Efficacy and Safety of Early Versus Delayed Administration of Everolimus in de Novo Renal Transplant Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if the delayed administration of everolimus could reduce the everolimus associated anti-proliferative complications (e.g. wound healing disorder) while maintaining efficacy, when compared to the immediate administration of everolimus in de novo renal transplant patients.

Official Title
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A National Multicentre Randomized Study Comparing the Early Versus Delayed Administration of Everolimus in de Novo Kidney Transplant Recipients at Risk of Delayed Graft Function

Conditions
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Renal Transplantation

Intervention / Treatment
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* Drug: Everolimus (RAD001)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipients of cadaveric kidney transplants Patients at risk of DGF defined as one or more of the following: Donor age > 55 years Cold ischemic time (CIT) ≥ 24 hours but < 40 hours Second or subsequent renal transplantation Exclusion Criteria: Patients who have received an investigational drug within 4 weeks of baseline period Patients who are recipients of multiple organ transplants, including more than one kidney, or previous transplant with any organ other than kidney Patients with body mass index (BMI) > 32 kg/m2 Other protocol-defined exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate Everolimus<br>Patients received Everolimus starting within 48 hours of kidney transplant through to the end of the study, administered orally twice a day. Dose was adjusted in order to maintain a trough level between 3-8 ng/mL. | Drug: Everolimus (RAD001)<br> <br> |
| Experimental: Delayed Everolimus<br>Patients received Everolimus 4 weeks after kidney transplant until the end of the study, administered orally twice a day. The dose was adjusted in order to maintain a trough level between 3-8 ng/mL. Patients received mycophenolic acid until everolimus was initiated. | Drug: Everolimus (RAD001)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Considered in Failure for the Primary Failure Endpoint at 3 Months | In Failure, is at least one of these events occurred within the first 3 months: delayed graft function(DGF), (need for dialysis within the first 7 days,minus day one,post-transplantation); Biopsy proven acute rejection (BPAR), Graft loss, (allograft was presumed lost on the day the patient started and not removable from dialysis). Death; Loss to follow-up; Wound healing disorder(Any wound related to the kidney transplantation being opened beyond 3 weeks, or infected, or drained fluid or herniated was considered not healed). | Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Considered in Failure for the Primary Failure Endpoint at 6 Months Post-transplantation. | The primary efficacy variable was the primary failure endpoint at 6 months defined as the occurrence of one or more of the following events within the first 6 months: delayed graft function (DGF), defined as the need for dialysis within the first 7 days post-transplantation excluding the first day post-transplantation efficacy failure (biopsy proven acute rejection (BPAR), graft loss, death or loss to follow-up) wound healing disorder related to initial transplant surgery | at 6 Month post-transplantation | 
| Number of Participants Considered in Failure for the Primary Failure Endpoint at 12 Months Post-transplantation. | The primary efficacy variable was the primary failure endpoint at 12 months defined as the occurrence of one or more of the following events within the first 12 months: delayed graft function (DGF), defined as the need for dialysis within the first 7 days post-transplantation excluding the first day post-transplantation efficacy failure (biopsy proven acute rejection (BPAR), graft loss, death or loss to follow-up) wound healing disorder related to initial transplant surgery | at 12 Month post-transplantation | 
| Number of Participants Who Underwent Any Dialysis Within the 12-month Treatment Period | The number of patients who underwent any dialysis within the 12-month treatment period. | Month 12 | 
| Duration of Dialysis | The mean duration in days of any dialysis session that occurred within the 12 month treatment period. | 12 months | 
| Number of Participants With Any Wound Healing Disorder During the 12-month Treatment Period | A wound was considered healed if all the suture material and staples were removed and the wound was intact by 3 weeks. Any wound opened beyond this point, infected, drained fluid or herniated was considered not healed. | Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal transplantation, everolimus, immunosuppressants, wound-healing