Targeted Retreatment of COPD Exacerbations

Targeted Retreatment of Incompletely Recovered COPD Exacerbations With Ciprofloxacin: a Double-blind, Randomised, Placebo-controlled, Multicentre Phase III Trial

This study investigates the effects of targeted re-treatment of patients who do not recover from an exacerbation of COPD. Half of the patients will receive ciprofloxacin while the other half will receive a placebo.

Study Overview

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

Detailed Description

COPD is a long term lung condition where patients suffer recurrent symptom flare-ups, called 'exacerbations'. Patients who have lots of exacerbations have a worse quality of life, poorer ability to breath, and may die earlier than those who don't. Previous research by our group has shown that patients who have an exacerbation and have not completely recovered two weeks after the start of treatment are more likely to suffer another one early than those who completely recover.

This study aims to test whether we can prevent this early re-exacerbation by giving an extra course of antibiotics, compared to a placebo. Patients who experience an exacerbation of COPD and are treated with antibiotics will, two weeks after the start of their treatment, be invited to attend a screening visit. Patients will be eligible for the study if they have not fully recovered at this visit (i.e. if they either still have symptoms or if blood tests show there is still inflammation present) and fulfil other diagnostic measures for COPD. Patients will be allocated to the treatment groups at random, and if eligible will be treated with a further 1 week of ciprofloxacin 500mg twice daily or a placebo.

Patients will then be followed up in the study for a further 3 months, and the primary study outcome will be the time to the next exacerbation.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L9 7AL
    • Aintree University Hospital NHS Foundation Trust
  • London, United Kingdom, W2 1NY
    • St Mary's Hospital
  • 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:

1. Diagnosis of COPD confirmed spirometrically at screening
2. COPD exacerbation with treatment commenced 14 days prior to study enrolment and treated with 5-14 days of a non-quinolone antibiotic.
3. Exacerbation here will be defined as an episode of symptomatic worsening of COPD that was treated by the patient's attending clinician. Confirmation of the initial exacerbation diagnosis will be provided from the case notes, referral letter, or directly from the treating clinician, and will be documented in the CRF.
4. Age: ≥ 45 years of age at screening.
5. Persistent symptoms and/or a CRP≥8mg/L when assessed 2 weeks after exacerbation onset
6. Able to complete questionnaires for health status and symptoms and keep written diary cards
7. Severity of disease: Patients with a measured FEV1<80% of predicted normal values at 2 weeks post exacerbation
8. Able and willing to give signed and dated written informed consent to participate.

Exclusion Criteria:

1. Other clinically predominant chronic respiratory disease.
2. Intubated and receiving mechanical ventilation
3. Patients with known hypersensitivity to the antibiotic under evaluation, to other quinolones or any excipients of the IMP/placebo.
4. Patients with a prior history of tendonopathy or tendon rupture
5. Elderly patients taking long term systemic corticosteroids
6. Patients on long term antibiotics for other conditions
7. Patient too unwell for randomisation, i.e. requiring retreatment in the judgment of the study doctor
8. Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding.
9. Patient taking clinically significant contraindicated medication as per the SmPC s, such as use of concomitant tizanidine or methotrexate.

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: Ciprofloxacin; 500 mg, twice daily for 1 week (oral).	Drug: Ciprofloxacin; 500 mg, twice daily for 1 week (oral)
Placebo Comparator: Placebo; one capsule, twice daily for 1 week.	Drug: Placebo; One capsule, twice daily for 1 week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the Next COPD Exacerbation	The primary outcome will be the time to the next COPD exacerbation following targeted retreatment with the IMP or placebo, censored at 90 days.	Up to 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of the Initial Exacerbation	Secondary endpoints will include duration of the initial exacerbation following targeted retreatment with the IMP or placebo.	Up to 90 days
Number of Participants With Serious Non Fatal Adverse Events	Secondary endpoints will include adverse events following targeted retreatment with the IMP or placebo.	7 days of treatment
Changes in Lung Function	Secondary endpoints will include changes from randomization to 90 days in FEV1.	Baseline and 90 days
Number of Participants Who Have Resistance Bacteria in the Sputum	Bacterial load and resistance Secondary endpoints will include resistance following targeted retreatment with the IMP or placebo.	Up to 90 days
Hospital Readmission	Secondary endpoints will include hospital readmission following targeted retreatment with the IMP or placebo.	90 days of treatment

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Ritchie AI, Brill SE, Vlies BH, Finney LJ, Allinson JP, Alves-Moreira L, Wiseman DJ, Walker PP, Baker E, Elkin SL, Mallia P, Law M, Donaldson GC, Calverley PMA, Wedzicha JA. Targeted Retreatment of Incompletely Recovered Chronic Obstructive Pulmonary Disease Exacerbations with Ciprofloxacin. A Double-Blind, Randomized, Placebo-controlled, Multicenter, Phase III Clinical Trial. Am J Respir Crit Care Med. 2020 Aug 15;202(4):549-557. doi: 10.1164/rccm.201910-2058OC.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2014
• Primary Completion (Actual): January 22, 2019
• Study Completion (Actual): January 22, 2019

Study Registration Dates

• First Submitted: November 20, 2014
• First Submitted That Met QC Criteria: November 20, 2014
• First Posted (Estimate): November 24, 2014

Study Record Updates

• Last Update Posted (Actual): March 8, 2021
• Last Update Submitted That Met QC Criteria: February 16, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary Disease (COPD)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Ciprofloxacin
• Other Study ID Numbers: 14IC2031; 2012-002198-72 (EudraCT Number)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No