Kidney TransplantationPhase 4ADHERENCT01363752
A Study Looking at Kidney Function in Kidney Transplant Recipients Who Are Taking Anti-rejection Medication Including Tacrolimus and With or Without Sirolimus.
A Phase 4 study testing Advagraf, Mycophenolate Mofetil and Sirolimus in people with Kidney Transplantation, run by Astellas Pharma Inc at 58 sites in 17 countries.
Trial summary
The purpose of this study is to compare the effect of two anti-rejection therapy regimens on kidney function in kidney transplant recipients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Advagraf, Mycophenolate Mofetil and Sirolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 853 participants
- Where
- 58 sitesin 17 countries
- Study dates
- 8 Mar 2011to 18 Sep 2013
- 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
- End stage kidney disease and a suitable candidate for primary renal transplantation or re-transplantation (unless the graft was lost from rejection within 6 months)
- Receiving a kidney transplant from a deceased or living (non Human Leukocyte Antigen [HLA] identical) donor with compatible ABO blood type
- Female subject of childbearing potential has a negative serum or urine pregnancy test at enrollment
- Female and male subjects agree to maintain highly effective birth control during the study and for 90 days after discontinuation of dosing with study drugs. A highly effective method of birth control is defined as those which result in a low failure rate (CPMP/ ICH/ 286/ 95 modified) of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some Intrauterine Devises (IUDs), sexual abstinence or vasectomized partner
Who cannot join
- Receiving or having previously received an organ transplant other than a kidney
- Cold ischemia time of the donor kidney > 30 hours
- Panel Reactive Antibody (PRA) >20%
- Receiving a graft from a non-heart-beating donor other than of Maastricht category 3 (withdrawal of support awaiting cardiac arrest)
- Significant liver disease, defined as having continuously elevated SGPT/ ALT and/ or SGOT/ AST and/ or total bilirubin levels ≥ 2 times the upper value of the normal range of the investigational site or is receiving a graft from a hepatitis C or B positive donor
- Requiring initial sequential or parallel therapy with immunosuppressive antibody preparation(s)
Show all 14Show fewer
- Requiring ongoing dosing with a systemic immunosuppressive drug prior to transplantation (other than minimal levels of immunosuppression following failure of previous transplantation without nephrectomy)
- Significant, uncontrolled concomitant infections and/ or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer
- Pregnant woman or breast-feeding mother
- Subject or donor known to be HIV positive
- Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids, sirolimus, MMF or any of the product excipients or iodine
- Evidence of malignant disease within the last 5 years, not including non-malignant skin cancers
- Currently participating in another clinical trial, and/ or has taken an investigational drug within 28 days prior to enrollment
- Unlikely to comply with the visits scheduled in the protocol
Trial locations and contacts
58 sites in 17 countries.
58 sites in 17 countries
Germany11 sites
1541
Bochum, 44892
1542
Erlangen, 91054
1543
Essen, 45147
1544
Frankfurt, 60596
1545
Hannoversch Münden, 34346
1540
Hanover, 30625
1546
Heidelberg, 69120
1547
Kiel, 24105
1548
Leipzig, 04103
1549
München, 81377
1550
Münster, 48149
France10 sites
1752
Amiens, 80054
1740
Brest, 29609
1742
Clermont-Ferrand, 63003
1746
Créteil, 94010
1750
Dijon, 21000
1741
Le Kremilin Bicetre Cedex, 94275
1749
Paris, 75743
1751
Toulouse, 31059
1748
Tours, 37044
1745
Vandœuvre-lès-Nancy, 54511
South Korea5 sites
5245
Busan, 614-735
5243
Daegu, 700-721
5242
Seoul, 110-744
5241
Seoul, 120-752
5244
Seoul, 138-736
Russia4 sites
2841
Kemerovo, 650066
2843
Moscow, 115446
2842
Omsk, 644112
2840
Vol'ginskiy, 404120
Spain4 sites
1640
Alicante, 03010
1641
Barcelona, 08907
1643
Santander, 39008
1642
Vizcaya, 48903
Turkey (Türkiye)3 sites
3042
Istanbul, 07058
3043
Istanbul, 34245
3044
Istanbul, 34732
About this study
Official title: A Multicenter, Two Arm, Randomized, Open Label Clinical Study Investigating Renal Function in an Advagraf® Based Immunosuppressive Regimen With or Without Sirolimus in Kidney Transplant Patients
The purpose of this study is to compare the effect of two anti-rejection therapy regimens on kidney function in kidney transplant recipients.
Read the detailed description
This study will evaluate the potential to reduce nephrotoxic calcineurin inhibitors (CNI) therapy by lowering tacrolimus exposure from Advagraf® in combination with the non-nephrotoxic immunosuppressant sirolimus to avoid the risk of acute graft rejection, compared with an Advagraf® and Mycophenolate Mofetil (MMF) immunosuppressive regimen.
- Conditions
- Kidney Transplantation
- Being tested
- Advagraf, Mycophenolate Mofetil, Sirolimus, Corticosteroids
- Keywords
- Kidney, Kidney Failure, Acute, Astagraf XL, Immunosuppression, Advagraf, Tacrolimus, Transplant
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdvagrafDrug
Also called FK506E, Prolonged release tacrolimus
oral
Also called CellCept
oral
SirolimusDrug
Also called Rapamune
oral
CorticosteroidsDrug
i.v. and oral
| Study group | Role | What they receive |
|---|---|---|
| Advagraf + MMF + Steroids | Active comparator | Without sirolimus Receives: Drug: Advagraf; Drug: Mycophenolate Mofetil; Drug: Corticosteroids |
| Advagraf + MMF + Steroids + Sirolimus | Experimental | With sirolimus; MMF withdrawn on Day 28; Sirolimus introduced on Day 28 Receives: Drug: Advagraf; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Drug: Corticosteroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glomerular Filtration Rate (GFR) estimated by iohexol clearance at Week 52 post kidney transplantation
Measured: up to 1 year
Secondary outcomes (11)
Efficacy failure
Composite endpoint defined as graft loss (re-transplantation, nephrectomy, death or dialysis ongoing at the study end) or subject withdrawal
Measured: up to 1 year
GFR at Week 52 post kidney transplantation by Modification Diet in Renal Disease (MDRD) formula
Measured: up to 1 year
GFR at Week 52 post kidney transplantation by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
Measured: up to 1 year
Calculated creatinine clearance at Week 52 post kidney transplantation by Cockcroft and Gault formula
Measured: up to 1 year
Incidence of clinical acute rejection
Measured: up to 1 year
Time to clinical acute rejection
Measured: up to 1 year
Incidence of Biopsy Confirmed Acute Rejection
Measured: up to 1 year
Time to Biopsy Confirmed Acute Rejection
Measured: up to 1 year
Subject survival
Measured: up to 1 year
Graft survival
Measured: up to 1 year
New Onset Diabetes Mellitus (NODM) as per American Diabetic Association (ADA) criteria
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2011 (estimated)
- Study start8 Mar 2011
- Primary completion18 Sep 2013
- Study completion18 Sep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 853 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Use Central Contact, Study director, Astellas Pharma Europe Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01363752
- Sponsor's protocol ID
- PMR-EC-1212
- Other IDs
- 2010-019639-37
- Acronym
- ADHERE
- Status last verified
- Oct 2024
- First submitted
- 31 May 2011
- Last updated
- 31 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Two Arm, Randomized, Open Label Clinical Study Investigating Renal Function in an Advagraf® Based Immunosuppressive Regimen With or Without Sirolimus in Kidney Transplant Patients
- ClinicalTrials.gov ID
- NCT01363752
- Acronym / sponsor ID
- ADHERE / PMR-EC-1212
- Conditions
- Kidney Transplantation
- Keywords
- Kidney, Kidney Failure, Acute, Astagraf XL, Immunosuppression, Advagraf, Tacrolimus, Transplant
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 853 participants (actual)
- Lead sponsor
- Astellas Pharma IncIndustry (pharma, biotech, devices)
- Study start
- 8 Mar 2011 (actual)
- Primary completion
- 18 Sep 2013 (actual)
- Study completion
- 18 Sep 2013 (actual)
- First posted
- 2 Jun 2011 (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.
The purpose of this study is to compare the effect of two anti-rejection therapy regimens on kidney function in kidney transplant recipients.
Detailed description
This study will evaluate the potential to reduce nephrotoxic calcineurin inhibitors (CNI) therapy by lowering tacrolimus exposure from Advagraf® in combination with the non-nephrotoxic immunosuppressant sirolimus to avoid the risk of acute graft rejection, compared with an Advagraf® and Mycophenolate Mofetil (MMF) immunosuppressive regimen.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Advagraf + MMF + Steroids | Active comparator | Drug: Advagraf, Drug: Mycophenolate Mofetil, Drug: CorticosteroidsWithout sirolimus |
| Advagraf + MMF + Steroids + Sirolimus | Experimental | Drug: Advagraf, Drug: Mycophenolate Mofetil, Drug: Sirolimus, Drug: CorticosteroidsWith sirolimus; MMF withdrawn on Day 28; Sirolimus introduced on Day 28 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- End stage kidney disease and a suitable candidate for primary renal transplantation or re-transplantation (unless the graft was lost from rejection within 6 months)
- Receiving a kidney transplant from a deceased or living (non Human Leukocyte Antigen [HLA] identical) donor with compatible ABO blood type
- Female subject of childbearing potential has a negative serum or urine pregnancy test at enrollment
- Female and male subjects agree to maintain highly effective birth control during the study and for 90 days after discontinuation of dosing with study drugs. A highly effective method of birth control is defined as those which result in a low failure rate (CPMP/ ICH/ 286/ 95 modified) of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some Intrauterine Devises (IUDs), sexual abstinence or vasectomized partner
Key exclusion criteria (14 listed)
- Receiving or having previously received an organ transplant other than a kidney
- Cold ischemia time of the donor kidney > 30 hours
- Panel Reactive Antibody (PRA) >20%
- Receiving a graft from a non-heart-beating donor other than of Maastricht category 3 (withdrawal of support awaiting cardiac arrest)
- Significant liver disease, defined as having continuously elevated SGPT/ ALT and/ or SGOT/ AST and/ or total bilirubin levels ≥ 2 times the upper value of the normal range of the investigational site or is receiving a graft from a hepatitis C or B positive donor
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 |
|---|---|---|
| AdvagrafAlso: FK506E, Prolonged release tacrolimusoral | Drug | Advagraf + MMF + Steroids, Advagraf + MMF + Steroids + Sirolimus |
| Mycophenolate MofetilAlso: CellCeptoral | Drug | Advagraf + MMF + Steroids, Advagraf + MMF + Steroids + Sirolimus |
| SirolimusAlso: Rapamuneoral | Drug | Advagraf + MMF + Steroids + Sirolimus |
| Corticosteroidsi.v. and oral | Drug | Advagraf + MMF + Steroids, Advagraf + MMF + Steroids + Sirolimus |
Primary outcome
Glomerular Filtration Rate (GFR) estimated by iohexol clearance at Week 52 post kidney transplantation
Time frame: up to 1 year
11 secondary outcomes
Efficacy failure
Time frame: up to 1 year
GFR at Week 52 post kidney transplantation by Modification Diet in Renal Disease (MDRD) formula
Time frame: up to 1 year
GFR at Week 52 post kidney transplantation by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
Time frame: up to 1 year
Calculated creatinine clearance at Week 52 post kidney transplantation by Cockcroft and Gault formula
Time frame: up to 1 year
Incidence of clinical acute rejection
Time frame: up to 1 year
Time to clinical acute rejection
Time frame: up to 1 year
Incidence of Biopsy Confirmed Acute Rejection
Time frame: up to 1 year
Time to Biopsy Confirmed Acute Rejection
Time frame: up to 1 year
Subject survival
Time frame: up to 1 year
Graft survival
Time frame: up to 1 year
New Onset Diabetes Mellitus (NODM) as per American Diabetic Association (ADA) criteria
Time frame: up to 1 year
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 31 Oct 2024.
- Individual participant dataSharing planned: Yes. Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
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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.
Use Central Contact study director
Astellas Pharma Europe Ltd.
58 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Advagraf, Mycophenolate Mofetil and Sirolimus in people with Kidney Transplantation, run by Astellas Pharma Inc at 58 sites in 17 countries.
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 4 inclusion and 14 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 31 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 58 sites in Germany, France, South Korea, Russia, Spain and 12 more countries. 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. 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?
Glomerular Filtration Rate (GFR) estimated by iohexol clearance at Week 52 post kidney transplantation (time frame: up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Oct 2024.