Non-inferiority Study of Safety and Efficacy of Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in Kidney Transplant Recipients
|ClinicalTrials.gov Identifier: NCT01025817|
Recruitment Status : Completed
First Posted : December 4, 2009
Results First Posted : June 6, 2014
Last Update Posted : November 11, 2015
|Condition or disease||Intervention/treatment||Phase|
|Kidney Transplant||Drug: Everolimus and tacrolimus Drug: mycophenolate mofetil and tacrolimus||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||613 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A 12 Month, Multi-center, Randomized, Open-label Non-inferiority Study Comparing Safety and Efficacy of Concentration-controlled Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in de Novo Renal Transplant Recipients|
|Study Start Date :||January 2010|
|Actual Primary Completion Date :||March 2013|
|Actual Study Completion Date :||March 2013|
Experimental: Everolimus (EVR) & low dose of tacrolimus
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.
Drug: Everolimus and tacrolimus
Active Comparator: Mycophenolate mofetil & standard dose tacrolimus
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.
Drug: mycophenolate mofetil and tacrolimus
Mycophenolate mofetil: - Dose form: 250 mg capsule - Dose: 2g per day - Frequency: 1g twice daily Tacrolimus: - Dose adjusted to maintain specific blood levels
Other Name: Active Comparator Control)
- Number of Participants With Incidence of Composite Efficacy Failure [ Time Frame: 12 Months ]Efficacy failure rate used the composite endpoint of: (1) treated biopsy-proven acute rejection (BPAR)*, (2) graft loss**, (3) participant death or(4) loss to follow-up. *A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. **Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis.
- Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: 12 Months ]Renal function was assessed by estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. MDRD formula: GFR [mL/min/1.73m˄2] = 186.3*(C˄-1.154)*(A˄-0.203)*G*R. DEFINITIONS: C = serum concentration of creatinine [mg/dL]; A = age [years]; G = 0.742 when gender is female, otherwise G = 1; R = 1.21 when race is black, otherwise R = 1
- Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease) [ Time Frame: 12 Months ]Participants with incidence of CMV (viremia, syndrome and disease). CMV is cytomegalovirus.
- Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy [ Time Frame: 12 Months ]Participants with Incidence of BKV (viremia, viruria, or nephropathy). BKV is Polyomavirus type BK.
- Number of Participants With Incidence of New Onset of Diabetes Mellitus [ Time Frame: 12 Months ]Incidence of new onset diabetes mellitus defined as non-diabetic patients before transplantation, who are receiving glucose lowering treatment for more than 30 days post-transplant, or with a random plasma glucose ≥200 mg dL (11.1 mmol/L) with 2 fasting plasma glucose values ≥126 mg/dL (7 mmol/L)
- Number of Participants With Incidence of Proteinuria Events [ Time Frame: Baseline and 12 Months ]Number of participants with Incidence of proteinuria events indicating chronic kidney disease
- Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events [ Time Frame: 12 Months ]Incidence of adverse events, serious adverse events, and tacrolimus-associated adverse events by System Organ Class
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01025817
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|