A Phase 4 interventional study of Azithromycin and Placebo in Bronchiolitis Obliterans Syndrome, Graft Rejection and Lymphocytic Bronchiolitis, sponsored by KU Leuven. Completed at 1 site in Belgium. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2011-10-03.
Sponsored by KU Leuven · Phase 4, Interventional, and Prevention
Preventive treatment with azithromycin reduces the prevalence fo Bronchiolitis Obliterans Syndrome after lung transplantation.
360 studies on the registry are indexed under Bronchiolitis; 43 are open to participants now.
This study's enrollment of 83 is close to the median of 80 across 249 interventional studies indexed under Bronchiolitis.
Browse Bronchiolitis studies →KU Leuven is the lead sponsor of 358 studies on the registry; 62 are open to participants now.
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Exclusion Criteria:
250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study
Drug: Azithromycin
PLacebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Drug: Placebo
Azithromycin 250 mg daily during 5 days followed by 250 mg three times a week on Mon., Wed. and Fri. during study-period.
Also known as: Zitromax (Azithromycin Dihydrate, Pfizer, ZTM250)
Placebo once daily during 5 days, followed by one placebo three times a week on Mon., Wed. and Fri during rest of study-period.
Also known as: Lactose monohydricum Ph.Eur. (Fagron)
Prevalence of Bronchiolitis Obliterans Syndrome (BOS)
BOS was defined as a sustained decrease in forced Expiratory Volume in one second (FEV1) of at least 20% from the patient's maximum post-operative values in the absence of other causes.
Time frame: 2 years post-transplant
Overall Survival
Survival data were obtained using all-cause mortality information in the Leuven University Hospital transplant database, in which all our lung transplant recipients since 1991 are registered. For the end-point of all-cause mortality, survival times were not censored at retransplantation or at study-discontinuation if these preceded death, or else at 2 years after transplantation.
Time frame: 2 years post-transplant
Acute Rejection Incidence Rate
Bronchoscopy and broncho-alveolar lavage (BAL) was routinely performed at discharge, 3, 6, 12, 18, 24 months post-transplantation and later at intervals of 1 year, or in case of clinically suspected acute allograft rejection, infection or chronic rejection. Transbronchial biopsies were routinely performed at discharge and 3 months post-transplant or in case of suspected acute rejection, infection or chronic rejection. Biopsies were graded according to the 1996 ISHLT-guidelines (grade A0-4 with concomitant B0-4), as well as assessed for other interstitial lesions of the pulmonary graft.
Time frame: 2 years post-transplant
Infection Incidence Rate
Cytomegalovirus (CMV)-status was assessed on on every broncho-alevolar lavage sample and by serum CMV DNA at weekly intervals during hospitalization and thereafter at each outpatient evaluation or hospital admission. Immunohistochemical staining for CMV was performed on transbronchial biopsies in case of clinical suspicion of infection (i.e. dyspnea, cough, sputum, fever, increased plasma C-reactive protein, new chest radiograph infiltrates, or a decrease of at least 10% in peak expiratory flow (PEF) as measured by patient's peak flow measurements.
Time frame: 2 years post-transplant
Pulmonary Function
Spirometry (Masterscreen, Jaeger, Hoechberg, Germany) was performed at twice weekly intervals for the first 2 postoperative months, thereafter at weekly to biweekly intervals until 6 months post-transplantation, then every 2 to 4 weeks until the first postoperative year and afterwards life-long at intervals of 2 to 3 months according to American Thoracic Society standards and forced expiratory volume in one second (FEV1) expressed in terms of the percentage of predicted values.
Time frame: during first two years post-transplant
Broncho-alveolar (BAL) Neutrophilia
BAL was performed with two 50 mL aliquots of sterile saline at room temperature. Five mL of the recovered BAL fluid was sent for microbiological and virological assessment, whereas the remaining fluid was analysed for cell counts after a cytospin was made in a Shandon cytocentrifuge and stained with May-Grünwald-Giemsa. Differential cell counts were determined by counting at least 300 cells.
Time frame: during first two years post-transplant
Plasma C-reactive Protein (CRP) Levels
Plasma C-reactive protein (CRP) levels were assessed using Tina-quant CRP latex assay, Roche, Mannheim, Germany; sensitivity threshold of 1 mg/L, upper limit of normal 5 mg/L.
Time frame: during the first two years post-transplant
| Milestone | Azithromycin | Placebo |
|---|---|---|
| Started | 40 | 43 |
| Completed | 40 | 43 |
| Not completed | 0 | 0 |
BOS was defined as a sustained decrease in forced Expiratory Volume in one second (FEV1) of at least 20% from the patient's maximum post-operative values in the absence of other causes.
| participants | Azithromycin | Placebo |
|---|---|---|
| Prevalence of Bronchiolitis Obliterans Syndrome (BOS) | 5 (0 to 0) | 19 (0 to 0) |
Survival data were obtained using all-cause mortality information in the Leuven University Hospital transplant database, in which all our lung transplant recipients since 1991 are registered. For the end-point of all-cause mortality, survival times were not censored at retransplantation or at study-discontinuation if these preceded death, or else at 2 years after transplantation.
| participants | Azithromycin | Placebo |
|---|---|---|
| Overall Survival | 6 | 8 |
Bronchoscopy and broncho-alveolar lavage (BAL) was routinely performed at discharge, 3, 6, 12, 18, 24 months post-transplantation and later at intervals of 1 year, or in case of clinically suspected acute allograft rejection, infection or chronic rejection. Transbronchial biopsies were routinely performed at discharge and 3 months post-transplant or in case of suspected acute rejection, infection or chronic rejection. Biopsies were graded according to the 1996 ISHLT-guidelines (grade A0-4 with concomitant B0-4), as well as assessed for other interstitial lesions of the pulmonary graft.
| incidence rate (events/person per year) | Azithromycin | Placebo |
|---|---|---|
| Acute Rejection Incidence Rate | 0.86 ± 1.53 | 0.78 ± 1.17 |
Cytomegalovirus (CMV)-status was assessed on on every broncho-alevolar lavage sample and by serum CMV DNA at weekly intervals during hospitalization and thereafter at each outpatient evaluation or hospital admission. Immunohistochemical staining for CMV was performed on transbronchial biopsies in case of clinical suspicion of infection (i.e. dyspnea, cough, sputum, fever, increased plasma C-reactive protein, new chest radiograph infiltrates, or a decrease of at least 10% in peak expiratory flow (PEF) as measured by patient's peak flow measurements.
| incidence rate (events/person per year) | Azithromycin | Placebo |
|---|---|---|
| Infection Incidence Rate | 0.95 ± 1.4 | 0.73 ± 1.42 |
Spirometry (Masterscreen, Jaeger, Hoechberg, Germany) was performed at twice weekly intervals for the first 2 postoperative months, thereafter at weekly to biweekly intervals until 6 months post-transplantation, then every 2 to 4 weeks until the first postoperative year and afterwards life-long at intervals of 2 to 3 months according to American Thoracic Society standards and forced expiratory volume in one second (FEV1) expressed in terms of the percentage of predicted values.
| percent predicted | Azithromycin | Placebo |
|---|---|---|
| Pulmonary Function | 81.11 ± 20.31 | 75.28 ± 25.31 |
BAL was performed with two 50 mL aliquots of sterile saline at room temperature. Five mL of the recovered BAL fluid was sent for microbiological and virological assessment, whereas the remaining fluid was analysed for cell counts after a cytospin was made in a Shandon cytocentrifuge and stained with May-Grünwald-Giemsa. Differential cell counts were determined by counting at least 300 cells.
| percent cells | Azithromycin | Placebo |
|---|---|---|
| Broncho-alveolar (BAL) Neutrophilia | 9.68 ± 18.20 | 15.73 ± 25.36 |
Plasma C-reactive protein (CRP) levels were assessed using Tina-quant CRP latex assay, Roche, Mannheim, Germany; sensitivity threshold of 1 mg/L, upper limit of normal 5 mg/L.
| mg/L | Azithromycin | Placebo |
|---|---|---|
| Plasma C-reactive Protein (CRP) Levels | 7.06 ± 16.97 | 10.02 ± 17.51 |
Collected over A study-nurse verified compliance and possible adverse events at each contact with patients during routine follow-up visits at the outpatient clinic or hospital-admissions during the first two years post-transplant.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Azithromycin | — | 0/40 (0%) | 3/40 (7.5%) |
| Placebo | — | 0/43 (0%) | 0/43 (0%) |
| Event | Azithromycin | Placebo |
|---|---|---|
| nausea and diarrhea after intake of study drugGastrointestinal disorders | 3/40 | 0/43 |
| Age, Categorical(Participants) | Azithromycin | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 38 | 42 | 80 |
| >=65 years | 2 | 1 | 3 |
| Age Continuous(years) | Azithromycin | Placebo | Total |
|---|---|---|---|
| Mean | 51.2 ± 0 | 50.9 ± 0 | 51.1 ± 0 |
| Sex: Female, Male(Participants) | Azithromycin | Placebo | Total |
|---|---|---|---|
| Female | 23 | 23 | 46 |
| Male | 17 | 20 | 37 |
| Region of Enrollment(participants) | Azithromycin | Placebo | Total |
|---|---|---|---|
| Belgium | 40 | 43 | 83 |
This study is completed, as verified in Aug 2011. You cannot join it, but the record below documents what was studied.
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