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Trial registered on ANZCTR


Registration number
ACTRN12611000316909
Ethics application status
Not yet submitted
Date submitted
24/03/2011
Date registered
24/03/2011
Date last updated
24/03/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of proton pump inhibitor on mycophenolic acid absorption in kidney and liver transplant recipients
Scientific title
A prospective, double-blind placebo-controlled multicentre trial to assess mycophenolic acid area under curve following Mycophenolate Mofetil and Enteric-coated Mycophenolic Acid in the presence and absence of the proton-pump inhibitor Pantoprazole in kidney and liver transplant recipients
Secondary ID [1] 259847 0
Nil
Universal Trial Number (UTN)
Trial acronym
Interaction of the Proton Pump Inhibitor (PPI) Pantoprazole on MycoPhenolic ACid (MPA) exposure In Kidney And Liver Transplant Recipients (IMPACT Study)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Drug interaction 265420 0
Condition category
Condition code
Renal and Urogenital 265593 265593 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pantoprazole 40mg oral tablet once daily for 7 days. There will be a 1-week washout period between treatments.
Intervention code [1] 264266 0
Treatment: Drugs
Comparator / control treatment
Placebo (identical in taste and appearance with no active ingredient) 1 tablet once daily for 7 days. There will be a 1-week washout period between treatments.
Control group
Placebo

Outcomes
Primary outcome [1] 262380 0
Dose normalised area under the curve (AUC) for mycophenolic acid (MPA) and MPA-ether glucuronide (MPA-Ge) will be determined using validated assay
Timepoint [1] 262380 0
Days 7 and 21
Secondary outcome [1] 273658 0
Transplant graft outcomes (clinical assessments, blood and urine test)
Timepoint [1] 273658 0
Days 7 and 21
Secondary outcome [2] 273659 0
Plasma calcineurin-inhibitor levels (blood test)
Timepoint [2] 273659 0
Days 7 and 21
Secondary outcome [3] 273660 0
Plasma pantoprazole levels (blood test)
Timepoint [3] 273660 0
Days 7 and 21

Eligibility
Key inclusion criteria
Inclusion Criteria:
1. Males and females >18 years.
2. Kidney and liver transplant recipients of deceased-donor organs or for renal only, living donor organs. Recipients must be at least 6 months post-transplant.
3. Recipients who are willing to change to pantoprazole (from other proton-pump inhibitor or H2-antagonist) or willing to start pantoprazole if not already on this drug.
4. Maintained on either cyclosporine or tacrolimus.
5. Capable of giving written informed consent and adhering to the study schedule.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria:
1. Recipients who are unwilling to change to pantoprazole (from other proton-pump inhibitor or H2-antagonist) or unwilling to start pantoprazole if not already on this.
2. Patients maintained on everolimus, sirolimus or other non-calcineurin inhibitor except corticosteroids.
3. Recent change (<2 weeks) in dose of mycophenolate mofetil or enteric coated-mycophenolic sodium (EC-MPS).
4. Recent substantial change (>50% change in dosage within 2 weeks prior to inclusion) in dose of calcineurin-inhibitor (CNI).
5. Recent acute rejection requiring methylprednisolone within 1 month prior to inclusion.
6. Change in dose of corticosteroids (prednisolone) within 2 weeks prior to inclusion.
7. MDRD derived estimated glomerular filtration rate (eGFR) <30mL/min or alanine amino-transaminase (ALT) >3x upper limit of normal (ULN) or aspartate amino-transferase (AST) >3xULN or bilirubin >2xULN.
8. Plan change in dosing of MMF or EC-MPS or CNI during study period.
9. Significant peptic ulcer disease or ulcerative oesophagitis where withdrawal of current acid suppression therapy is not clinically appropriate.
10. Concurrent use of magnesium and aluminium antacid or cholestyramine.

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)
The authorized person(s) and/or research staff will receive a set of treatment allocation cards (separate cards for kidney and liver transplant recipients) with sequential randomization numbers on which the treatment group information is covered by a label or sealed within an envelope. Each number will correspond to 2 packets of study medications clearly labelled as ‘Packet 1’ or ‘Packet 2’.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by coin-tossing
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 3872 0
6009

Funding & Sponsors
Funding source category [1] 264723 0
Commercial sector/Industry
Name [1] 264723 0
Novartis Pharmaceuticals Australia Pty Limited
Address [1] 264723 0
54 Waterloo Road
North Ryde NSW 2113
Country [1] 264723 0
Australia
Primary sponsor type
Government body
Name
Health Department of Western Australia
Address
Department of Health
189 Royal Street
East Perth WA 6004
Country
Australia
Secondary sponsor category [1] 263849 0
None
Name [1] 263849 0
Address [1] 263849 0
Country [1] 263849 0
Other collaborator category [1] 251895 0
Government body
Name [1] 251895 0
Royal Adelaide Hospital
Address [1] 251895 0
PO Box 287
Rundle Mall
South Australia 5000
Country [1] 251895 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 266710 0
Sir Charles Gairdner Hospital Group
Ethics committee address [1] 266710 0
Hospital Avenue,
NEDLANDS WA 6009
Ethics committee country [1] 266710 0
Australia
Date submitted for ethics approval [1] 266710 0
01/02/2011
Approval date [1] 266710 0
Ethics approval number [1] 266710 0
2011-004
Ethics committee name [2] 266711 0
Royal Adelaide Hospital
Ethics committee address [2] 266711 0
PO Box 287
Rundle Mall
South Australia 5000
Ethics committee country [2] 266711 0
Australia
Date submitted for ethics approval [2] 266711 0
23/03/2011
Approval date [2] 266711 0
Ethics approval number [2] 266711 0

Summary
Brief summary
To determine the effect of gastric acid suppression (using the proton pump inhibitor [PPI] pantoprazole) on the pharmacokinetics of mycophenolic acid (MPA) in kidney and liver transplant recipients maintained on either mycophenolate mofetil [MMF] or enteric-coated mycophenolate sodium [EC-MPS]. The following outcomes will be assessed:
a. MPA area under curve (AUC).
b. Clinical outcomes including rejection, graft function and proteinuria.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32377 0
Address 32377 0
Country 32377 0
Phone 32377 0
Fax 32377 0
Email 32377 0
Contact person for public queries
Name 15624 0
Dr Wai Lim
Address 15624 0
Department of Renal Medicine
Sir Charles Gairdner Hospital
Hospital Avenue,
NEDLANDS WA 6009
Country 15624 0
Australia
Phone 15624 0
+61 8 93462799
Fax 15624 0
+61 8 93463942
Email 15624 0
wai.lim@health.wa.gov.au
Contact person for scientific queries
Name 6552 0
Dr Wai Lim
Address 6552 0
Department of Renal Medicine
Sir Charles Gairdner Hospital
Hospital Avenue,
NEDLANDS WA 6009
Country 6552 0
Australia
Phone 6552 0
+61 8 93462799
Fax 6552 0
+61 8 93463942
Email 6552 0
wai.lim@health.wa.gov.au

No information has been provided regarding IPD availability
Summary results
No Results