Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000551897
Ethics application status
Approved
Date submitted
7/05/2012
Date registered
24/05/2012
Date last updated
18/12/2018
Date data sharing statement initially provided
18/12/2018
Date results information initially provided
18/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Measuring cytomegalovirus (CMV) immunity to direct optimal length of CMV prophylaxis following lung transplantation.
Scientific title
In lung transplant recipients at risk of cytomegalovirus reactivation how does QuantiFERON-CMV directed cytomegalovirus prophylaxis compare to standard of care cytomegalovirus prophylaxis to reduce the incidence of late onset cytomegalovirus infection.
Secondary ID [1] 280445 0
Nil
Universal Trial Number (UTN)
U1111-1129-8079
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Transplantation 286418 0
Cytomegalovirus 286419 0
Condition category
Condition code
Respiratory 286670 286670 0 0
Other respiratory disorders / diseases
Infection 286781 286781 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention involves directing patient care according to the results of the patients QuantiFERON-CMV blood test. At 5 months post lung transplant patients will be randomised to receive (1) standard of care - cessation of antiviral prophylaxis at 5 months post-transplant, or (2) QuantiFERON-CMV directed care - where patients prophylaxis will be individualised according to their blood results, with their first QFN-CMV assay being taken at their 5 month visit. If the QFN-CMV assay is positive, the patients will cease antiviral prophylaxis, if the QFN-CMV assay is negative, the patients will receive a further 3 months antiviral prophylaxis (valganciclovir 450mg tablet orally twice daily). The QFN-CMV assay will be repeated at 8 months post-transplant, if positive, cease antiviral prophylaxis, if negative continue a further 3 months antiviral prophylaxis (valganciclovir 450mg tablet orally twice daily). The QFN-CMV assay will be repeated for a final time at 11 months post transplant, and regardless of results, the patient will cease antiviral prophylaxis.
Intervention code [1] 284803 0
Prevention
Comparator / control treatment
Standard Treatment – cessation of antiviral prophylaxis (valganciclovir 450mg twice daily) at 5 months post-transplant.
Control group
Active

Outcomes
Primary outcome [1] 287073 0
The effectiveness of QuantiFERON-CMV directed antiviral prophylaxis on the incidence of CMV reactivation within the lung allograft in patients at-risk of CMV reactivation. CMV reactivation within the lung allograft will be assessed as the presence of CMV in the BAL, deifined as greater than or equal to 600 copies.
Timepoint [1] 287073 0
Within 18 months of transplant
Secondary outcome [1] 297317 0
Compare the need for intravenous ganciclovir in both arms of the study. The need for intravenous ganciclovir will be assessed by the presciption for, the incidence of use and the duration of treatment in all study participants.
Timepoint [1] 297317 0
Within 18 months of transplant
Secondary outcome [2] 297319 0
Evaluate the incidence of ganciclovir resistance in all study patients. The incidence of ganciclovir resistance will be based on the clinical evaulation by the treating physician and documented in the source documents. The incidence of patients with ganciclovir resistence documented will be collected in all participants.
Timepoint [2] 297319 0
Within 18 months of tranpslant
Secondary outcome [3] 297321 0
Evaluate the presence of CMV-specific immunity. QFN-CMV assay will be tested on all study patients at 5, 8 & 11 months post transplant. The QFN-CMV assay will identify the presence of CMV-specific immunity in all study participants will enable this outcome to be assessed.
Timepoint [3] 297321 0
At 5, 8 and 11 months post tranpslant
Secondary outcome [4] 297322 0
Evaluate the incidence of acute cellular rejection. Acute cellular rejection will be defined by as a Lung Biopsy Grade greater than or equal to A1 (as defined by ISHLT). Lung biospy and assessment for acute cellular rejection occur routinely in the first 18 months of tranpslant, and the incidence of this will be collected in all patients.
Timepoint [4] 297322 0
Within 18 months of tranpslant
Secondary outcome [5] 297323 0
Assess frequency of side effects from antiviral therapy. Some of the known side effects to valganciclovir include diarrhoea, nausea, fevers, headaches, fatigue, hypertension, infection, neutropaenia, anaemia, decreased fertility, tremor, and there may be other less common or unreproted possible side effects. All participants will have their source notes reviewed for the above side effects, and these will be recorded in the adverse event log of the case report forms for evaulation.
Timepoint [5] 297323 0
Within 18 months of transplant
Secondary outcome [6] 297324 0
Evaluate survival.
Timepoint [6] 297324 0
Within 18 months of tranpslant
Secondary outcome [7] 297325 0
Evaluate the incidence of BOS. BOS is a physiological assessment of lung function as measured by spirometry, as defined by ISHLT. BOS is present if there is 20% drop in lung fuction compared to the best lung function achieved following lung transoplantation, in the absence of other reversible causes.
Timepoint [7] 297325 0
Within 18 months of transplant

Eligibility
Key inclusion criteria
Adult (greater than or equal to 18yrs) lung transplant recipients, who are at risk of CMV reactivation, and who have provided written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) CMV seronegative recipient and seronegative donor, (2) known ganciclovir resistance, (3) valganciclovir-related neutropenia, (4) BOS grad 3 or BOS with unstable FEV1, (5) hospitalized requiring intubation or mechanical ventilation, (6) active treatment for acute graft rejection, (7) pregnant, lactating, or breast feeding, (8) known hypersensitivity to valganciclovir, or (9) any other condition in the investigators medical opinion that precludes the patients participation.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/06/2012
Actual
20/06/2012
Date of last participant enrolment
Anticipated
Actual
18/03/2016
Date of last data collection
Anticipated
Actual
30/04/2017
Sample size
Target
210
Accrual to date
Final
119
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 285206 0
Hospital
Name [1] 285206 0
The Alfred Hospital
Country [1] 285206 0
Australia
Primary sponsor type
Hospital
Name
Dr Glenn Westall, for The Alfred Hospital
Address
Department AIRMed,
5th Floor, Alfred Hospital
Commercial Road
Melbourne
Victoria 3004
Country
Australia
Secondary sponsor category [1] 284078 0
None
Name [1] 284078 0
Address [1] 284078 0
Country [1] 284078 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287209 0
The Alfred Hospital Ethic Committee
Ethics committee address [1] 287209 0
Dept of Ethics and Research
The Alfred Hospital
Commercial Road
Melbourne
Victoria 3004
Ethics committee country [1] 287209 0
Australia
Date submitted for ethics approval [1] 287209 0
Approval date [1] 287209 0
03/05/2012
Ethics approval number [1] 287209 0
83-12

Summary
Brief summary
After lung transplantation, all patients receive medications, called immunosuppressives. These drugs suppress the immune system and prevent the body from rejecting the transplanted lung(s), but this also makes them susceptible to infections. CMV is a virus known to cause infection after transplantation and affects over 40% of patients and may influence the on-going success of their new lung(s). To reduce the damage that CMV can cause in newly transplanted lungs, all patients undergoing lung transplantation take medications, called anti-virals (Valganciclovir), for approximately the first five months following the transplant operation. Valganciclovir is approved in Australia for use to reduce CMV infection after lung transplantation. However, CMV infection can occur after the anti-viral drugs are stopped. The purpose of this project is to see whether a blood test (QuantiFERON-CMV assay) that assesses whether you can mount an immune response against CMV, can predict which patients are at risk of ongoing CMV infection, and therefore would benefit from taking the anti-viral medication (Valganciclovir) for a longer period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34142 0
A/Prof Glen Westall
Address 34142 0
The Alfred Hospital, Dept of AIRMed, Commercial Road, Melbourne, VICTORIA, 3004
Country 34142 0
Australia
Phone 34142 0
+ 61 3 9076 2000
Fax 34142 0
+ 61 3 9076 8225
Email 34142 0
g.westall@alfred.org.au
Contact person for public queries
Name 17389 0
A/Prof Dr Glen Westall
Address 17389 0
The Alfred Hospital
Dept of AIRMed
Commercial Road
Melbourne
Victoria 3004
Country 17389 0
Australia
Phone 17389 0
+61 3 9076 2000
Fax 17389 0
Email 17389 0
g.westall@alfred.org.au
Contact person for scientific queries
Name 8317 0
A/Prof Dr Glen Westall
Address 8317 0
The Alfred Hospital
Dept of AIRMed
Commercial Road
Melbourne
Victoria 3004
Country 8317 0
Australia
Phone 8317 0
+61 3 9076 2000
Fax 8317 0
Email 8317 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
IPD sharing is not approved under the current Ethics Approval.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Transplantation: September 21, 2018 - Volume Onlin... [More Details]
Plain language summaryNo Using the QFN-CMV blood test to dictate the length... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA Randomized Study of Quantiferon CMV-directed Versus Fixed-duration Valganciclovir Prophylaxis to Reduce Late CMV after Lung Transplantation.2019https://dx.doi.org/10.1097/TP.0000000000002454
N.B. These documents automatically identified may not have been verified by the study sponsor.