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REnal Function in Liver Transplantation: Everolimus With Calcineurin Inhibitor (CNI)-Sparing sTrategy (REFLECT)

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ClinicalTrials.gov Identifier: NCT02115113
Recruitment Status : Recruiting
First Posted : April 15, 2014
Last Update Posted : September 28, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is, starting from the Italian clinical practice in liver transplantation, to optimize the immunosuppressive therapy, considering specific patient characteristics as alcoholic cirrhosis, hepatitis C virus (HCV), hepatocellular carcinoma (HCC), and short/long-term implications. Then efficacy and safety of a calcineurin inhibitor (CNI)-withdrawal regimen will be evaluated in comparison with a CNI-minimization regimen.

Condition or disease Intervention/treatment Phase
Liver Transplantation Drug: Everolimus Drug: Tacrolimus Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 415 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Prospective, Open-label, Controlled, Randomized, Parallel Groups Study to Evaluate the Renal Function of Adult Liver Transplant Recipients Treated With Two Everolimus-based Immunosuppressive Regimens (Tacrolimus Withdrawal vs. Minimization) Until 12 Months Post-transplant, With a 6-months Follow-up
Study Start Date : March 2014
Estimated Primary Completion Date : August 2017
Estimated Study Completion Date : August 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A (Tacrolimus Elimination Arm) Drug: Everolimus

Commercial product labeled according to local requirements will be provided as 0.25 mg and 0.75 mg tablets for oral administration.

At 5 months after transplant, doses will be adjusted to achieve C-0h blood trough level target ranges 6-10 ng/mL.

Tacrolimus withdrawal should be completed by 6 months after transplant.


Active Comparator: Group B (Tacrolimus Minimization Arm) Drug: Everolimus
Commercial product labeled according to local requirements will be provided as 0.25 mg and 0.75 mg tablets for oral administration. At 5 months after transplant, doses will continue to be adjusted to achieve C-0h blood trough level target ranges 3-8 ng/mL.

Drug: Tacrolimus
Commercial product labeled according to local requirements will be provided as 0.5 mg, 1.0 mg and 5.0 mg capsules for oral administration. At 5 months after transplant, doses will continue to be adjusted to achieve C-0h blood trough level target ranges 3-5 ng/mL.




Primary Outcome Measures :
  1. Renal function assessed by estimated glomerular filtartion rate (eGFR) using the MDRD-4 formula (Modification of Diet in Renal Disease, 4 variables) [ Time Frame: At 12 months post-transplant ]

Secondary Outcome Measures :
  1. Composite efficacy failure rate of treated biopsy proven acute rejection (tBPAR), Graft Loss (GL) or Death (D) [ Time Frame: At 12 months post-transplant ]


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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 at Baseline:

  • Male and female liver transplant recipients who are ≥ 18 years of age, treated with a tacrolimus-based immunosuppressive regimen, who have received an induction therapy or i.v. steroids as per local clinical practice.
  • Recipients of a full-size or technically modified liver allograft will be eligible at 4 weeks (± 7 days) after liver transplantation.
  • Allograft is functioning at an acceptable level by the time of Baseline as defined by the AST, ALT, total bilirubin levels ≤ 3 times ULN and INR < 1.5 times ULN.
  • Abbreviated MDRD-4 eGFR ≥ 30 mL/min/1.73m2. Serum creatinine results obtained within 5 days prior to Baseline are acceptable.

Inclusion criteria at Randomization:

  • Effective tacrolimus minimization, confirmed by stable blood trough levels in the two months prior to randomization, i.e. verification of last two tacrolimus blood trough level ≤ 5 ng/mL in the two months prior to randomization. Investigators should make adjustments in tacrolimus dosing to continue to target trough levels ≤ 5 ng/mL prior to randomization.
  • Abbreviated MDRD-4 eGFR ≥ 30 mL/min/1.73m2. Serum creatinine results obtained within 5 days prior to Visit 5 are acceptable.

Exclusion criteria at Baseline:

  • Patients who are recipients of multiple solid organ transplants, (e.g., multivisceral or combined liver-kidney transplants), or have previously received an organ or tissue transplanted, or who received an AB0 incompatible transplant.
  • Patients who experienced more than one episode of treated biopsy proven acute rejection (BANFF ≥ 3 or RAI ≥ 7) or one steroid-resistant acute rejection.
  • Patients who require renal replacement therapy.
  • Patients with a confirmed spot urine protein/creatinine ratio that indicates ≥1.0 g/24 hrs of proteinuria.
  • History of malignancy of any organ system within the past 5 years whether or not there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin or HCC.

Exclusion criteria at Randomization:

  • Patients who experienced more than two episodes of treated biopsy proven acute rejection (BANFF ≥ 3 or RAI ≥ 7) since transplantation or one steroid-resistant acute rejection during the run-in period.
  • Patients with a confirmed spot urine protein/creatinine ratio that indicates ≥ 3.0 g/24 hrs of proteinuria.

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): NCT02115113


Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
Italy
Novartis Investigative Site Recruiting
Ancona, AN, Italy, 60126
Novartis Investigative Site Recruiting
Bari, BA, Italy, 70124
Novartis Investigative Site Recruiting
Bergamo, BG, Italy, 24128
Novartis Investigative Site Recruiting
Bologna, BO, Italy, 40138
Novartis Investigative Site Recruiting
Cagliari, CA, Italy, 09134
Novartis Investigative Site Withdrawn
Cagliari, CA, Italy, 09134
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20122
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20162
Novartis Investigative Site Recruiting
Modena, MO, Italy, 41100
Novartis Investigative Site Recruiting
Padova, PD, Italy, 35128
Novartis Investigative Site Recruiting
Pisa, PI, Italy, 56124
Novartis Investigative Site Recruiting
Roma, RM, Italy, 00144
Novartis Investigative Site Recruiting
Roma, RM, Italy, 00152
Novartis Investigative Site Not yet recruiting
Roma, RM, Italy, 00161
Novartis Investigative Site Recruiting
Roma, RM, Italy, 00168
Novartis Investigative Site Recruiting
Torino, TO, Italy, 10126
Novartis Investigative Site Recruiting
Udine, UD, Italy, 33100
Novartis Investigative Site Recruiting
Verona, VR, Italy, 37126
Novartis Investigative Site Recruiting
Napoli, Italy, 80132
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02115113     History of Changes
Other Study ID Numbers: CRAD001HIT34
2013-004325-91 ( EudraCT Number )
First Posted: April 15, 2014    Key Record Dates
Last Update Posted: September 28, 2016
Last Verified: September 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Liver transplantation, everolimus, CNI-minimization, CNI-elimination, renal function

Additional relevant MeSH terms:
Tacrolimus
Everolimus
Sirolimus
Calcineurin Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents