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

NCT02305940 | Completed Phase 3 DMC

• 1 other identifier: 14IC2030
• Study Type: interventional
• Target: 222
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Outcome Measures

Primary Outcomes (1)

• Rate of exacerbations (per person/year) recorded from date of drug issue until date of end of treatment visit.

  12 months

Secondary Outcomes (10)

• 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

Other Outcomes (1)

• Pre-specified Exploratory Subgroup Analysis

  12 months of treatment

Study Arms (2)

Doxycycline

ACTIVE COMPARATOR

Doxycycline: oral dose of 100 mg once daily, for a total duration of 52 weeks.

Drug: Doxycycline

Placebo

PLACEBO COMPARATOR

Placebo: an oral dose of one capsule once daily, for a total duration of 52 weeks.

Drug: Placebo

Interventions

Doxycycline DRUG

An oral dose of 100 mg of Doxycycline once daily, for a total duration of 52 weeks.

Doxycycline

Placebo DRUG

An oral dose of one capsule of placebo once daily, for a total duration of 52 weeks

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (3)

Aintree University Hospital NHS Foundation Trust

Liverpool, L9 7AL, United Kingdom

Location

St Georges University Hospitals NHS Foundation Trust

London, SW17 0RE, United Kingdom

Location

Royal Brompton and Harefield Hospital NHS Foundation Trust

London, SW36NP, United Kingdom

Location

Related Publications (1)

• Allinson JP, Vlies BH, Brill SE, Law M, Burnside G, Finney LJ, Alves-Moreira L, Donaldson GC, Calverley PMA, Walker PP, Wedzicha JA. A Double-Blind, Randomized, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2023 Sep 1;208(5):549-558. doi: 10.1164/rccm.202212-2287OC.

  PMID: 37450935 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Doxycycline

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)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Wisia Wedzicha, MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2014
• First Posted: December 3, 2014
• Study Start: July 1, 2014
• Primary Completion: July 12, 2017
• Study Completion: July 12, 2017
• Last Updated: July 26, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)