Trial Outcomes & Findings for Azithromycin in Bronchiolitis Obliterans Syndrome (NCT NCT01009619)

NCT ID: NCT01009619

Last Updated: 2011-10-03

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 83 participants
• Primary outcome timeframe: 2 years post-transplant
• Results posted on: 2011-10-03

Participant Flow

Participant milestones

Measure	Azithromycin 250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study	Placebo Placebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Overall Study STARTED	40	43
Overall Study COMPLETED	40	43
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Azithromycin in Bronchiolitis Obliterans Syndrome

Baseline characteristics by cohort

Measure	Azithromycin n=40 Participants 250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study	Placebo n=43 Participants Placebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.	Total n=83 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	38 Participants n=5 Participants	42 Participants n=7 Participants	80 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age Continuous	51.2 years STANDARD_DEVIATION 0 • n=5 Participants	50.9 years STANDARD_DEVIATION 0 • n=7 Participants	51.1 years STANDARD_DEVIATION 0 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	20 Participants n=7 Participants	37 Participants n=5 Participants
Region of Enrollment Belgium	40 participants n=5 Participants	43 participants n=7 Participants	83 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years post-transplant

Population: intention to treat analysis

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.

Outcome measures

Measure	Azithromycin n=40 Participants 250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study	Placebo n=43 Participants Placebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Prevalence of Bronchiolitis Obliterans Syndrome (BOS)	5 participants Interval 0.0 to 0.0	19 participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: 2 years post-transplant

Population: intention to treat

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.

Outcome measures

Measure	Azithromycin n=40 Participants 250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study	Placebo n=43 Participants Placebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Overall Survival	6 participants	8 participants

SECONDARY outcome

Timeframe: 2 years post-transplant

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.

Outcome measures

Measure	Azithromycin n=40 Participants 250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study	Placebo n=43 Participants Placebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Acute Rejection Incidence Rate	0.86 incidence rate (events/person per year) Standard Deviation 1.53	0.78 incidence rate (events/person per year) Standard Deviation 1.17

SECONDARY outcome

Timeframe: 2 years post-transplant

Population: intention to treat

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.

Outcome measures

Measure	Azithromycin n=40 Participants 250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study	Placebo n=43 Participants Placebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Infection Incidence Rate	0.95 incidence rate (events/person per year) Standard Deviation 1.4	0.73 incidence rate (events/person per year) Standard Deviation 1.42

SECONDARY outcome

Timeframe: during first two years post-transplant

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.

Outcome measures

Measure	Azithromycin n=40 Participants 250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study	Placebo n=43 Participants Placebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Pulmonary Function	81.11 percent predicted Standard Deviation 20.31	75.28 percent predicted Standard Deviation 25.31

SECONDARY outcome

Timeframe: during first two years post-transplant

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.

Outcome measures

Measure	Azithromycin n=40 Participants 250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study	Placebo n=43 Participants Placebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Broncho-alveolar (BAL) Neutrophilia	9.68 percent cells Standard Deviation 18.20	15.73 percent cells Standard Deviation 25.36

SECONDARY outcome

Timeframe: during the first two years post-transplant

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.

Outcome measures

Measure	Azithromycin n=40 Participants 250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study	Placebo n=43 Participants Placebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Plasma C-reactive Protein (CRP) Levels	7.06 mg/L Standard Deviation 16.97	10.02 mg/L Standard Deviation 17.51

Adverse Events

Azithromycin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Azithromycin n=40 participants at risk 250 mg daily for 5 days, followed by 250 mg three times a week (Mon.-Wed.-Fri.) until the end of study	Placebo n=43 participants at risk Placebo daily for 5 days, followed by placebo three times a week (Mon.-Wed.-Fri.) until end of study.
Gastrointestinal disorders nausea and diarrhea after intake of study drug	7.5% 3/40 • Number of events 3 • 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. Definition for adverse events: Serious adverse events: allergic (rash, urticaria, Stevens-Johnson syndrome, angioneurotic edema or anaphylaxis), cardiac (ventricular tachycardia or Torsades de Pointes), neurologic (convulsions). Other adverse events: gastro-intestinal (nausea, dyspepsia, pain or cramps, diarrhea or pseudomembranous colitis).	0.00% 0/43 • 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. Definition for adverse events: Serious adverse events: allergic (rash, urticaria, Stevens-Johnson syndrome, angioneurotic edema or anaphylaxis), cardiac (ventricular tachycardia or Torsades de Pointes), neurologic (convulsions). Other adverse events: gastro-intestinal (nausea, dyspepsia, pain or cramps, diarrhea or pseudomembranous colitis).

Additional Information

Prof. Dr. GM Verleden

Katholieke Universiteit Leuven and University Hospital Leuven

Phone: +32 16 34 68 08

Email: geert.verleden@uzleuven.be

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place