Lymphocytic Bronchi(Oli)Tis Post-lung TransplantationPhase 4AZI002NCT01109160
Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation
A Phase 4 study testing Azithromycin Dihydrate in people with Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation, run by KU Leuven at 1 site in Belgium.
Trial summary
This study investigates the role of azithromycin treatment for lymphocytic bronchitis/bronchiolitis after lung transplantation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation
- What is being tested?
- Azithromycin Dihydrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteBelgium
- Study dates
- Apr 2010to Jul 2013
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent
- Adult (age at least 18 years old at moment of transplantation)
- Able to take oral medication
- Histologic diagnosis of lymphocytic bronchiolitis or bronchitis ('grade B') without concurrent acute cellular allograft rejection 'grade A' ≥2
Who cannot join
- Severe suture problems (e.g. airway stenosis) requiring lasering or stenting
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Open-label Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation
This study investigates the role of azithromycin treatment for lymphocytic bronchitis/bronchiolitis after lung transplantation.
Read the detailed description
Lymphocytic bronchitis/bronchiolitis is one of the major risk factors for development of chronic rejection/BOS after lung transplantation. There is currently no established treatment available for this condition. There is now mounting evidence that IL-17 producing lymphocytes (TH17) not only participate in chronic allograft rejection/BOS, but are also present within the airway wall during lymphocytic bronchiolitis and that IL-17 mRNA-levels in bronchoalveolar lavage fluid of these patients are upregulated. As such, TH17 may account for the increased BAL neutrophilia seen in these patients, as IL-17 may be responsible for driving IL-8 secretion (a neutrophil-attracting chemokine) from various cell types in the airways. Since azithromycin has previously been shown to reduce both IL-17 induced IL-8 production by human airway smooth muscle cells 'in vitro' and bronchoalveolar IL-8/neutrophil levels in LTx recipients with established BOS, we believe that azithromycin has great potential for treating lymphocytic bronchi(oli)tis by attenuating this TH17/IL-17/IL-8-mediated airway inflammation, possibly even halting the subsequent development of chronic rejection/BOS after lung transplantation. In this study, histologic, spirometric, bronchoalveolar an radiologic features will be investigated in patients treated with confirmed lymphocytic bronchitis/bronchiolitis treated with azithromycin.
- Being tested
- Azithromycin Dihydrate
- Keywords
- azithromycin, lymphocytic bronchitis or bronchiolitis, lung transplantation, acute allograft rejection, chronic allograft rejection, bronchiolitis obliterans syndrome
- Medical subject headings
- Bronchiolitis, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin DihydrateDrug
Also called Azithromycin 250 mg, ZTM250, Zitromax TM (ATC J01FA10)
Add-on of study-drug (azithromycin) to 'standard of care' at diagnosis of lymphocytic bronchi(oli)tis.
Study-drug regime: 250 mg daily for 5 days, followed by 250 mg every other day until the end of the study-period (6 months treatment).
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin | Experimental | Add-on of study-drug (azithromycin) to 'standard of care': 250 mg daily for 5 days, followed by 250 mg every other day until the end of the study-period (6 months treatment). Receives: Drug: Azithromycin Dihydrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Histology on bronchial and/or transbronchial biopsies
Evolution of lymphocytic airway inflammation after 3 months of treatment
Measured: after 3 months of treatment
Pulmonary function (FEV1)
Evolution of FEV1 after 3 months of treatment
Measured: after 3 months of treatment
Bronchoalveolar cellularity and protein levels (IL-8, IL-17)
Evolution of bronchoalveolar cellularity and protein levels (IL-8, IL-17) after 3 months of treatment
Measured: after 3 months of treatment
Radiologic features
Evolution of radiologic features (e.g. tree-in-bud, consolidation, bronchiectasis, air trapping, etc.) on chest X-ray or HRCT after 3 months of treatment
Measured: after 3 months of treatment
Secondary outcomes (1)
Pulmonary function (FEV1)
Evolution of FEV1 after 6 months of treatment
Measured: after 6 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionOct 2012
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Lymphocytic Bronchi(Oli)Tis Post-lung TransplantationStudies of the same condition, open and under way.
- More trials run by KU LeuvenThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- Fund for Scientific Research, Flanders, Belgium
- Responsible party
- Principal investigator, GM. Verleden, KU Leuven
- Investigators
- Geert M Verleden, MD, PhD, Principal investigator, KULeuven and UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01109160
- Sponsor's protocol ID
- AZI002
- Other IDs
- 2010-018724-16
- Acronym
- AZI002
- Status last verified
- Jul 2013
- First submitted
- 21 Apr 2010
- Last updated
- 4 Jul 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Vanaudenaerde BM, De Vleeschauwer SI, Vos R, Meyts I, Bullens DM, Reynders V, Wuyts WA, Van Raemdonck DE, Dupont LJ, Verleden GM. The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant. 2008 Sep;8(9):1911-20. doi: 10.1111/j.1600-6143.2008.02321.x.
PubMed 18786233Vanaudenaerde BM, Wuyts WA, Geudens N, Dupont LJ, Schoofs K, Smeets S, Van Raemdonck DE, Verleden GM. Macrolides inhibit IL17-induced IL8 and 8-isoprostane release from human airway smooth muscle cells. Am J Transplant. 2007 Jan;7(1):76-82. doi: 10.1111/j.1600-6143.2006.01586.x. Epub 2006 Oct 25.
PubMed 17061983Vanaudenaerde BM, Dupont LJ, Wuyts WA, Verbeken EK, Meyts I, Bullens DM, Dilissen E, Luyts L, Van Raemdonck DE, Verleden GM. The role of interleukin-17 during acute rejection after lung transplantation. Eur Respir J. 2006 Apr;27(4):779-87. doi: 10.1183/09031936.06.00019405.
PubMed 16585086Verleden GM, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE. Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2006 Sep 1;174(5):566-70. doi: 10.1164/rccm.200601-071OC. Epub 2006 Jun 1.
PubMed 16741151
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Open-label Study of Azithromycin for Lymphocytic Bronchiolitis/Bronchitis After Lung Transplantation
- ClinicalTrials.gov ID
- NCT01109160
- Acronym / sponsor ID
- AZI002 / AZI002
- Keywords
- azithromycin, lymphocytic bronchitis or bronchiolitis, lung transplantation, acute allograft rejection, chronic allograft rejection, bronchiolitis obliterans syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- KU LeuvenUniversity, hospital or other
- Collaborators
- Fund for Scientific Research, Flanders, Belgium
- Study start
- Apr 2010
- Primary completion
- Oct 2012 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 23 Apr 2010 (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.
This study investigates the role of azithromycin treatment for lymphocytic bronchitis/bronchiolitis after lung transplantation.
Detailed description
Lymphocytic bronchitis/bronchiolitis is one of the major risk factors for development of chronic rejection/BOS after lung transplantation. There is currently no established treatment available for this condition. There is now mounting evidence that IL-17 producing lymphocytes (TH17) not only participate in chronic allograft rejection/BOS, but are also present within the airway wall during lymphocytic bronchiolitis and that IL-17 mRNA-levels in bronchoalveolar lavage fluid of these patients are upregulated. As such, TH17 may account for the increased BAL neutrophilia seen in these patients, as IL-17 may be responsible for driving IL-8 secretion (a neutrophil-attracting chemokine) from various cell types in the airways. Since azithromycin has previously been shown to reduce both IL-17 induced IL-8 production by human airway smooth muscle cells 'in vitro' and bronchoalveolar IL-8/neutrophil levels in LTx recipients with established BOS, we believe that azithromycin has great potential for treating lymphocytic bronchi(oli)tis by attenuating this TH17/IL-17/IL-8-mediated airway inflammation, possibly even halting the subsequent development of chronic rejection/BOS after lung transplantation. In this study, histologic, spirometric, bronchoalveolar an radiologic features will be investigated in patients treated with confirmed lymphocytic bronchitis/bronchiolitis treated with azithromycin.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azithromycin | Experimental | Drug: Azithromycin DihydrateAdd-on of study-drug (azithromycin) to 'standard of care': 250 mg daily for 5 days, followed by 250 mg every other day until the end of the study-period (6 months treatment). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Signed informed consent
- Adult (age at least 18 years old at moment of transplantation)
- Able to take oral medication
- Histologic diagnosis of lymphocytic bronchiolitis or bronchitis ('grade B') without concurrent acute cellular allograft rejection 'grade A' ≥2
Key exclusion criteria (1 listed)
- Severe suture problems (e.g. airway stenosis) requiring lasering or stenting
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 |
|---|---|---|
| Azithromycin DihydrateAlso: Azithromycin 250 mg, ZTM250, Zitromax TM (ATC J01FA10)Add-on of study-drug (azithromycin) to 'standard of care' at diagnosis of lymphocytic bronchi(oli)tis. Study-drug regime: 250 mg daily for 5 days, followed by 250 mg every other day until the end of the study-period (6 months treatment). | Drug | Azithromycin |
Primary outcome
Histology on bronchial and/or transbronchial biopsies
Time frame: after 3 months of treatment
Evolution of lymphocytic airway inflammation after 3 months of treatment
Pulmonary function (FEV1)
Time frame: after 3 months of treatment
Evolution of FEV1 after 3 months of treatment
Bronchoalveolar cellularity and protein levels (IL-8, IL-17)
Time frame: after 3 months of treatment
Evolution of bronchoalveolar cellularity and protein levels (IL-8, IL-17) after 3 months of treatment
Radiologic features
Time frame: after 3 months of treatment
Evolution of radiologic features (e.g. tree-in-bud, consolidation, bronchiectasis, air trapping, etc.) on chest X-ray or HRCT after 3 months of treatment
1 secondary outcome
Pulmonary function (FEV1)
Time frame: after 6 months of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jul 2013.
- Background: PubMed 18786233Vanaudenaerde BM, De Vleeschauwer SI, Vos R, Meyts I, Bullens DM, Reynders V, Wuyts WA, Van Raemdonck DE, Dupont LJ, Verleden GM. The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant. 2008 Sep;8(9):1911-20. doi: 10.1111/j.1600-6143.2008.02321.x.
- Background: PubMed 17061983Vanaudenaerde BM, Wuyts WA, Geudens N, Dupont LJ, Schoofs K, Smeets S, Van Raemdonck DE, Verleden GM. Macrolides inhibit IL17-induced IL8 and 8-isoprostane release from human airway smooth muscle cells. Am J Transplant. 2007 Jan;7(1):76-82. doi: 10.1111/j.1600-6143.2006.01586.x. Epub 2006 Oct 25.
- Background: PubMed 16585086Vanaudenaerde BM, Dupont LJ, Wuyts WA, Verbeken EK, Meyts I, Bullens DM, Dilissen E, Luyts L, Van Raemdonck DE, Verleden GM. The role of interleukin-17 during acute rejection after lung transplantation. Eur Respir J. 2006 Apr;27(4):779-87. doi: 10.1183/09031936.06.00019405.
- Background: PubMed 16741151Verleden GM, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE. Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2006 Sep 1;174(5):566-70. doi: 10.1164/rccm.200601-071OC. Epub 2006 Jun 1.
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.
Geert M Verleden, MD, PhD principal investigator
KULeuven and UZ Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azithromycin Dihydrate in people with Lymphocytic Bronchi(Oli)Tis Post-lung Transplantation, run by KU Leuven at 1 site in Belgium.
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 4 inclusion and 1 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: finished, as of the sponsor's last update on 4 Jul 2013. 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 Belgium. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histology on bronchial and/or transbronchial biopsies (time frame: after 3 months of treatment). The study lists 4 primary outcomes in all. 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 NCT01109160, which also lists 4 linked publications.
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 4 Jul 2013.