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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Transplantation
• Intervention / Treatment: Drug: Everolimus (RAD001)

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland
    • Novartis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate Everolimus; 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)
Experimental: Delayed Everolimus; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): April 4, 2011
• Last Update Submitted That Met QC Criteria: March 30, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: everolimus; Renal transplantation; immunosuppressants; wound-healing
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: CRAD001A2420