of Contact

• Title: Prof Christine Jenkins
• Organization: The George Institute for Global Health

christine.jenkins@sydney.edu.au

+61280524300

Study Officials

• Norbert Berend, MD

  The George Institute

  PRINCIPAL INVESTIGATOR

• Christine R Jenkins, MD

  The George Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2014
• First Posted: October 10, 2014
• Study Start: June 1, 2014
• Primary Completion: May 14, 2018
• Study Completion: May 14, 2018
• Last Updated: August 12, 2021
• Results First Posted: August 12, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)