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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00154297
First received: September 8, 2005
Last updated: March 30, 2011
Last verified: March 2011
  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:


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 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 April 14, 2014