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Everolimus in de Novo Kidney Transplant Recipients

Phase 3
Completed
Conditions
Kidney Transplantation
Interventions
Registration Number
NCT01410448
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

The purpose of this study was to evaluate whether delayed (i.e. 28 ± 4 days post-transplant) administration of everolimus after transplantation reduces the risk of wound healing complications in comparison with immediate administration in de novo renal transplant patients (proportion of patients without wound/surgical complications related to initial transplant surgery) between randomization and 3 months after transplantation.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
383
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Immediate Everolimus (IE)EverolimusEverolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
Immediate Everolimus (IE)CyclosporineEverolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
Immediate Everolimus (IE)SteroidsEverolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
Delayed EverolimusEverolimusThe standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
Delayed EverolimusCyclosporineThe standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
Delayed EverolimusSteroidsThe standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
Delayed EverolimusMycophenolate sodiumThe standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Without Wound Healing Complications - Worst-case Scenario3 months

The percentage of participants without wound healing complications was assessed. Wound healing complications consisted of lymphorrhea, fluid collections, wound dehiscence, wound infections and incisional hernia. In the worst-case scenario, failure, i.e. at least one healing complication occurrence, was identified in one of the following cases: wound complication occurrence, missing information about wound complication occurrence, or study discontinuation due to any reason.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Serum Creatinine - Modified ITTbaseline, 12 months

Blood samples were collected to assess serum creatinine measurements. A negative change from baseline indicates improvement.

Percentage of Participants With Proteinuria3 months

Incidence of proteinuria (\>1,000 mg/day in urine collected in 24 hours or \> 1.0 if measured on the urine protein/creatinine concentration ratio in a spot urine sample) was assessed.

Percentage of Participants With Acute Rejection (AR)12 months

AR was defined as an episode of increased serum creatinine \>30% that was clinically diagnosed as an acute rejection but was not biopsy proven.

Percentage of Participants With a New Onset of Malignancy12 months

The percentage of participants with a new onset of malignancy was assessed.

Percentage of Participants With a New Onset of Diabetes12 months

The percentage of participants with a new onset of diabetes was assessed.

Percentage of Participants Without Wound Healing Complications - Worst-case Scenario12 months

The percentage of participants without wound healing complications was assessed. Wound healing complications consisted of lymphorrhea, fluid collections, wound dehiscence, wound infections and incisional hernia. In the worst-case scenario, failure, i.e. at least one healing complication occurrence, was identified in one of the following cases: wound complication occurrence, missing information about wound complication occurrence or study discontinuation due to any reason for participants who did not complete the 12 month follow-up visit.

Percentage of Participants Who Experienced Treatment Failure - Worst-case Scenario3 months

The percentage of participants who experienced treatment failure was assessed. Treatment failure was defined as the occurrence of at least one failure event among death, graft loss or biopsy-proven acute rejection (BPAR). In the worst-case scenario, treatment failure was identified in one of the following cases: occurrence of at least one treatment failure event or study discontinuation due to any reason.

Patient Survival Rate: Percentage of Deaths - Worst-case Scenario3 Months, 12 months

The percentage of deaths was assessed. In the worst-case scenario, failure, i.e. death, was identified in one of the following cases: participant's death or study discontinuation due to any reason.

Participant/Graft Survival Rate: Percentage of Participants With Failure Events of Death or Graft Loss - Worst-case Scenario3 months

The percentage of participants who experienced death or graft loss was assessed. In the worst-case scenario, failure, i.e. participants death or graft loss, was identified in one of the following cases: occurrence of at least one failure event or study discontinuation due to any reason.

Graft Survival Rate: Percentage of Participants With Graft Loss - Worst-case Scenario3 months, 12 months

The percentage of participants who experienced graft loss was assessed. In the worst-case scenario, failure, i.e. graft loss, was identified in one of the following cases: occurrence of graft loss or discontinuation due to any reason.

Percentage of Participants With BPAR - Worst-case Scenario3 Months, 12 months

A biopsy-proven acute rejection was defined as a biopsy graded IA, IB, IIA, IIB or III. In the worst-case scenario, failure, i.e. BPAR, was identified in one of the following cases: occurrence of BPAR or study discontinuation due to any reason.

Percentage of Participants With Delayed Graft Function (DGF) -3 Months

DGF was defined as the need for dialysis in the first week after transplant, excluding Renal Replacement Therapy within the first 24 hours after transplantation.

Duration of DGF3 months

The duration of DGF was defined as the elapsed time from first to last day of post-transplant dialysis.

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) (Calculated With Modified Diet in Renal Disease (MDRD)-4 Formula - ITTbaseline, 3 Months

Renal function was assessed by measuring serum creatinine and serum urea and by calculating creatinine clearance using the MDRD-4 formula. eGFR = 186.3\*(serum creatinine \[mg/dL\])\^-1.154 \* (age at screening) -0.203 \* (0.742 if female) \* (1.21 if African American). A positive change from baseline indicates improvement.

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) (Calculated With Modified Diet in Renal Disease (MDRD)-4 Formula - Modified ITTbaseline, 12 months

Renal function was assessed by measuring serum creatinine and serum urea and by calculating creatinine clearance using the MDRD-4 formula. eGFR = 186.3\*(serum creatinine \[mg/dL\])\^-1.154 \* (age at screening) -0.203 \* (0.742 if female) \* (1.21 if African American). A positive change from baseline indicates improvement.

Change From Baseline in Serum Creatinine - ITTbaseline, 3 months

Blood samples were collected to assess serum creatinine measurements. A negative change from baseline indicates improvement.

Trial Locations

Locations (1)

Novartis Investigative Site

🇮🇹

Novara, Italy

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