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Trial registered on ANZCTR


Registration number
ACTRN12618001394235
Ethics application status
Approved
Date submitted
13/08/2018
Date registered
20/08/2018
Date last updated
11/02/2021
Date data sharing statement initially provided
23/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Immunoglobulin therapy in Lung Transplant
Scientific title
A Randomised Double-blind Placebo-controlled Pilot Study of Intravenous Immunoglobulin Replacement therapy in Lung Transplantation
Secondary ID [1] 295790 0
Nil known
Universal Trial Number (UTN)
U1111-1218-9060
Trial acronym
Linked study record
Not applicable

Health condition
Health condition(s) or problem(s) studied:
Transplantation 309222 0
Condition category
Condition code
Respiratory 308096 308096 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intravenous Human Immunoglobulin 0.4g/kg at 6 weeks post transplant and then monthly x 6 infusions
The infusions will be administered at The Alfred Hospital as per standard clinical practice, supervised by unblinded study coordinators.
Intervention code [1] 312122 0
Treatment: Drugs
Comparator / control treatment
Intravenous human albumin of equivalent volume as if in interventional arm monthly x 6 infusions
Control group
Placebo

Outcomes
Primary outcome [1] 307075 0
Composite analysis of the proportion of patients
• Screened that are eligible
• Eligible that are enrolled
• Lost to follow-up or withdraw from the trial
• Receive their allocated treatment throughout their trial participation
• Missing data during trial data collection
Timepoint [1] 307075 0
12 months post transplant
Secondary outcome [1] 350564 0
• Composite of i) death with a failing graft, ii) re-transplantation and iii) CLAD as determined
from medical notes
Timepoint [1] 350564 0
12 months post transplant
Secondary outcome [2] 350623 0
All-cause mortality rates
Timepoint [2] 350623 0
12 months post transplant
Secondary outcome [3] 350624 0
Incidence of acute cellular rejection determined by endobronchial biopsy or clinical judgement during the first year post transplant
Timepoint [3] 350624 0
12 months post transplant
Secondary outcome [4] 350625 0
Incidence of antibody-mediated rejection as determined by clinical judgement during the first year after transplant
Timepoint [4] 350625 0
12 months post transplant
Secondary outcome [5] 350626 0
De novo production of anti-HLA donor specific antibodies by Luminex as per standard of care
Timepoint [5] 350626 0
3 months post transplant and 12 months post transplant
Secondary outcome [6] 350627 0
Hospital admissions for treatment of infections during the first year post transplant.
Collected from medical records of the treating hospital, with participant consent
Timepoint [6] 350627 0
12 months post transplant
Secondary outcome [7] 350628 0
CMV reactivation in the lung allograft, CMV viremia and CMV end-organ disease in the first year after transplant.
Collected from medical records of the treating hospital, with participant consent
Timepoint [7] 350628 0
12 months post transplant
Secondary outcome [8] 350629 0
Incidence of hypogammaglobulinemia (IgG < 6.5 g/dL) tested monthly while receiving trial infusions
This will be tested at The Alfred Hospital by serum assay and stored in the hospital pathology database under specific trial identification. The result will be provided to the unblended study coordinator and reviewed by a transplant consultant not listed as an investigator in order to determine whether the result is significant
Timepoint [8] 350629 0
12 months post transplant
Secondary outcome [9] 350630 0
IVIg-related adverse events
Any adverse event occurring at the time of infusion will be observed and described by the study coordinator in attendance during the infusion. Any other event potentially related to the infusion will be discussed with the participant and the principle investigator
Generally, IVIg infusions are well tolerated and the most frequent adverse events that include headache, fever and nausea occur in less than 5% of patients. Anaphylaxis is extremely rare.
Timepoint [9] 350630 0
Throughout 6 months of trial infusions
Secondary outcome [10] 350631 0
Proportion of patients who discontinue IVIg because of an adverse drug reaction
This data will be collected from medical records.
Timepoint [10] 350631 0
12 months post Transplant
Secondary outcome [11] 350632 0
Composite analysis of immune cells and biomarkers of infection and rejection in bronchoalveolar fluid and blood by extensive profiling of the immune system (T cells, B cells, NK cells and complement system)
Timepoint [11] 350632 0
At 6 weeks, and 3,6,9,12 months post transplant

Eligibility
Key inclusion criteria
• Male and female aged greater than or equal to 18 years
• Undergoing single lung transplant, bilateral sequential lung transplant (BSLT) or heart-lung transplant (HLT)
• Able to give written informed consent
• Able to understand and comply with all trial requirements
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Known allergy to IVIg
• Active treatment for acute cellular or antibody mediated rejection
• Known history of severe selective IgA deficiency (<5mg/dL)
• Patients who have received IVIg pre- or post –transplant for any medical indication
• History of non-provoked thrombotic events in preceding 3 months
• LTx recipients who are not followed up long-term at Alfred Health
• Re-transplant
• Hospitalisation requiring intubation or mechanical ventilation at the time of enrolment.
• Any other severe condition which in the investigator’s judgment may interfere with the trial evaluations or severely compromise patient safety
• Currently involved in another investigational interventional trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A computerised schedule will be generated prior to trial commencement. The randomisation schedule will be used to prepare opaque sealed envelopes containing the unique patient identification number and the group to which they are assigned.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be stratified according to the presence of significant hypogammaglobulinemia (<5g/dL) measured pre-transplant, in the absence of IVIg replacement. Each of these groups will be further stratified according to pre-LTx sensitisation status, as defined by the most recent pre-transplant presence of anti-HLA donor specific antibodies. Patients will fall into 1 of 4 groups. A computerised randomisation schedule will be independently generated for each group.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The statistical analyses will be mainly descriptive using an intention-to-treat framework including all eligible randomized patients.
As the end-point of time to develop of a composite of i) death with a failing graft, ii) re-transplantation and iii) CLAD (censored at the end of follow-up) forms the basis of the sample size calculation for a future definitive efficacy RCT comparisons between both arms will be made using Cox proportional hazards model with treatment allocation as the only dependent variable.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/09/2018
Actual
4/02/2019
Date of last participant enrolment
Anticipated
1/12/2021
Actual
Date of last data collection
Anticipated
1/12/2022
Actual
Sample size
Target
40
Accrual to date
18
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11643 0
The Alfred - Prahran
Recruitment postcode(s) [1] 23690 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 300383 0
Commercial sector/Industry
Name [1] 300383 0
CSL Behring
Country [1] 300383 0
United States of America
Primary sponsor type
Hospital
Name
The Alfred Hospital
Address
55 Commercial Road, Prahran, VIC 3181
Country
Australia
Secondary sponsor category [1] 299836 0
None
Name [1] 299836 0
Address [1] 299836 0
Country [1] 299836 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301192 0
Alfred Hospital Ethics committee
Ethics committee address [1] 301192 0
Ethics committee country [1] 301192 0
Australia
Date submitted for ethics approval [1] 301192 0
22/01/2018
Approval date [1] 301192 0
09/05/2018
Ethics approval number [1] 301192 0
53/18

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86170 0
A/Prof Glen Westall
Address 86170 0
Department of Respiratory Medicine
The Alfred Hospital
Commercial Road,
Prahran, VIC 3181
Country 86170 0
Australia
Phone 86170 0
+61 3 9076 2405
Fax 86170 0
+61 3 90765701
Email 86170 0
g.westall@alfred.org.au
Contact person for public queries
Name 86171 0
Glen Westall
Address 86171 0
Department of Respiratory Medicine
The Alfred Hospital
Commercial Road,
Prahran, VIC 3181
Country 86171 0
Australia
Phone 86171 0
+61 3 9076 2405
Fax 86171 0
+61 3 90765701
Email 86171 0
g.westall@alfred.org.au
Contact person for scientific queries
Name 86172 0
Glen Westall
Address 86172 0
Department of Respiratory Medicine
The Alfred Hospital
Commercial Road,
Prahran, VIC 3181
Country 86172 0
Australia
Phone 86172 0
+61 3 9076 2405
Fax 86172 0
+61 3 90765701
Email 86172 0
g.westall@alfred.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Only group data will be submitted for publication


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.