Efficacy and Safety of Early Versus Delayed Administration of Everolimus in de Novo Renal Transplant Patients - Full Text View

Purpose

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.

Condition	Intervention	Phase
Renal Transplantation	Drug: Everolimus (RAD001)	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Sirolimus Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Number of Participants Considered in Failure for the Primary Failure Endpoint at 3 Months [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
"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).

Secondary Outcome Measures:

Number of Participants Considered in Failure for the Primary Failure Endpoint at 6 Months Post-transplantation. [ Time Frame: at 6 Month post-transplantation ] [ Designated as safety issue: No ]
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
Number of Participants Considered in Failure for the Primary Failure Endpoint at 12 Months Post-transplantation. [ Time Frame: at 12 Month post-transplantation ] [ Designated as safety issue: No ]
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
Number of Participants Who Underwent Any Dialysis Within the 12-month Treatment Period [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
The number of patients who underwent any dialysis within the 12-month treatment period.
Duration of Dialysis [ Time Frame: 12 months ] [ Designated as safety issue: No ]
The mean duration in days of any dialysis session that occurred within the 12 month treatment period.
Number of Participants With Any Wound Healing Disorder During the 12-month Treatment Period [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
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.

Enrollment:	139
Study Start Date:	June 2005
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00154297

Locations

Switzerland
Novartis
Basel, Switzerland

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00154297 History of Changes
Other Study ID Numbers:	CRAD001A2420
Study First Received:	September 8, 2005
Results First Received:	January 4, 2011
Last Updated:	March 30, 2011
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Novartis:

Renal transplantation
everolimus
immunosuppressants
wound-healing

Additional relevant MeSH terms:

Delayed Graft Function
Pathologic Processes
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 16, 2013