Comparison of CNI-based Regimen Versus CNI-free Regimen in Kidney Transplant Recipients.

Renal Transplantation Clinical Trial

Official title:

Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a CNI-free Regimen With Enteric-coated Mycophenolate Sodium and Everolimus in Comparison to Standard Therapy With Enteric-coated Mycophenolate Sodium and Ciclosporin Microemulsion in Stable Renal Transplant Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00332839
• Other study ID #: CRAD001ADE02
• Secondary ID: 2005-001013-18
• Status: Terminated
• Phase: Phase 4
• First received: May 31, 2006
• Last updated: August 15, 2014
• Start date: November 2005
• Est. completion date: March 2013

Study information

• Verified date: August 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Calcineurin inhibitors (CNI), a potent immunosuppressive drug used in kidney transplant recipients to prevent graft rejection, may cause renal impairment. The aim of this study is to assess whether a CNI-free regimen with enteric-coated mycophenolate sodium and everolimus is as safe and well tolerated as a standard regimen consisting of enteric-coated mycophenolate sodium and cyclosporine microemulsion without a compromise in therapeutic efficacy while resulting in an improved renal function.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 93
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Males or females, aged > 18 years, Maintenance renal transplant recipients at least 6 months post-transplantation, Patients with a serum creatinine < 2,5 mg/dL stable for at least three month (according to the investigator), Females capable of becoming pregnant had to have a negative serum pregnancy test within seven days prior to or at baseline, and were required to practice an approved method of birth control for the duration of the study and for a period of six weeks following discontinuation of study medication, even where there had been a history of infertility, Patients receiving Myfortic® (Myfortic dose . 720 mg/d) and Sandimmun® Optoral with or without corticosteroids as part of their immunosuppressive regimen for at least 1 month before baseline;

Exclusion Criteria:

More than one previous renal transplantation, Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney, Patient with proteinuria > 1000 mg/day at baseline, Hypersensitivity to Certican®, Sandimmun® Optoral, Prograf®, mycophenolic acid, or other components of the formulation, Patients who had received an investigational drug within four weeks prior to baseline, Severe rejection (= Banff II acute rejection), recurrent acute rejection, or steroid resistant rejection within six months of enrollment, Thrombocytopenia (platelets < 100,000/mm³), with an absolute neutrophil count of < 1,500/mm³ or leukopenia (leukocytes < 4,000/mm³), or hemoglobin < 8 g/dL, Abnormal physical or laboratory findings of clinical significance within two weeks of study inclusion which at the investigator's discretion would interfere with the objectives of the study, Symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator, or patients who were unlikely to comply with the study requirements, or who were unable to give informed consent, History of malignancy during the last five years, except squamous or basal cell carcinoma of the skin, Patients who were HIV positive, or hepatitis C, or hepatitis B surface antigen positiveEvidence of severe liver disease (including abnormal liver enzyme profile, i.e. aspartate transaminase (AST), alanine aminotransferase (ALT) or total bilirubin > 3 times upper limit of normal (ULN), Females of childbearing potential who were planning to become pregnant, who were pregnant or lactating and/or who were unwilling to use effective means of contraception, Presence of a clinically significant infection requiring continued therapy, severe diarrhea, active peptic ulcer disease or uncontrolled diabetes mellitus that in the opinion of the investigator would interfere with the appropriate conduct of the study, Evidence of drug or alcohol abuse

Other protocol-defined exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Drug:
• Everolimus
Participants, switching from the CsA based treatment, initially received everolimus 1.5 mg/day and then from day 7, 3 mg/day, and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml). Participants, switching from the tacrolimus based treatment, initially received 3 mg/day and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml).
• Cyclosporin A (CsA)
The dose was based on the participants' blood level of C0h (80-150 ng/ml).
• Tacrolimus
The dose was based on the participants' blood level of C0h (5-10 ng/ml).
• Enteric Coated - Mycophenolate Sodium (EC-MPS)
The dose was = 720 mg/day.
• Corticosteroids
Corticosteroids were given according to local standard and/or the Investigators' discretion.

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Heilbronn
Germany	Novartis Investigative Site	Kaiserslautern
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Muenster

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal Function	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.	12 months	No
Secondary	Biopsy Proven Acute Rejection, Graft Loss, and Death	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.	12 months	No
Secondary	Occurrence of Treatment Failures	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.	12 months	No
Secondary	Evolution of Renal Function	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.	Baseline, 12 months	No
Secondary	Number of Participants Who Experienced Adverse Events and Death	Participants were monitored for adverse events, serious adverse events and deaths thorughout the prospective and follow-up phases of the study.	12 months	Yes
Secondary	Changes in Cardiovascular Risk	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.	Baseline, 12 months	Yes
Secondary	Changes in Proteinuria	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.	Baseline, 12 months	Yes