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A Study Looking at Kidney Function in Kidney Transplant Recipients Who Are Taking Anti-rejection Medication Including Tacrolimus and With or Without Sirolimus. (ADHERE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01363752
Recruitment Status : Completed
First Posted : June 2, 2011
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc

Brief Summary:
The purpose of this study is to compare the effect of two anti-rejection therapy regimens on kidney function in kidney transplant recipients.

Condition or disease Intervention/treatment Phase
Kidney Transplantation Drug: Advagraf Drug: Mycophenolate Mofetil Drug: Sirolimus Drug: Corticosteroids Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 853 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : March 8, 2011
Actual Primary Completion Date : September 18, 2013
Actual Study Completion Date : September 18, 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Advagraf + MMF + Steroids
Without sirolimus
Drug: Advagraf
oral
Other Names:
  • FK506E
  • Prolonged release tacrolimus

Drug: Mycophenolate Mofetil
oral
Other Name: CellCept

Drug: Corticosteroids
i.v. and oral

Experimental: Advagraf + MMF + Steroids + Sirolimus
With sirolimus; MMF withdrawn on Day 28; Sirolimus introduced on Day 28
Drug: Advagraf
oral
Other Names:
  • FK506E
  • Prolonged release tacrolimus

Drug: Mycophenolate Mofetil
oral
Other Name: CellCept

Drug: Sirolimus
oral
Other Name: Rapamune

Drug: Corticosteroids
i.v. and oral




Primary Outcome Measures :
  1. Glomerular Filtration Rate (GFR) estimated by iohexol clearance at Week 52 post kidney transplantation [ Time Frame: up to 1 year ]

Secondary Outcome Measures :
  1. Efficacy failure [ Time Frame: up to 1 year ]
    Composite endpoint defined as graft loss (re-transplantation, nephrectomy, death or dialysis ongoing at the study end) or subject withdrawal

  2. GFR at Week 52 post kidney transplantation by Modification Diet in Renal Disease (MDRD) formula [ Time Frame: up to 1 year ]
  3. GFR at Week 52 post kidney transplantation by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula [ Time Frame: up to 1 year ]
  4. Calculated creatinine clearance at Week 52 post kidney transplantation by Cockcroft and Gault formula [ Time Frame: up to 1 year ]
  5. Incidence of clinical acute rejection [ Time Frame: up to 1 year ]
  6. Time to clinical acute rejection [ Time Frame: up to 1 year ]
  7. Incidence of Biopsy Confirmed Acute Rejection [ Time Frame: up to 1 year ]
  8. Time to Biopsy Confirmed Acute Rejection [ Time Frame: up to 1 year ]
  9. Subject survival [ Time Frame: up to 1 year ]
  10. Graft survival [ Time Frame: up to 1 year ]
  11. New Onset Diabetes Mellitus (NODM) as per American Diabetic Association (ADA) criteria [ Time Frame: up to 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01363752


Locations
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Sponsors and Collaborators
Astellas Pharma Inc
Investigators
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Study Director: Use Central Contact Astellas Pharma Europe Ltd.
Additional Information:
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Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01363752    
Other Study ID Numbers: PMR-EC-1212
2010-019639-37 ( EudraCT Number )
First Posted: June 2, 2011    Key Record Dates
Last Update Posted: July 20, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com/
Keywords provided by Astellas Pharma Inc:
Kidney
Kidney Failure, Acute
Astagraf XL
Immunosuppression
Advagraf
Tacrolimus
Transplant
Additional relevant MeSH terms:
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Mycophenolic Acid
Sirolimus
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents