Non-inferiority Study of Safety and Efficacy of Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in Kidney Transplant Recipients

Novartis

Status and phase: Completed; Phase 3

Conditions: Kidney Transplant

Treatments: Drug: Everolimus and tacrolimus; Drug: mycophenolate mofetil and tacrolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT01025817

CRAD001AUS92

Details and patient eligibility

About

The purpose of this phase 3b study is to compare the safety and efficacy of everolimus with low dose tacrolimus to mycophenolate mofetil with standard dose tacrolimus in kidney transplant recipients.

Enrollment: 613 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female renal recipients 18-70 years of age undergoing kidney transplantation, either primary or re-transplant;
• Recipient of a cadaveric, deceased donor (including expanded criteria donor organs and deceased donor organs after cardiac death), living unrelated or non-HLA identical living related donor kidney;
• Graft must be functional (producing greater than or equal to 100 ml of urine within 24 hours after transplantation) at time of randomization.

Exclusion criteria

• Donor organ with a cold ischemic time > 30 hours;
• Males or females who produce less than 100 ml of urine in the first 24 hours post-transplantation;
• Males or females who are recipients of ABO incompatible transplants, or T cell, or B cell crossmatch positive transplant;
• Males or females with severe total hypercholesterolemia or total hypertriglyceridemia (Patients on lipid lowering treatment with controlled hyperlipidemia are acceptable);
• Males or females who have any surgical or any medical condition, such as severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus, which in the opinion of the investigator, might alter the absorption, distribution, metabolism and/or excretion of study medication.

Other protocol related inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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613 participants in 2 patient groups

Everolimus (EVR) & low dose of tacrolimus

Experimental group

Description:

Everolimus (EVR) and tacrolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.

Treatment:

Drug: Everolimus and tacrolimus

Mycophenolate mofetil & standard dose tacrolimus

Active Comparator group

Description:

Mycophenolate mofetil and tacrolimus (MMF) treatment arm: MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. Tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, target level of tacrolimus was reduced to 5 - 8 ng/mL.

Treatment:

Drug: mycophenolate mofetil and tacrolimus