Effects of Long Term Antibiotic Therapy on Exacerbation Rate in Stable COPD Patients

A Phase III Double-blind, Randomised, Placebo Controlled Trial of Long Term Therapy on Exacerbation Rate in Patients With Stable COPD Using Doxycycline

This study investigates if long term use of the antibiotic doxycycline can reduce exacerbations in COPD patients. Half of the patients will receive doxycycline which the other half will receive a placebo.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Doxycycline; Drug: Placebo

Detailed Description

Chronic Obstructive Pulmonary Disease (COPD) is a common disease which can place a considerable burden on people who suffer from it. COPD exacerbations (periods when symptoms flare up) are a major cause of hospital admission in the UK. Bacterial infections play an important role in the development of COPD and so one possible treatment for COPD is with antibiotics. However, there is little information available about the use of long term antibiotics in the treatment of this disease.

Therefore, the purpose of this study is to investigate if long term use of the antibiotic Doxycycline can reduce exacerbations and improve the outlook for these patients.

• Study Type: Interventional
• Enrollment (Actual): 222
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L9 7AL
    • Aintree University Hospital NHS Foundation Trust
  • London, United Kingdom, SW17 0RE
    • St Georges University Hospitals NHS Foundation Trust
  • London, United Kingdom, SW36NP
    • Royal Brompton and Harefield Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent given
• Confirmed COPD diagnosis
• Severity of disease: Patients with a measured FEV1<80% of predicted normal values.
• At least one treated exacerbation (Patient recalls an episode of symptomatic worsening which was treated and was consistent with a COPD exacerbation) in the previous year.
• Age: ≥ 45 years of age at screening.
• Able to complete questionnaires for health status and symptoms and considered able to comply with the dosing regimen.
• Patients willing to report exacerbations and attend for study visits.

Exclusion Criteria:

• Patients with a known diagnosis of active TB or other chronic respiratory disease in the judgement of the study doctor.
• Hepatic or renal impairment as defined as LFTs > 5XULN, and eGFR<30 ml/min/1.73m2.
• Patients with known hypersensitivity to Tetracyclines, the IMP and/or Placebo including their excipients.
• Patients taking ongoing antibiotic therapy for COPD or other conditions.
• Patients with uncontrolled clinically significant hypertension
• Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding.
• Patients with uncontrolled clinically relevant bradycardia, cardiac arrhythmias or cardiac insufficiency.
• Clinically relevant abnormal electrolyes (sodium or potassium), renal function (urea and creatinine) or liver function (ALT, AST, ALP) that could interfere with the objectives of the trial or safety of the volunteer.
• Patient taking clinically significant contraindicated medication, as per the SmPC for Doxycycline.
• Use of another experimental investigational medicinal product within 3 months of study enrolment. If the IMP used was as part of the NIHR WP2 study then entry to WP3 after a 6 week washout period is permissible.
• Patients with any other condition precluding enrolment in the trial, according to the assessment of the study doctor. This will be documented at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Doxycycline; Doxycycline: oral dose of 100 mg once daily, for a total duration of 52 weeks.	Drug: Doxycycline; An oral dose of 100 mg of Doxycycline once daily, for a total duration of 52 weeks.
Placebo Comparator: Placebo; Placebo: an oral dose of one capsule once daily, for a total duration of 52 weeks.	Drug: Placebo; An oral dose of one capsule of placebo once daily, for a total duration of 52 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of exacerbations (per person/year) recorded from date of drug issue until date of end of treatment visit.	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Lung function (spirometry) (FEV1, FVC, FEV1/FVC ratio, FEV1 as % Predicted).	12 months of treatment
Total and individual component (symptoms, activity, impact) SGRQ scores will be used to measure health status.	12 months of treatment
Respiratory health status across groups as measured from total number of symptoms in a day and prevalence of individual symptoms recorded on daily diary cards.	12 months of treatment
Airway bacteria numbers taken from a sputum sample, provided by a subset of patients, at months 3, 6, 9, 12 after drug issue.	12 months of treatment
Changes in C-reactive protein (CRP) levels from baseline.	12 months of treatment
Hospital admissions. This data will be collected from Hospital Episode Statistics (HES).	12 months of treatment
Time to 1st exacerbation measured by diary cards in both therapy and placebo groups.	12 months of treatment
Rate of exacerbations treated with steroids and antibiotics.	12 months of treatment
Adherence as measured using pill counts.	12 months of treatment
Antibiotic resistance measured in the subset of patients (able to produce sputum) from sputum based on standard NHS procedures (not resistant, intermediate, severe, resistant).	12 months of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-specified Exploratory Subgroup Analysis	As co-morbidities for COPD are heterogeneous, exploratory analysis will be carried out to investigate whether there is an interaction with treatment- i.e. to investigate whether outcomes of treatment are either influenced by and/or restricted to patients with particular known co morbidities. The following will be looked at in this study: Cardiovascular disease. This included patients receiving treatment for Ischemic Heart Disease, hypertension and heart failure. Diabetes and/or known impaired glucose intolerance Body Mass Index (BMI)	12 months of treatment

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Wisia Wedzicha, MD, Imperial College London

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): July 12, 2017
• Study Completion (Actual): July 12, 2017

Study Registration Dates

• First Submitted: November 20, 2014
• First Submitted That Met QC Criteria: November 28, 2014
• First Posted (Estimate): December 3, 2014

Study Record Updates

• Last Update Posted (Actual): July 26, 2017
• Last Update Submitted That Met QC Criteria: July 24, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: 14IC2030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO