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Everolimus in de Novo Kidney Transplant Recipients (NEVERWOUND)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01410448
First Posted: August 5, 2011
Last Update Posted: June 16, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose
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.

Condition Intervention Phase
Kidney Transplantation Drug: Everolimus Drug: Mycophenolate sodium Drug: Cyclosporine Drug: Steroids Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A 3-month, Multicenter, Randomized, Open Label Study to Evaluate the Impact of Early Versus Delayed Introduction of Everolimus on Wound Healing in de Novo Kidney Transplant Recipients With a Follow-up Evaluation at 12 Month After Transplant (NEVERWOUND Study)

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Percentage of Participants Without Wound Healing Complications - Worst-case Scenario [ Time Frame: 3 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:
  • Percentage of Participants Without Wound Healing Complications - Worst-case Scenario [ Time Frame: 12 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 Scenario [ Time Frame: 3 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 Scenario [ Time Frame: 3 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 Scenario [ Time Frame: 3 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 Scenario [ Time Frame: 3 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 Scenario [ Time Frame: 3 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) - [ Time Frame: 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 DGF [ Time Frame: 3 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 - ITT [ Time Frame: baseline, 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 ITT [ Time Frame: baseline, 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 - ITT [ Time Frame: baseline, 3 months ]
    Blood samples were collected to assess serum creatinine measurements. A negative change from baseline indicates improvement.

  • Change From Baseline in Serum Creatinine - Modified ITT [ Time Frame: baseline, 12 months ]
    Blood samples were collected to assess serum creatinine measurements. A negative change from baseline indicates improvement.

  • Percentage of Participants With Proteinuria [ Time Frame: 3 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) [ Time Frame: 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 Malignancy [ Time Frame: 12 months ]
    The percentage of participants with a new onset of malignancy was assessed.

  • Percentage of Participants With a New Onset of Diabetes [ Time Frame: 12 months ]
    The percentage of participants with a new onset of diabetes was assessed.


Enrollment: 383
Study Start Date: November 2011
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Immediate Everolimus (IE)
Everolimus 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.
Drug: Everolimus
Everolimus was provided in blisters containing 0.25 and 0.75 mg tablets and was taken orally.
Other Name: Certican®
Drug: Cyclosporine
Cyclosporine was supplied as blisters containing 100 mg, 50 mg, 25 mg and 10 mg soft-gelatin capsules and was administered orally.
Other Name: Neoral®
Drug: Steroids
Steroids were administered according to local clinical practice.
Experimental: Delayed Everolimus
The 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.
Drug: Everolimus
Everolimus was provided in blisters containing 0.25 and 0.75 mg tablets and was taken orally.
Other Name: Certican®
Drug: Mycophenolate sodium
Two 360 mg tablets were administered twice daily at 12-hour intervals. The tablets were swallowed whole in order to maintain the integrity of the enteric coating.
Other Name: Myfortic®
Drug: Cyclosporine
Cyclosporine was supplied as blisters containing 100 mg, 50 mg, 25 mg and 10 mg soft-gelatin capsules and was administered orally.
Other Name: Neoral®
Drug: Steroids
Steroids were administered according to local clinical practice.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion criteria:

  • Patients who are willing and able to participate in the study and who provide written informed consent before performing any study related procedure;
  • Men or women ≥18 years at transplant;
  • Recipients of 1st or 2nd single kidney transplant from deceased donor or living unrelated/related donor > 14 years;

Key Exclusion criteria:

  • Patients who are recipients of multiple organs transplant, including two kidneys;
  • Historical or current peak PRA > 50%. Patients with already existing antibodies against the donor;
  • Thrombocytopenia (platelets < 75,000/mm³), absolute neutrophil count <1,500/mm³, leucopenia (leucocytes < 2,500/mm³) or hemoglobin < 7 g/dL;
  • Body mass index (BMI) > 30 Kg/m2;
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01410448


Locations
Italy
Novartis Investigative Site
Ancona, AN, Italy, 60126
Novartis Investigative Site
Coppito, AQ, Italy, 67100
Novartis Investigative Site
Bari, BA, Italy, 70124
Novartis Investigative Site
Bologna, BO, Italy, 40138
Novartis Investigative Site
Brescia, BS, Italy, 25123
Novartis Investigative Site
Cagliari, CA, Italy, 09134
Novartis Investigative Site
Catania, CT, Italy, 95123
Novartis Investigative Site
Firenze, FI, Italy, 50139
Novartis Investigative Site
Milano, MI, Italy, 20132
Novartis Investigative Site
Milano, MI, Italy, 20162
Novartis Investigative Site
Modena, MO, Italy, 41100
Novartis Investigative Site
Palermo, PA, Italy, 90127
Novartis Investigative Site
Padova, PD, Italy, 35128
Novartis Investigative Site
Pavia, PV, Italy, 27100
Novartis Investigative Site
Roma, RM, Italy, 00144
Novartis Investigative Site
Roma, RM, Italy, 00152
Novartis Investigative Site
Roma, RM, Italy, 00161
Novartis Investigative Site
Roma, RM, Italy, 00168
Novartis Investigative Site
Salerno, SA, Italy, 84131
Novartis Investigative Site
Siena, SI, Italy, 53100
Novartis Investigative Site
Verona, VR, Italy, 37126
Novartis Investigative Site
Novara, Italy, 28100
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01410448     History of Changes
Other Study ID Numbers: CRAD001AIT25
2011-002866-19 ( EudraCT Number )
First Submitted: August 2, 2011
First Posted: August 5, 2011
Results First Submitted: November 21, 2016
Results First Posted: June 16, 2017
Last Update Posted: June 16, 2017
Last Verified: March 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Immunosuppression
Kidney transplantation
everolimus
safety

Additional relevant MeSH terms:
Everolimus
Sirolimus
Mycophenolic Acid
Cyclosporins
Cyclosporine
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents