Renal FunctionPhase 4NCT00634920
Evaluation of Early Conversion to Everolimus From Cyclosporine in de Novo Renal Transplant Recipients
A Phase 4 study testing everolimus, cyclosporine A and Enteric Coated Mycophenolate Sodium (EC-MPS) in people with Renal Function, run by Novartis Pharmaceuticals at 8 sites in 3 countries.
Trial summary
This study is designed to evaluate if early conversion to everolimus from cyclosporine in de novo renal transplant recipients can improve long-term renal function and slow down the progression of chronic allograft nephropathy Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Function
- What is being tested?
- everolimus, cyclosporine A and Enteric Coated Mycophenolate Sodium (EC-MPS)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 204 participants
- Where
- 8 sitesin 3 countries
- Study dates
- Mar 2008to May 2013
- Phase
- Phase 4
- 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
- First or second single renal transplant from deceased or living donor
- Patients maintained on a triple immunosuppressive regime consisting of cyclosporine, Enteric coated mycophenolate, and corticosteroids
- Patients completed the first 7 weeks without experiencing any rejection
Who cannot join
- Recipient of organs other than a renal transplant
- Present malignancy (within the last 2 years) other than excised basal cell or squamous cell carcinoma of the skin
- Severe liver disease
- At the time of randomization 7 weeks after transplantation
- In addition to the above criteria the following must be met at time of randomization:
- Graft loss
Show all 13Show fewer
- Low hemoglobin value, low number of white blood cells or platelets
- High cholesterol values
- Proteinuria
- Wound healing problems
- Current severe major local or systemic infection
- Renal insufficiency
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
Denmark4 sites
Novartis Investigative Site
Aarhus N, 8200
Novartis Investigative Site
Copenhagen, DK-2100
Novartis Investigative Site
Herlev, 2730
Novartis Investigative Site
Odense C, DK-5000
Sweden3 sites
Novartis Investigative Site
Gothenburg, 413 45
Novartis Investigative Site
Malmö, 205 02
Novartis Investigative Site
Uppsala, 751 85
About this study
Official title: A Controlled Randomized Open-label Multicenter Study Evaluating if Early Conversion to Everolimus (Certican) From Cyclosporine (Neoral) in de Novo Renal Transplant Recipients Can Improve Long-term Renal Function and Slow Down the Progression of Chronic Allograft Nephropathy
This study is designed to evaluate if early conversion to everolimus from cyclosporine in de novo renal transplant recipients can improve long-term renal function and slow down the progression of chronic allograft nephropathy
- Conditions
- Renal Function
- Being tested
- everolimus, cyclosporine A, Enteric Coated Mycophenolate Sodium (EC-MPS), corticosteroids, Basiliximab
- Keywords
- De novo renal transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called Certican
Everolimus (Certican®) tablets administered orally in two divided doses (b.i.d.) at a starting dose of 4 mg/day adjusted to target a trough blood concentration between 6 and 10 ng/mL in period 2.
cyclosporine ADrug
Also called Sndimmun Neoral
CsA (Sandimmun Neoral), based on C0-h levels 75-200 ng/mL or C2-h levels 700 900 ng/mL from randomization to Month 6, or C0-h levels 50-150 ng/mL or C2-h levels 600 800 ng/mL from Month 6 to Month 36, according to local method
Enteric Coated Mycophenolate Sodium (EC-MPS)Drug
Also called Myfortic
Target dose 1440 mg in the control group, target dose 1080 in the everolimus group (higher dose in the CsA group because of interactions of CsA on gastric reabsorption of mycophenolate)
corticosteroidsDrug
Also called Prednisolone
For both groups: minimum corticosteroid dose of 10 mg until week 12, 5-10 mg until month 12, month 12-36 corticosteroid treatment on investigator's descretion.
BasiliximabDrug
Also called Simulect
Induction therapy 20 mg basiliximab on Day 0 prior to reperfusion and 20 mg on Day 4 post-TX.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus (CNI-free) | Experimental | Patients in this group were converted to everolimus immunosuppressive therapy. The patients in the everolimus group were treated with everolimus, off-label (CNI-free) use, and EC-MPS and corticosteroids in accordance with local practice and approved label. Conversion to everolimus was as follows: Day 1: begin everolimus 3 mg in the evening. Usual morning dose of CsA and 50% reduced evening dose of CsA Day 2: everolimus 2 mg in the morning and 2 mg in the evening, complete discontinuation of CsA Day 3 or 4, and onwards: everolimus according to trough level 6-10 ng/mL.The given total daily dose of the immunosuppressive drugs (everolimus) was divided into two (equal) doses, applied 12 hours apart. Receives: Drug: everolimus; Drug: Enteric Coated Mycophenolate Sodium (EC-MPS); Drug: corticosteroids; Drug: Basiliximab |
| Control (CsA) | Active comparator | Patients in the control group continued on an immunosuppressive regimen. The patients in this Control group were treated with CsA, EC-MPS and corticosteroids in accordance with local practice and approved label. The given total daily dose of the immunosuppressive drugs (CsA and EC-MPS) was divided into two (equal) doses, applied 12 hours apart. Receives: Drug: cyclosporine A; Drug: Enteric Coated Mycophenolate Sodium (EC-MPS); Drug: corticosteroids; Drug: Basiliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measured Glomerular Filtration Rate
To compare the efficacy between treatment regimens by assessing the difference in renal function evaluated by mean measured glomerular filtration rate (mGFR) 12 months after renal transplantation (TX). The mGFR was measured using Iohexol or Cr-EDTA clearance according to local practice.
Measured: Month 12
Secondary outcomes (18)
Measured Glomerular Filtration Rate
Progression of renal function measured by mean mGFR at 36 months after renal TX. The mGFR was measured using Iohexol or Cr-EDTA clearance according to local practice.
Measured: Month 36
Calculated Glomerular Filtration Rate
The GFR was calculated according to the Modification of Diet in Renal Disease Study Group (MDRD) method, the Cockcroft-Gault method, and the Nankivell formula. cGFR was calculated from blood samples collected at predefined time points.
Measured: Months 12, 36
Progression of Measured Glomerular Filtration Rate
Change in renal progression measured by mean mGFR from week 7 to Month 36
Measured: Week 7, Week 52, Month 36
Percentage of Participants Who Developed CAN (Chronic Allograft Nephropathy)
Assessed by protocol biopsies findings (Banff 1997 lesion scores and morphometry of the interstitial space)
Measured: Month 12, Month 36
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
A BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III (Banff 97 classification). Biopsy graded IA: Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Biopsy grade IB: Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Biopsy grade IIA: Mild to moderate intimal arteritis. Biopsy graded IIB: Severe intimal arteritis comprising > 25% of the lumenal area.
Measured: Months 12, 24, 36
Percentage of Participants With Graft Loss or Death
The allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, the day of nephrectomy was the day of graft loss. Graft loss was considered an SAE (serious adverse event).
Measured: Months 12, 24, 36
Time to Treatment Failure
Treatment failure was defined as graft loss or death.Time to treatment failure is shown as mean time to treatment failure.
Measured: Months 12, 24, 36
Percentage of Participants With Treatment Failures
Treatment failure was defined as graft loss or death.
Measured: Months 12, 24, 36
Time to First Malignancy
This is the time to first diagnosed malignancy. Malignancies (skin- or solid cancer) were listed whether they reoccurred in situ, were metastatic or de novo. This is shown as mean time.
Measured: Months 12, 24, 36
Lipid Profile for Apolipoprotein
Blood lipid levels of patients in both groups for Apolipoprotein (Apo) A1 and B.
Measured: Months 12, 24, 36
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Blood lipid levels of patients in both groups: HDL-C, LDL-C,Total cholesterol, and triglycerides.
Measured: Months 12, 24, 36
Number of Lipid-lowering Drugs Taken
Measured: Months 12, 24, 36
Percentage of Participants on Lipid-lowering Drugs
Measured: Months 12, 24, 36
Number of Antihypertensive Drugs Taken
Measured: Months 12, 24, 36
Percentage of Participants on Antihypertensive Drugs
Measured: Months 12, 24, 36
Proteinuria (Measured as Urine Albumin/Creatinine Ratio (mg/mmol))
Proteinuria is when a large amount of protein, that should remain circulating in a person's blood, is "spilled" into their urine and eliminated from the body.
Measured: Months 12, 24, 36
Percentage of Participants Who Had Donor Specific Antibodies (DSA)
Venous blood was drawn for donor specific (DSA) measurements prior to transplantation and at the final visit (36 months). The blood sample was first screened for the presence of PRA i.e. donor specific Immunoglobulin-G antibodies against specific HLA antigens. If PRA antibodies were detected, the blood sample was tested for specific DSAs on single antigen Luminex beads (coated with single HLA class I or II molecules). In this way, the specificity of these antibodies could be determined.
Measured: Month 36
Health-related Quality of Life (QoL) as Measured by EuroQoL EQ-5D
Health-related QoL was assessed using the EQ-5D questionnaire. The EQ-5D self-report questionnaire consists of the EQ-5D descriptive system that measures health-related quality of life on 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which can take one of three responses. The responses record three levels of severity (no problems/moderate problems/severe problems) within a particular EQ-5D dimension. Scores are transformed to a range of 0-1, in which higher scores reflect better health status.
Measured: Before randomization, Months 12, 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2008 (estimated)
- Study startMar 2008
- Primary completionMay 2013
- Study completionMay 2013
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 Renal FunctionStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 204 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
- NCT00634920
- Sponsor's protocol ID
- CRAD001ASE01
- Other IDs
- 2007-000771-42
- Status last verified
- Aug 2014
- First submitted
- 6 Mar 2008
- Last updated
- 13 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Controlled Randomized Open-label Multicenter Study Evaluating if Early Conversion to Everolimus (Certican) From Cyclosporine (Neoral) in de Novo Renal Transplant Recipients Can Improve Long-term Renal Function and Slow Down the Progression of Chronic Allograft Nephropathy
- ClinicalTrials.gov ID
- NCT00634920
- Acronym / sponsor ID
- CRAD001ASE01
- Conditions
- Renal Function
- Keywords
- De novo renal transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 204 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Mar 2008
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 13 Mar 2008 (estimated)
- Results
- Posted 13 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate if early conversion to everolimus from cyclosporine in de novo renal transplant recipients can improve long-term renal function and slow down the progression of chronic allograft nephropathy
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus (CNI-free) | Experimental | Drug: everolimus, Drug: Enteric Coated Mycophenolate Sodium (EC-MPS), Drug: corticosteroids, Drug: BasiliximabPatients in this group were converted to everolimus immunosuppressive therapy. The patients in the everolimus group were treated with everolimus, off-label (CNI-free) use, and EC-MPS and corticosteroids in accordance with local practice and approved label. Conversion to everolimus was as follows: Day 1: begin everolimus 3 mg in the evening. Usual morning dose of CsA and 50% reduced evening dose of CsA Day 2: everolimus 2 mg in the morning and 2 mg in the evening, complete discontinuation of CsA Day 3 or 4, and onwards: everolimus according to trough level 6-10 ng/mL.The given total daily dose of the immunosuppressive drugs (everolimus) was divided into two (equal) doses, applied 12 hours apart. |
| Control (CsA) | Active comparator | Drug: cyclosporine A, Drug: Enteric Coated Mycophenolate Sodium (EC-MPS), Drug: corticosteroids, Drug: BasiliximabPatients in the control group continued on an immunosuppressive regimen. The patients in this Control group were treated with CsA, EC-MPS and corticosteroids in accordance with local practice and approved label. The given total daily dose of the immunosuppressive drugs (CsA and EC-MPS) was divided into two (equal) doses, applied 12 hours apart. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- First or second single renal transplant from deceased or living donor
- Patients maintained on a triple immunosuppressive regime consisting of cyclosporine, Enteric coated mycophenolate, and corticosteroids
- Patients completed the first 7 weeks without experiencing any rejection
Key exclusion criteria (13 listed)
- Recipient of organs other than a renal transplant
- Present malignancy (within the last 2 years) other than excised basal cell or squamous cell carcinoma of the skin
- Severe liver disease
- At the time of randomization 7 weeks after transplantation
- Graft loss
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: CerticanEverolimus (Certican®) tablets administered orally in two divided doses (b.i.d.) at a starting dose of 4 mg/day adjusted to target a trough blood concentration between 6 and 10 ng/mL in period 2. | Drug | Everolimus (CNI-free) |
| cyclosporine AAlso: Sndimmun NeoralCsA (Sandimmun Neoral), based on C0-h levels 75-200 ng/mL or C2-h levels 700 900 ng/mL from randomization to Month 6, or C0-h levels 50-150 ng/mL or C2-h levels 600 800 ng/mL from Month 6 to Month 36, according to local method | Drug | Control (CsA) |
| Enteric Coated Mycophenolate Sodium (EC-MPS)Also: MyforticTarget dose 1440 mg in the control group, target dose 1080 in the everolimus group (higher dose in the CsA group because of interactions of CsA on gastric reabsorption of mycophenolate) | Drug | Control (CsA), Everolimus (CNI-free) |
| corticosteroidsAlso: PrednisoloneFor both groups: minimum corticosteroid dose of 10 mg until week 12, 5-10 mg until month 12, month 12-36 corticosteroid treatment on investigator's descretion. | Drug | Control (CsA), Everolimus (CNI-free) |
| BasiliximabAlso: SimulectInduction therapy 20 mg basiliximab on Day 0 prior to reperfusion and 20 mg on Day 4 post-TX. | Drug | Control (CsA), Everolimus (CNI-free) |
Primary outcome
Measured Glomerular Filtration Rate
Time frame: Month 12
To compare the efficacy between treatment regimens by assessing the difference in renal function evaluated by mean measured glomerular filtration rate (mGFR) 12 months after renal transplantation (TX). The mGFR was measured using Iohexol or Cr-EDTA clearance according to local practice.
18 secondary outcomes
Measured Glomerular Filtration Rate
Time frame: Month 36
Calculated Glomerular Filtration Rate
Time frame: Months 12, 36
Progression of Measured Glomerular Filtration Rate
Time frame: Week 7, Week 52, Month 36
Percentage of Participants Who Developed CAN (Chronic Allograft Nephropathy)
Time frame: Month 12, Month 36
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Time frame: Months 12, 24, 36
Percentage of Participants With Graft Loss or Death
Time frame: Months 12, 24, 36
Time to Treatment Failure
Time frame: Months 12, 24, 36
Percentage of Participants With Treatment Failures
Time frame: Months 12, 24, 36
Time to First Malignancy
Time frame: Months 12, 24, 36
Lipid Profile for Apolipoprotein
Time frame: Months 12, 24, 36
Lipid Profile for HDL-C, LDL-C,Total Cholesterol, and Triglycerides
Time frame: Months 12, 24, 36
Number of Lipid-lowering Drugs Taken
Time frame: Months 12, 24, 36
Percentage of Participants on Lipid-lowering Drugs
Time frame: Months 12, 24, 36
Number of Antihypertensive Drugs Taken
Time frame: Months 12, 24, 36
Percentage of Participants on Antihypertensive Drugs
Time frame: Months 12, 24, 36
Proteinuria (Measured as Urine Albumin/Creatinine Ratio (mg/mmol))
Time frame: Months 12, 24, 36
Percentage of Participants Who Had Donor Specific Antibodies (DSA)
Time frame: Month 36
Health-related Quality of Life (QoL) as Measured by EuroQoL EQ-5D
Time frame: Before randomization, Months 12, 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2014.
- 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
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing everolimus, cyclosporine A and Enteric Coated Mycophenolate Sodium (EC-MPS) in people with Renal Function, run by Novartis Pharmaceuticals at 8 sites in 3 countries.
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 13 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 13 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Denmark, Sweden, Norway. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 13 Aug 2014). 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?
Measured Glomerular Filtration Rate (time frame: Month 12). 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 13 Aug 2014.