Kidney TransplantationPhase 3NEVERWOUNDNCT01410448
Everolimus in de Novo Kidney Transplant Recipients
A Phase 3 study testing Everolimus, Mycophenolate sodium and Cyclosporine in people with Kidney Transplantation, run by Novartis Pharmaceuticals at 22 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Everolimus, Mycophenolate sodium and Cyclosporine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 383 participants
- Where
- 22 sitesItaly
- Study dates
- Nov 2011to Dec 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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;
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
Italy22 sites
Novartis Investigative Site
Ancona, AN, 60126
Novartis Investigative Site
Bari, BA, 70124
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Brescia, BS, 25123
Novartis Investigative Site
Cagliari, CA, 09134
Novartis Investigative Site
Catania, CT, 95123
Novartis Investigative Site
Coppito, AQ, 67100
Novartis Investigative Site
Florence, FI, 50139
Novartis Investigative Site
Milan, MI, 20132
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Modena, MO, 41100
Novartis Investigative Site
Novara, 28100
Novartis Investigative Site
Padova, PD, 35128
Novartis Investigative Site
Palermo, PA, 90127
Novartis Investigative Site
Pavia, PV, 27100
Novartis Investigative Site
Roma, RM, 00144
Novartis Investigative Site
Roma, RM, 00152
Novartis Investigative Site
Roma, RM, 00161
Novartis Investigative Site
Roma, RM, 00168
Novartis Investigative Site
Salerno, SA, 84131
Novartis Investigative Site
Siena, SI, 53100
Novartis Investigative Site
Verona, VR, 37126
About this study
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)
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.
- Conditions
- Kidney Transplantation
- Being tested
- Everolimus, Mycophenolate sodium, Cyclosporine, Steroids
- Keywords
- Immunosuppression, Kidney transplantation, everolimus, safety
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Certican®
Everolimus was provided in blisters containing 0.25 and 0.75 mg tablets and was taken orally.
Mycophenolate sodiumDrug
Also called Myfortic®
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.
CyclosporineDrug
Also called Neoral®
Cyclosporine was supplied as blisters containing 100 mg, 50 mg, 25 mg and 10 mg soft-gelatin capsules and was administered orally.
SteroidsDrug
Steroids were administered according to local clinical practice.
| Study group | Role | What they receive |
|---|---|---|
| Immediate Everolimus (IE) | Active comparator | 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. Receives: Drug: Everolimus; Drug: Cyclosporine; Drug: Steroids |
| Delayed Everolimus | Experimental | 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. Receives: Drug: Everolimus; Drug: Mycophenolate sodium; Drug: Cyclosporine; Drug: Steroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Without Wound Healing Complications - Worst-case Scenario
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.
Measured: 3 months
Secondary outcomes (16)
Percentage of Participants Without Wound Healing Complications - Worst-case Scenario
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.
Measured: 12 months
Percentage of Participants Who Experienced Treatment Failure - Worst-case Scenario
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.
Measured: 3 months
Patient Survival Rate: Percentage of Deaths - Worst-case Scenario
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.
Measured: 3 Months, 12 months
Participant/Graft Survival Rate: Percentage of Participants With Failure Events of Death or Graft Loss - Worst-case Scenario
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.
Measured: 3 months
Graft Survival Rate: Percentage of Participants With Graft Loss - Worst-case Scenario
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.
Measured: 3 months, 12 months
Percentage of Participants With BPAR - Worst-case Scenario
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.
Measured: 3 Months, 12 months
Percentage of Participants With Delayed Graft Function (DGF) -
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.
Measured: 3 Months
Duration of DGF
The duration of DGF was defined as the elapsed time from first to last day of post-transplant dialysis.
Measured: 3 months
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) (Calculated With Modified Diet in Renal Disease (MDRD)-4 Formula - ITT
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.
Measured: baseline, 3 Months
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) (Calculated With Modified Diet in Renal Disease (MDRD)-4 Formula - Modified ITT
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.
Measured: baseline, 12 months
Change From Baseline in Serum Creatinine - ITT
Blood samples were collected to assess serum creatinine measurements. A negative change from baseline indicates improvement.
Measured: baseline, 3 months
Change From Baseline in Serum Creatinine - Modified ITT
Blood samples were collected to assess serum creatinine measurements. A negative change from baseline indicates improvement.
Measured: baseline, 12 months
Percentage of Participants With Proteinuria
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.
Measured: 3 months
Percentage of Participants With Acute Rejection (AR)
AR was defined as an episode of increased serum creatinine >30% that was clinically diagnosed as an acute rejection but was not biopsy proven.
Measured: 12 months
Percentage of Participants With a New Onset of Malignancy
The percentage of participants with a new onset of malignancy was assessed.
Measured: 12 months
Percentage of Participants With a New Onset of Diabetes
The percentage of participants with a new onset of diabetes was assessed.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2011 (estimated)
- Study startNov 2011
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 383 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01410448
- Sponsor's protocol ID
- CRAD001AIT25
- Other IDs
- 2011-002866-19
- Acronym
- NEVERWOUND
- Status last verified
- Mar 2017
- First submitted
- 2 Aug 2011
- Last updated
- 16 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01410448
- Acronym / sponsor ID
- NEVERWOUND / CRAD001AIT25
- Conditions
- Kidney Transplantation
- Keywords
- Immunosuppression, Kidney transplantation, everolimus, safety
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 383 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 5 Aug 2011 (estimated)
- Results
- Posted 16 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immediate Everolimus (IE) | Active comparator | Drug: Everolimus, Drug: Cyclosporine, Drug: 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 Everolimus | Experimental | Drug: Everolimus, Drug: Mycophenolate sodium, Drug: Cyclosporine, Drug: SteroidsThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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 (4 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: Certican®Everolimus was provided in blisters containing 0.25 and 0.75 mg tablets and was taken orally. | Drug | Delayed Everolimus, Immediate Everolimus (IE) |
| Mycophenolate sodiumAlso: Myfortic®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. | Drug | Delayed Everolimus |
| CyclosporineAlso: Neoral®Cyclosporine was supplied as blisters containing 100 mg, 50 mg, 25 mg and 10 mg soft-gelatin capsules and was administered orally. | Drug | Delayed Everolimus, Immediate Everolimus (IE) |
| SteroidsSteroids were administered according to local clinical practice. | Drug | Delayed Everolimus, Immediate Everolimus (IE) |
Primary outcome
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.
16 secondary outcomes
Percentage of Participants Without Wound Healing Complications - Worst-case Scenario
Time frame: 12 months
Percentage of Participants Who Experienced Treatment Failure - Worst-case Scenario
Time frame: 3 months
Patient Survival Rate: Percentage of Deaths - Worst-case Scenario
Time frame: 3 Months, 12 months
Participant/Graft Survival Rate: Percentage of Participants With Failure Events of Death or Graft Loss - Worst-case Scenario
Time frame: 3 months
Graft Survival Rate: Percentage of Participants With Graft Loss - Worst-case Scenario
Time frame: 3 months, 12 months
Percentage of Participants With BPAR - Worst-case Scenario
Time frame: 3 Months, 12 months
Percentage of Participants With Delayed Graft Function (DGF) -
Time frame: 3 Months
Duration of DGF
Time frame: 3 months
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
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
Change From Baseline in Serum Creatinine - ITT
Time frame: baseline, 3 months
Change From Baseline in Serum Creatinine - Modified ITT
Time frame: baseline, 12 months
Percentage of Participants With Proteinuria
Time frame: 3 months
Percentage of Participants With Acute Rejection (AR)
Time frame: 12 months
Percentage of Participants With a New Onset of Malignancy
Time frame: 12 months
Percentage of Participants With a New Onset of Diabetes
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Everolimus, Mycophenolate sodium and Cyclosporine in people with Kidney Transplantation, run by Novartis Pharmaceuticals at 22 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Without Wound Healing Complications - Worst-case Scenario (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2017.