Clinical Trial Results:
A PROSPECTIVE, RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF
PRE-TRANSPLANT AND PROMPT POST-TRANSPLANT TREATMENT WITH AZITHROMYCIN TO IMPROVE EARLY ALLOGRAFT FUNCTION AND OUTCOME AFTER LUNG TRANSPLANTATION
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Summary
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EudraCT number |
2012-003331-32 |
Trial protocol |
BE |
Global end of trial date |
07 Apr 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Dec 2020
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First version publication date |
16 Dec 2020
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Other versions |
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Summary report(s) |
Final results AZI0003 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AZI003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01915082 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
KU Leuven
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Sponsor organisation address |
49 Herestraat , Leuven, Belgium, B-3000
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Public contact |
Dr. Robin Vos
Dr. Bart Vanaudenaerde, Lab of Pneumology, KULeuven, +32 1633 01 94, bart.vanaudenaerde@med.kuleuven.be
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Scientific contact |
Dr. Robin Vos
Dr. Bart Vanaudenaerde, Lab of Pneumology, KULeuven, +32 1633 01 94, robin.vos@uzleuven.be
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Jun 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Apr 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Apr 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Improvement in mean pulmonary function (FEV1; %pred) during the first 3 months after lung transplantation
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Protection of trial subjects |
Routine post-transplant follow-up, immunosuppressive regimen and infectious prophylaxis was given to all patients according to standardized protocols, independent of study drug.
Adverse events were monitored by the treating LTx clinician (blinded for study-drug) and were defined as hearing loss, cardiac arrhythmias (e.g. torsade de pointes), serious allergic reactions including skin reactions (rash, urticaria or Stevens-Johnson syndrome), angioneurotic edema and anaphylaxis and neurologic disorders (convulsions).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Oct 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 68
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Worldwide total number of subjects |
68
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EEA total number of subjects |
68
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
68
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||
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Pre-assignment
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Screening details |
120 patients who underwent double LTx between October 2013 and October 2015 were screened for inclusion. | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Azithromycin | |||||||||
Arm description |
Study drug was added to standard of care and was administered once immediately before LTx (1000 mg of azithromycin or placebo) and every other day from day 1 until day 31 after LTx (250 mg of azithromycin or placebo). | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
azithromycin
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Investigational medicinal product code |
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Other name |
Zitromax® oral suspension 200 mg/ 5 mL
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Pharmaceutical forms |
Suspension for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Zitromax® oral suspension 200 mg/ 5 mL
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Arm title
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PLacebo | |||||||||
Arm description |
Ora-plus (97% purified water, <1% Sodium phosphate monobasic, <1% Sodium carboxymethylcellulose, <1% Microcrystalline cellulose, <1% Xanthan gum, <1% Carrageenan) | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Ora-plus
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Ora-plus (97% purified water, <1% Sodium phosphate monobasic, <1% Sodium carboxymethylcellulose, <1% Microcrystalline cellulose, <1% Xanthan gum, <1% Carrageenan) suspension
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End points reporting groups
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Reporting group title |
Azithromycin
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Reporting group description |
Study drug was added to standard of care and was administered once immediately before LTx (1000 mg of azithromycin or placebo) and every other day from day 1 until day 31 after LTx (250 mg of azithromycin or placebo). | ||
Reporting group title |
PLacebo
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Reporting group description |
Ora-plus (97% purified water, <1% Sodium phosphate monobasic, <1% Sodium carboxymethylcellulose, <1% Microcrystalline cellulose, <1% Xanthan gum, <1% Carrageenan) | ||
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End point title |
Pulmonary function | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
3 months after transplant
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Statistical analysis title |
Statistical analysis | ||||||||||||
Statistical analysis description |
Patient proportions were compared using the chi-squaretest. Continuous data are presented as mean and standard error ofthe mean when normally distributed, or as a median with inter-quartile range when non‒normally distributed. Group means werecompared using unpaired, two-tailedt-test or Mann−WhitneyU-test for normally or non‒normally distributed variables, respectively. GraphPad Prism 6.0 software (GraphPad) was used for statistical analysis. p-values are two-sided, with p<0.05 significant.
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Comparison groups |
Azithromycin v PLacebo
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Number of subjects included in analysis |
68
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
At every patient contact during the study period, minimum at least every 4 months
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Adverse event reporting additional description |
None of the previously defined adverse events were reported in either the study or placebo group.
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Assessment type |
Systematic | |||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
placebo
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Reporting group description |
- | |||||||||||||||
Reporting group title |
azithromycin
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Reporting group description |
- | |||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | ||||||||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No predefined adverse events were recorded |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/30686699 |
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