Disorder Related to Lung TransplantationPhase 4AZI003NCT01915082
Peri-operative Azithromycin to Improve Early Allograft Function and Outcome After Lung Transplantation
A Phase 4 study testing Azithromycin and Ora-Plus in people with Disorder Related to Lung Transplantation, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
This study investigates possible beneficial effects of peri-operative treatment (i.e. pre-transplant initiation and prompt post-transplant continuation) with azithromycin in lung transplantation. Our hypothesis is that this therapy will improve early allograft function and outcome following human lung transplantation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Disorder Related to Lung Transplantation
- What is being tested?
- Azithromycin and Ora-Plus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteBelgium
- Study dates
- Sep 2013to Oct 2015
- 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)
- Single lung transplantation, sequential single (double) lung transplantation or heart-lung transplantation
Who cannot join
- Known previous allergy for azithromycin (including skin reactions such as rash, urticaria or Stevens- Johnson syndrome, angioneurotic oedema and anaphylaxis)
- Retransplantation or multi-organ (other than heart-lung) transplantation
- Inclusion in Transmedics® Organ Care System (OCS™ LUNG) study (OCS-LUN-03-2010)(S53795).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
This study investigates possible beneficial effects of peri-operative treatment (i.e. pre-transplant initiation and prompt post-transplant continuation) with azithromycin in lung transplantation. Our hypothesis is that this therapy will improve early allograft function and outcome following human lung transplantation.
Read the detailed description
After a lung transplant recipient is put on the waiting list for subsequent lung transplantation, informed consent will be sought for the current study. If signed informed is obtained, the patient will be enrolled upon admission for transplantation at which moment he/she will be randomised to placebo or azithromycin according to a blinded randomisation-list. In accordance with his/her attributed study-number, each included patient will be assigned to a pre-numbered bottle containing the study-drug, which was pre-filled and blinded for its content and are delivered in advance to the ward by the University Leuven Hospital Pharmacy. From this bottle, a first loading dose of placebo (25 mL po syrup) or azithromycin (25 mL po syrup = 1000 mg) will be given by the nurse during preparation for subsequent lung transplantation (Day 0). After lung transplantation, 'add on' treatment of placebo (6.25 mL) or azithromycin (6.25 mL = 250 mg) syrup will be given via (naso)gastric tube or per os every other day (days 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 and 31) by the nurses taking care of the patient in the early post-transplant period. In case of any serious suspected drug-interactions (however very unlikely) or adverse attributable to the study drug, the study will be promptly stopped in this patient. Serious adverse events will be monitored by the treating lung transplant physicians (blinded for the study-drug) and are defined as allergic reactions including skin reactions (rash, urticaria or Stevens-Johnson syndrome), angioneurotic edema and anaphylaxis, cardiac arrhythmias (ventricular tachycardia or torsades de pointes), neurologic disorders (convulsions). Routine immunosuppressive, prophylactic and necessary antimicrobial treatment according to standardized protocol is given to all patients, independent of study drug. After transplantation, routine follow-up (e.g. biochemical and microbiological blood analyses, chest radiography, pulmonary function testing and bronchoscopic evaluation with broncho-alveolar lavage and/or trans- or endobronchial biopsies will be performed as they are currently routinely being performed as part of the standard, prospective follow-up after lung transplantation.
- Conditions
- Disorder Related to Lung Transplantation
- Being tested
- Azithromycin, Ora-Plus
- Keywords
- Lung Function, Allograft Outcome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
Also called Zithromax®
Zithromax® oral suspension 200 mg/ 5 mL (Pfizer, UK):
Zithromax® 1000 mg syrup per os once at recipient intake for lung transplantation (day 0); followed by Zithromax® 250 mg syrup via (naso)gastric tube or per os every other day until one month after lung transplantation (days 1,3,5,7,9,11,13,15, 17,19,21,23,25,27,29 and 31).
Ora-PlusDrug
Also called Ora-Plus®
Ora-Plus® oral suspension (Paddock Laboratories, 3940 Quebec Avenue N, Minneapolis, MN 55427, USA; NDC-number: 0574-0303-16):
Ora-Plus® 25mL syrup per os once at recipient intake for lung transplantation (day 0); followed by Ora-Plus® 6.25 mL syrup via (naso)gastric tube or per os every other day until one month after lung transplantation (days 1,3,5,7,9,11,13,15, 17,19,21,23,25,27,29 and 31).
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin | Experimental | A first dose of azithromycin (25 mL po syrup = 1000 mg) will be given during preparation for subsequent lung transplantation (Day 0).
After lung transplantation, 'add on' treatment of azithromycin (6.25 mL = 250 mg) syrup will be given via (naso)gastric tube or per os every other day (days 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 and 31). Receives: Drug: Azithromycin |
| Ora-Plus | Placebo comparator | A first dose of placebo (25 mL po syrup) will be given during preparation for subsequent lung transplantation (Day 0).
After lung transplantation, 'add on' treatment of placebo (6.25 mL) syrup will be given via (naso)gastric tube or per os every other day (days 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 and 31). Receives: Drug: Ora-Plus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean forced expiratory volume at one second (FEV1, %pred)
Mean FEV1 (%pred) during the first 3 months after lung transplantation (measured at discharge; thereafter twice weekly until 8 weeks post-transplant and weekly from 8 to 12 weeks post-transplant; i.e. total estimated number of 14 spirometries per patient)
Measured: at 3 months after lung transplantation
Secondary outcomes (13)
Length of intubation
Measured: at 1 month after lung transplantation
Length of Intensive Care Unit (ICU) stay
Measured: at 3 months after lung transplantation
Length of hospital stay
Measured: at 3 months after lung transplantation
Partial Pressure of Oxygen in Arterial Blood over fraction of inspired oxygen fraction - ratio (PaO2/FiO2)
Measured: at 0, 24, 48 and 72 hours after lung transplantation
Primary graft dysfunction (PGD) prevalence and score
Measured: at 0, 24, 48 and 72 hours after lung transplantation
6-minute walking distance
Measured: at 1 month after lung transplantation
Acute rejection (grade A; grade B) prevalence/severity
Measured: at 1, 3 and 6 months after lung transplantation
Broncho-alveolar lavage neutrophilia and cytokine/protein profile
Measured: at day 1 and at 1, 3 and 6 months after lung transplantation
Airway colonization
Presence (i.e. growth) of Pseudomonas species or Aspergillus species in routine cultures of broncho-alveolar lavage fluid at day 1 and 1, 3 and 6 months after lung transplantation.
Measured: at day 1 and 1, 3 and 6 months after lung transplantation
Plasma C-reactive protein levels
Measured: at day 1, 3, 5, 7, 14 and 1, 3 and 6 months after lung transplantation
Mortality
Measured: at 1, 3 and 6 months after lung transplantation
Ventilator-free days
days alive and free from mechanical ventilation
Measured: at 6 months after transplantation
Mean forced expiratory volume at one second (FEV1, %pred)
Mean FEV1 (%pred) during the first 6 months after lung transplantation
Measured: at 6 months after lung transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2013 (estimated)
- Study startSep 2013
- Primary completionOct 2015
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 Disorder Related to Lung TransplantationStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen 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
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- Fund for Scientific Research, Flanders, Belgium, KU Leuven
- Responsible party
- Sponsor
- Investigators
- Robin Vos, MD, PhD, Principal investigator, UZ and KULeuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01915082
- Sponsor's protocol ID
- AZI003
- Other IDs
- 2012-003331-32
- Acronym
- AZI003
- Status last verified
- Sep 2013
- First submitted
- 4 Jul 2013
- Last updated
- 11 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Van Herck A, Frick AE, Schaevers V, Vranckx A, Verbeken EK, Vanaudenaerde BM, Sacreas A, Heigl T, Neyrinck AP, Van Raemdonck D, Dupont LJ, Yserbyt J, Verleden SE, Verleden GM, Vos R. Azithromycin and early allograft function after lung transplantation: A randomized, controlled trial. J Heart Lung Transplant. 2019 Mar;38(3):252-259. doi: 10.1016/j.healun.2018.12.006. Epub 2018 Dec 14.
PubMed 30686699
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01915082
- Acronym / sponsor ID
- AZI003 / AZI003
- Conditions
- Disorder Related to Lung Transplantation
- Keywords
- Lung Function, Allograft Outcome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- Fund for Scientific Research, Flanders, Belgium, KU Leuven
- Study start
- Sep 2013
- Primary completion
- Oct 2015 (actual)
- First posted
- 2 Aug 2013 (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 possible beneficial effects of peri-operative treatment (i.e. pre-transplant initiation and prompt post-transplant continuation) with azithromycin in lung transplantation. Our hypothesis is that this therapy will improve early allograft function and outcome following human lung transplantation.
Detailed description
After a lung transplant recipient is put on the waiting list for subsequent lung transplantation, informed consent will be sought for the current study. If signed informed is obtained, the patient will be enrolled upon admission for transplantation at which moment he/she will be randomised to placebo or azithromycin according to a blinded randomisation-list. In accordance with his/her attributed study-number, each included patient will be assigned to a pre-numbered bottle containing the study-drug, which was pre-filled and blinded for its content and are delivered in advance to the ward by the University Leuven Hospital Pharmacy. From this bottle, a first loading dose of placebo (25 mL po syrup) or azithromycin (25 mL po syrup = 1000 mg) will be given by the nurse during preparation for subsequent lung transplantation (Day 0). After lung transplantation, 'add on' treatment of placebo (6.25 mL) or azithromycin (6.25 mL = 250 mg) syrup will be given via (naso)gastric tube or per os every other day (days 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 and 31) by the nurses taking care of the patient in the early post-transplant period. In case of any serious suspected drug-interactions (however very unlikely) or adverse attributable to the study drug, the study will be promptly stopped in this patient. Serious adverse events will be monitored by the treating lung transplant physicians (blinded for the study-drug) and are defined as allergic reactions including skin reactions (rash, urticaria or Stevens-Johnson syndrome), angioneurotic edema and anaphylaxis, cardiac arrhythmias (ventricular tachycardia or torsades de pointes), neurologic disorders (convulsions). Routine immunosuppressive, prophylactic and necessary antimicrobial treatment according to standardized protocol is given to all patients, independent of study drug. After transplantation, routine follow-up (e.g. biochemical and microbiological blood analyses, chest radiography, pulmonary function testing and bronchoscopic evaluation with broncho-alveolar lavage and/or trans- or endobronchial biopsies will be performed as they are currently routinely being performed as part of the standard, prospective follow-up after lung transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azithromycin | Experimental | Drug: AzithromycinA first dose of azithromycin (25 mL po syrup = 1000 mg) will be given during preparation for subsequent lung transplantation (Day 0). After lung transplantation, 'add on' treatment of azithromycin (6.25 mL = 250 mg) syrup will be given via (naso)gastric tube or per os every other day (days 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 and 31). |
| Ora-Plus | Placebo comparator | Drug: Ora-PlusA first dose of placebo (25 mL po syrup) will be given during preparation for subsequent lung transplantation (Day 0). After lung transplantation, 'add on' treatment of placebo (6.25 mL) syrup will be given via (naso)gastric tube or per os every other day (days 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 and 31). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Signed informed consent
- Adult (age at least 18 years old at moment of transplantation)
- Single lung transplantation, sequential single (double) lung transplantation or heart-lung transplantation
Key exclusion criteria (3 listed)
- Known previous allergy for azithromycin (including skin reactions such as rash, urticaria or Stevens- Johnson syndrome, angioneurotic oedema and anaphylaxis)
- Retransplantation or multi-organ (other than heart-lung) transplantation
- Inclusion in Transmedics® Organ Care System (OCS™ LUNG) study (OCS-LUN-03-2010)(S53795).
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 |
|---|---|---|
| AzithromycinAlso: Zithromax®Zithromax® oral suspension 200 mg/ 5 mL (Pfizer, UK): Zithromax® 1000 mg syrup per os once at recipient intake for lung transplantation (day 0); followed by Zithromax® 250 mg syrup via (naso)gastric tube or per os every other day until one month after lung transplantation (days 1,3,5,7,9,11,13,15, 17,19,21,23,25,27,29 and 31). | Drug | Azithromycin |
| Ora-PlusAlso: Ora-Plus®Ora-Plus® oral suspension (Paddock Laboratories, 3940 Quebec Avenue N, Minneapolis, MN 55427, USA; NDC-number: 0574-0303-16): Ora-Plus® 25mL syrup per os once at recipient intake for lung transplantation (day 0); followed by Ora-Plus® 6.25 mL syrup via (naso)gastric tube or per os every other day until one month after lung transplantation (days 1,3,5,7,9,11,13,15, 17,19,21,23,25,27,29 and 31). | Drug | Ora-Plus |
Primary outcome
Mean forced expiratory volume at one second (FEV1, %pred)
Time frame: at 3 months after lung transplantation
Mean FEV1 (%pred) during the first 3 months after lung transplantation (measured at discharge; thereafter twice weekly until 8 weeks post-transplant and weekly from 8 to 12 weeks post-transplant; i.e. total estimated number of 14 spirometries per patient)
13 secondary outcomes
Length of intubation
Time frame: at 1 month after lung transplantation
Length of Intensive Care Unit (ICU) stay
Time frame: at 3 months after lung transplantation
Length of hospital stay
Time frame: at 3 months after lung transplantation
Partial Pressure of Oxygen in Arterial Blood over fraction of inspired oxygen fraction - ratio (PaO2/FiO2)
Time frame: at 0, 24, 48 and 72 hours after lung transplantation
Primary graft dysfunction (PGD) prevalence and score
Time frame: at 0, 24, 48 and 72 hours after lung transplantation
6-minute walking distance
Time frame: at 1 month after lung transplantation
Acute rejection (grade A; grade B) prevalence/severity
Time frame: at 1, 3 and 6 months after lung transplantation
Broncho-alveolar lavage neutrophilia and cytokine/protein profile
Time frame: at day 1 and at 1, 3 and 6 months after lung transplantation
Airway colonization
Time frame: at day 1 and 1, 3 and 6 months after lung transplantation
Plasma C-reactive protein levels
Time frame: at day 1, 3, 5, 7, 14 and 1, 3 and 6 months after lung transplantation
Mortality
Time frame: at 1, 3 and 6 months after lung transplantation
Ventilator-free days
Time frame: at 6 months after transplantation
Mean forced expiratory volume at one second (FEV1, %pred)
Time frame: at 6 months after lung transplantation
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 11 Nov 2015.
- Derived from this study: PubMed 30686699Van Herck A, Frick AE, Schaevers V, Vranckx A, Verbeken EK, Vanaudenaerde BM, Sacreas A, Heigl T, Neyrinck AP, Van Raemdonck D, Dupont LJ, Yserbyt J, Verleden SE, Verleden GM, Vos R. Azithromycin and early allograft function after lung transplantation: A randomized, controlled trial. J Heart Lung Transplant. 2019 Mar;38(3):252-259. doi: 10.1016/j.healun.2018.12.006. Epub 2018 Dec 14.
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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.
Robin Vos, MD, PhD principal investigator
UZ and KULeuven
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 and Ora-Plus in people with Disorder Related to Lung Transplantation, run by Universitaire Ziekenhuizen 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 3 inclusion and 3 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 11 Nov 2015. 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. 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 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?
Mean forced expiratory volume at one second (FEV1, %pred) (time frame: at 3 months after lung transplantation). 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 NCT01915082, 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 11 Nov 2015.