Chronic Obstructive Pulmonary Disease (COPD).Phase 3NCT01398072
Development of an Optimal Antibiotic Regime for Long-term Therapy in Stable Chronic Obstructive Pulmonary Disease (COPD)
A Phase 3 study testing Moxifloxacin, Azithromycin and Doxycycline in people with Chronic Obstructive Pulmonary Disease (COPD)., run by University College, London at 1 site in United Kingdom.
Trial summary
Chronic Obstructive Pulmonary Disease (COPD) is the cause of considerable deaths, and exacerbations (flare up of symptoms) are a major cause of hospital admission in the UK. Bacterial infections play an important role in the development of COPD, however, there is little information available about the use of long term… Read more about this study
- Who is it for?
- Ages 45 to 80 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease (COPD).
- What is being tested?
- Moxifloxacin, Azithromycin and Doxycycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2011to Apr 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed COPD diagnosis
- Informed Consent: Patients must give their signed and dated written informed consent to participate
- Gender: Male or female patients
- Age: ≥ 45 years of age at screening
- Produce sputum regularly (produce sputum in at least 3 months of a year)
- Able to complete questionnaires for health status and symptoms and considered able to comply with the dosing regimen.
- Severity of disease: Patients with a measured FEV1<80% of predicted normal values as determined at screening. An average of three spirometry readings will be taken.
Who cannot join
- Patients with TB, other chronic respiratory disease (e.g. chronic asthma, bronchiectasis, pulmonary fibrosis), patients with hepatic or renal impairment and patients with prolonged QT interval and other cardiac abnormalities.
- Patients with known hypersensitivity to the antibiotics under evaluation.
- Patients on long term antibiotics for other conditions.
- Patients with uncontrolled hypertension.
- Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding.
- Patients with a history of long QT syndrome or whose QTc measured at Visit 1 is prolonged (>450 msec for males and females) as confirmed by the ECG assessor.
- Clinically relevant abnormal laboratory values at the screening assessment that could interfere with the objectives of the trial or safety of the volunteer.
- Patient taking clinically significant contraindicated medication, as per the SmPCs
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Academic Unit of Respiratory Medicine, Royal Free Hospital
London, NW3 2PF
Ethaar El-Emir, PhD, 0044 2073177510, ethaar.el-emir@nhs.net
Jadwiga A Wedzicha, MA, MD, FRCP
About this study
Official title: A Phase III Single-blind, Randomised Placebo Controlled Trial of Long Term Therapy in Patients With Stable COPD Using Moxifloxacin, Azithromycin and Doxycycline: a Bayesian Decision Analysis, Including Other Criteria, Will be Used to Distinguish the Optimal Antibiotic Treatment
Chronic Obstructive Pulmonary Disease (COPD) is the cause of considerable deaths, and exacerbations (flare up of symptoms) are a major cause of hospital admission in the UK. Bacterial infections play an important role in the development of COPD, 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 identify the best antibiotic regime for treating patients with COPD who have persistent bacterial infection in their lung. We will test a variety of approaches including both older and newer regimes prescribed either on a daily basis at a lower dose or in "pulsed" courses (for example, every other day or five days every month). The three antibiotics tested in this study are: moxifloxacin, azithromycin and doxycycline. This is a 13 weeks study conducted at the Royal Free Hospital, London. It is expected that approximately 200 patients will be selected for this study. The information we get from this study may help us to treat future patients with COPD better.
Read the detailed description
This is a 14 week study in which 200 patients with COPD will be selected for this study from GP practices up to a 15 mile radius from the Royal Free Hospital to participate in this study. The 3 antibiotic regimes (plus a placebo group) will be used in this study are:
Moxifloxacin: an oral dose of 400 mg once daily for 5 consecutive days every 4 weeks.
Azithromycin: an oral dose of 250 mg once daily three times a week (every other day).
Doxycycline: an oral dose of 100 mg once daily.
Placebo will be given as one table once daily.
Study recruitment and enrollment will take place through the Primary Care Research Network (PCRN). Potentially eligible participants aged ≥ 45 will be identified from GP practices up to a 15 mile radius from the RFH. Potential eligible patients will be contacted by letter with an accompanying patient information sheet (PIS) describing the study in detail and inviting the patient to attend a hospital visit and enroll. If patients have not responded to the invitation letter, this will be followed by a reminder letter approximately 2 weeks later. Non responders to the reminder letter will be followed up by a final telephone call. Patients expressing an interest in participation will be offered a screening appointment at the Royal Free Hospital. Patients will be asked to visit the hospital 3 times and will be contacted twice by telephone during the course of the study.
At the Screening Visit (V1), the following will take place:
- The study will be discussed again with the patient during this visit and if he/she agree to participate, they will be asked to sign the consent form.
- A medical history of the patient will be taken. This will include smoking history, antibiotic Hypersensitivity, as well as patient concomitant medication.
- A full physical examination will be performed and height and weight of patients will be recorded.
- A lung function test (spirometry assessment) will be performed.
- A blood sample will be collected in order to perform routine haematology/blood chemistry and liver function.
- A sputum sample will be taken and analysed to determine number of bacteria in the lung and to screen for Tuberculosis.
- A urine pregnancy test will be carried out on females of childbearing potential.
- Patients will be asked to complete two sets of questionnaires; "St. George's respiratory questionnaire" (SGRQ) which includes simple questions about the patients COPD condition and how it affects their life; the second an EQ5D questionnaire which includes simple questions relating to the general quality of their life.
- Patients will be given daily diary cards and asked to record their symptoms.
- An ECG will be performed on all patients.
If patients are eligible for the trial, they will be randomised to one of the following groups:
Moxifloxacin: an oral dose of 400 mg once daily for 5 consecutive days every 4 weeks for a total duration of 13 weeks.
Azithromycin: an oral dose of 250 mg once daily three times a week (every other day) for a total duration of 13 weeks.
Doxycycline: an oral dose of 100 mg once daily, for a total duration of 13 weeks Placebo: an oral daily dose of one capsule, for a total duration of 13 weeks.
This is a single-blind trial. Patients will be blinded to treatment; the investigator will be unblinded. Microbiologists will also be blind to treatment allocation when assessing sputum samples.
Following randomisation of eligible patients, patients will be asked to return to the hospital for a second visit (within 1 week) to collect their medication from the research fellow who will instruct the patient to start taking the medication within 3 days. At this visit, the research team will check if patients are happy filling in their diary cards and will be happy to answer any questions they may have.
In week 5 and week 9 of treatment, each patient will be contacted by telephone to:
- Monitor progress and compliance.
- Remind patients to take medication.
- Encourage patients to contact the GP/investigator if symptoms worsen.
- The occurrence of any adverse effects/serious adverse effects (AE/SAE) or an exacerbation will be checked and recorded.
- Remind patients to fill in their daily diary cards
End of Study Visit (at week 14):
Patients will be asked to return to the hospital and the following assessments will be made:
- The occurrence of AE/SAE or exacerbations will be checked and recorded.
- A spirometry assessment to test their lung function.
- Diary cards will be collected by the investigator.
- SGRQ and EQ5D questionnaires will be completed at this visit by the patient.
- A sputum sample will be taken from the patients to determine bacterial number in their lung.
- Unused study medication and packaging will be collected from the patient.
- Being tested
- Moxifloxacin, Azithromycin, Doxycycline, Placebo
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MoxifloxacinDrug
An oral dose of 400 mg once daily for 5 consecutive days every 4 weeks.
AzithromycinDrug
An oral dose of 250 mg once daily three times a week (every other day).
DoxycyclineDrug
An oral dose of 100 mg once daily.
PlaceboDrug
Oral dose of one table once daily.
| Study group | Role | What they receive |
|---|---|---|
| Moxifloxacin | Active comparator | Not described Receives: Drug: Moxifloxacin |
| Azithromycin | Active comparator | Not described Receives: Drug: Azithromycin |
| Doxycycline | Active comparator | Not described Receives: Drug: Doxycycline |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure and compare reduction in the concentration of lower airway bacteria in patients with COPD between three different antibiotic regimes and placebo
Measured: Week 14 post treatment
Secondary outcomes (1)
To measure changes in lung function measure, health status and exacerbations.
Measured: week 14 post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2011 (estimated)
- Study startDec 2011
- Primary completionJan 2013 (estimated)
- Study completionApr 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary Disease (COPD).Studies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Free Hampstead NHS Trust, University of Cambridge, National Institute for Health Research, United Kingdom
- Investigators
- Jadwiga A Wedzicha, Principal investigator, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01398072
- Sponsor's protocol ID
- 11/0078
- Status last verified
- May 2012
- First submitted
- 18 Jul 2011
- Last updated
- 1 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Brill SE, Law M, El-Emir E, Allinson JP, James P, Maddox V, Donaldson GC, McHugh TD, Cookson WO, Moffatt MF, Nazareth I, Hurst JR, Calverley PM, Sweeting MJ, Wedzicha JA. Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial. Thorax. 2015 Oct;70(10):930-8. doi: 10.1136/thoraxjnl-2015-207194. Epub 2015 Jul 15.
PubMed 26179246
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Single-blind, Randomised Placebo Controlled Trial of Long Term Therapy in Patients With Stable COPD Using Moxifloxacin, Azithromycin and Doxycycline: a Bayesian Decision Analysis, Including Other Criteria, Will be Used to Distinguish the Optimal Antibiotic Treatment
- ClinicalTrials.gov ID
- NCT01398072
- Acronym / sponsor ID
- 11/0078
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Royal Free Hampstead NHS Trust, University of Cambridge, National Institute for Health Research, United Kingdom
- Study start
- Dec 2011
- Primary completion
- Jan 2013 (estimated)
- Study completion
- Apr 2013 (estimated)
- First posted
- 20 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic Obstructive Pulmonary Disease (COPD) is the cause of considerable deaths, and exacerbations (flare up of symptoms) are a major cause of hospital admission in the UK. Bacterial infections play an important role in the development of COPD, 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 identify the best antibiotic regime for treating patients with COPD who have persistent bacterial infection in their lung. We will test a variety of approaches including both older and newer regimes prescribed either on a daily basis at a lower dose or in "pulsed" courses (for example, every other day or five days every month). The three antibiotics tested in this study are: moxifloxacin, azithromycin and doxycycline. This is a 13 weeks study conducted at the Royal Free Hospital, London. It is expected that approximately 200 patients will be selected for this study. The information we get from this study may help us to treat future patients with COPD better.
Detailed description
This is a 14 week study in which 200 patients with COPD will be selected for this study from GP practices up to a 15 mile radius from the Royal Free Hospital to participate in this study. The 3 antibiotic regimes (plus a placebo group) will be used in this study are:
Moxifloxacin: an oral dose of 400 mg once daily for 5 consecutive days every 4 weeks.
Azithromycin: an oral dose of 250 mg once daily three times a week (every other day).
Doxycycline: an oral dose of 100 mg once daily.
Placebo will be given as one table once daily.
Study recruitment and enrollment will take place through the Primary Care Research Network (PCRN). Potentially eligible participants aged ≥ 45 will be identified from GP practices up to a 15 mile radius from the RFH. Potential eligible patients will be contacted by letter with an accompanying patient information sheet (PIS) describing the study in detail and inviting the patient to attend a hospital visit and enroll. If patients have not responded to the invitation letter, this will be followed by a reminder letter approximately 2 weeks later. Non responders to the reminder letter will be followed up by a final telephone call. Patients expressing an interest in participation will be offered a screening appointment at the Royal Free Hospital. Patients will be asked to visit the hospital 3 times and will be contacted twice by telephone during the course of the study.
At the Screening Visit (V1), the following will take place:
- The study will be discussed again with the patient during this visit and if he/she agree to participate, they will be asked to sign the consent form.
- A medical history of the patient will be taken. This will include smoking history, antibiotic Hypersensitivity, as well as patient concomitant medication.
- A full physical examination will be performed and height and weight of patients will be recorded.
- A lung function test (spirometry assessment) will be performed.
- A blood sample will be collected in order to perform routine haematology/blood chemistry and liver function.
- A sputum sample will be taken and analysed to determine number of bacteria in the lung and to screen for Tuberculosis.
- A urine pregnancy test will be carried out on females of childbearing potential.
- Patients will be asked to complete two sets of questionnaires; "St. George's respiratory questionnaire" (SGRQ) which includes simple questions about the patients COPD condition and how it affects their life; the second an EQ5D questionnaire which includes simple questions relating to the general quality of their life.
- Patients will be given daily diary cards and asked to record their symptoms.
- An ECG will be performed on all patients.
If patients are eligible for the trial, they will be randomised to one of the following groups:
Moxifloxacin: an oral dose of 400 mg once daily for 5 consecutive days every 4 weeks for a total duration of 13 weeks.
Azithromycin: an oral dose of 250 mg once daily three times a week (every other day) for a total duration of 13 weeks.
Doxycycline: an oral dose of 100 mg once daily, for a total duration of 13 weeks Placebo: an oral daily dose of one capsule, for a total duration of 13 weeks.
This is a single-blind trial. Patients will be blinded to treatment; the investigator will be unblinded. Microbiologists will also be blind to treatment allocation when assessing sputum samples.
Following randomisation of eligible patients, patients will be asked to return to the hospital for a second visit (within 1 week) to collect their medication from the research fellow who will instruct the patient to start taking the medication within 3 days. At this visit, the research team will check if patients are happy filling in their diary cards and will be happy to answer any questions they may have.
In week 5 and week 9 of treatment, each patient will be contacted by telephone to:
- Monitor progress and compliance.
- Remind patients to take medication.
- Encourage patients to contact the GP/investigator if symptoms worsen.
- The occurrence of any adverse effects/serious adverse effects (AE/SAE) or an exacerbation will be checked and recorded.
- Remind patients to fill in their daily diary cards
End of Study Visit (at week 14):
Patients will be asked to return to the hospital and the following assessments will be made:
- The occurrence of AE/SAE or exacerbations will be checked and recorded.
- A spirometry assessment to test their lung function.
- Diary cards will be collected by the investigator.
- SGRQ and EQ5D questionnaires will be completed at this visit by the patient.
- A sputum sample will be taken from the patients to determine bacterial number in their lung.
- Unused study medication and packaging will be collected from the patient.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Moxifloxacin | Active comparator | Drug: Moxifloxacin |
| Azithromycin | Active comparator | Drug: Azithromycin |
| Doxycycline | Active comparator | Drug: Doxycycline |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Confirmed COPD diagnosis
- Informed Consent: Patients must give their signed and dated written informed consent to participate
- Gender: Male or female patients
- Age: ≥ 45 years of age at screening
- Produce sputum regularly (produce sputum in at least 3 months of a year)
Key exclusion criteria (8 listed)
- Patients with TB, other chronic respiratory disease (e.g. chronic asthma, bronchiectasis, pulmonary fibrosis), patients with hepatic or renal impairment and patients with prolonged QT interval and other cardiac abnormalities.
- Patients with known hypersensitivity to the antibiotics under evaluation.
- Patients on long term antibiotics for other conditions.
- Patients with uncontrolled hypertension.
- Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MoxifloxacinAn oral dose of 400 mg once daily for 5 consecutive days every 4 weeks. | Drug | Moxifloxacin |
| AzithromycinAn oral dose of 250 mg once daily three times a week (every other day). | Drug | Azithromycin |
| DoxycyclineAn oral dose of 100 mg once daily. | Drug | Doxycycline |
| PlaceboOral dose of one table once daily. | Drug | Placebo |
Primary outcome
To measure and compare reduction in the concentration of lower airway bacteria in patients with COPD between three different antibiotic regimes and placebo
Time frame: Week 14 post treatment
1 secondary outcome
To measure changes in lung function measure, health status and exacerbations.
Time frame: week 14 post treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2012.
- Derived from this study: PubMed 26179246Brill SE, Law M, El-Emir E, Allinson JP, James P, Maddox V, Donaldson GC, McHugh TD, Cookson WO, Moffatt MF, Nazareth I, Hurst JR, Calverley PM, Sweeting MJ, Wedzicha JA. Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial. Thorax. 2015 Oct;70(10):930-8. doi: 10.1136/thoraxjnl-2015-207194. Epub 2015 Jul 15.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jadwiga A Wedzicha principal investigator
University College, London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Moxifloxacin, Azithromycin and Doxycycline in people with Chronic Obstructive Pulmonary Disease (COPD)., run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ethaar El-Emir, PhD (0044 2073177510, ethaar.el-emir@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To measure and compare reduction in the concentration of lower airway bacteria in patients with COPD between three different antibiotic regimes and placebo (time frame: Week 14 post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01398072, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2012.