Renal TransplantationPhase 4NCT00369161

A Twelve-month, Multicenter, Open-label, Randomized Study of the Safety, Tolerability and Efficacy of Everolimus With Basiliximab, Corticosteroids and Two Different Exposure Levels of Tacrolimus in de Novo Renal Transplant Recipients

A Phase 4 study testing Everolimus (RAD001), Tacrolimus and Basiliximab in people with Renal Transplantation, run by Novartis at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study is designed to evaluate whether tacrolimus dose reduction in de novo renal recipients receiving everolimus can preserve renal function while maintaining efficacy. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Renal Transplantation
What is being tested?: Everolimus (RAD001), Tacrolimus and Basiliximab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 228 participants
Where: 1 siteSwitzerland
Study dates: Jun 2006to Dec 2008
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 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female of 18-65 years old
Patient who has received a primary kidney transplant from a cadaveric, living unrelated or non-human leucocyte antigen (HLA) identical living related donor
Recipient of a kidney with a cold ischemia time (CIT) < 30 hours
Recipient of a kidney from a donor 10-65 years old
Patient able to receive the first dose of tacrolimus within 24 hours from graft reperfusion
Female capable of becoming pregnant must have a negative pregnancy test and is required to practice a medically approved method of birth control for the duration of the study and for a period of three months following discontinuation of investigational drug
Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months

Who cannot join

Patient who has previously received an organ transplant
Recipient of multiple organ transplants
Recipient of a kidney transplant from a non heart-beating donor
Recipient of donor specific transfusions
Recipient of A-B-O incompatible transplant or T-cell cross-match positive transplant
Patient with current Panel Reactive Antibodies (PRA) level ≥ 50%

Show all 20Show fewer

Recipient of a kidney from a donor who tests positive for hepatitis B surface antigen or hepatitis C antibodies
Patient who is human immunodeficiency virus (HIV) positive
Patient who has a positive hepatitis C serology or who is hepatitis B surface antigen positive with evidence of liver injury as indicated by aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels ≥2.5 times upper limit of normal (UNL). Viral serology results obtained within 6 months prior to the administration of the first dose of Certican™ are acceptable
Patient with severe hypercholesterolemia (350 mg/dL, 9.1 mmoL/dL) or hypertriglyceridemia ( 500 mg/dL, 5.6 mmoL/L)
Patient with white blood cell (WBC) count 3,000/mm3 or with platelet count 75,000/mm3
Patient with any severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment, or with hypersensitivity to drugs similar to Certican (e.g., macrolides)
Patient who has been treated with an immunosuppressive drug or an investigational drug within 4 weeks prior to the administration of the first dose of Certican
Patient with uncontrolled infection
Patient with any surgical or medical condition, other than the current transplant, which in the opinion of the investigator, precludes enrollment in this trial
Patient with a known malignancy or a history of malignancy within last 5 years other than successfully treated localized basal or squamous cell carcinoma of the skin
Abnormal physical or laboratory findings of clinical significance within 2 weeks prior to the administration of the first dose of Certican™ which at investigator's discretion would interfere with the objectives of the study
Breast feeding women
Patient with symptoms of significant somatic or mental illness or with unresolved history of drug or alcohol abuse
Patient unable to cooperate or communicate with the investigator

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

Novartis
Basel

Other trials in Switzerland

About this study

Official title: A Twelve-month, Multicenter, Open-label, Randomized Study of the Safety, Tolerability and Efficacy of Everolimus With IL-2 Receptor Antagonist, Corticosteroids and Two Different Exposure Levels of Tacrolimus in de Novo Renal Transplant Recipients

This study is designed to evaluate whether tacrolimus dose reduction in de novo renal recipients receiving everolimus can preserve renal function while maintaining efficacy.

Conditions: Renal Transplantation
Being tested: Everolimus (RAD001), Tacrolimus, Basiliximab, Corticosteroids

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Everolimus (RAD001)Drug
TacrolimusDrug
BasiliximabDrug
CorticosteroidsDrug

Study groups in NCT00369161
Study group	Role	What they receive
Very low dose tacrolimus	Active comparator	The first dose of everolimus was to be administered not later than 24 hours after transplantation with a starting dose of 1.5 mg bis in diem/twice a day (b.i.d.) thereafter adjusted to maintain the trough blood levels between 3 and 8 ng/ml. Tacrolimus was to be initiated within 24 hours after reperfusion of the graft with a starting dose of 0.1 mg/kg/day thereafter adjusted to maintain the trough blood levels between 4 and 7 ng/ml. Up to months three all patients received the same treatment and after three months patients in this arm received tacrolimus to reach a trough blood level between 1.5 and 3 ng/ml. All patients received two doses of 20 mg basiliximab, administered as an intravenous bolus injection. The first dose was given on the day of transplantation, with the second dose being administered on the fourth day post-transplant. Intravenous (i.v.) prednisone (or equivalent) was given pre- or intra-operatively according to center practice. Receives: Drug: Everolimus (RAD001); Drug: Tacrolimus; Drug: Basiliximab; Drug: Corticosteroids
Low dose tacrolimus	Active comparator	The first dose of everolimus was to be administered not later than 24 hours after transplantation with a starting dose of 1.5 mg bis in diem/twice a day (b.i.d.) thereafter adjusted to maintain the trough blood levels between 3 and 8 ng/ml. Tacrolimus was to be initiated within 24 hours after reperfusion of the graft with a starting dose of 0.1 mg/kg/day thereafter adjusted to maintain the trough blood levels between 4 and 7 ng/ml. Up to months three all patients received the same treatment and after three months patients in this arm received tacrolimus to reach a trough blood level between 4 and 7 ng/ml. All patients received two doses of 20 mg basiliximab, administered as an intravenous bolus injection. The first dose was given on the day of transplantation, with the second dose being administered on the fourth day post-transplant. Intravenous (i.v.) prednisone (or equivalent) was given pre- or intra-operatively according to center practice. Receives: Drug: Everolimus (RAD001); Drug: Tacrolimus; Drug: Basiliximab; Drug: Corticosteroids

What is being measured

The primary outcome is the main question the study is designed to answer.

Renal Function Assessed by Calculated Glomerular Filtration Rate (cGFR)
Renal function was assessed by calculated glomerular filtration rate (cGFR) using Modification of Diet in Renal Disease (MDRD)formula.
GFR [mL/min/1.73m^2] = 186.3*(C-1.154)*(A-0.203)*G*R, where:
- C is the serum concentration of creatinine [mg/dL],
- A is patient age at sample collection date [years],
- G=0.742 when gender is female, otherwise G=1,
- R=1.21 when race is black, otherwise R=1
Measured: 12 months post -transplant

Secondary outcomes (2)

Number of Participants With Incidence of Biopsy-proven Acute Rejection (BPAR)
Biopsy-proven acute rejection (BPAR) was defined as a clinically suspected acute rejection confirmed by biopsy (performed by the local pathologist). For all clinically suspected rejection episodes a graft core biopsy must have been performed before or within a 24 hour period from the initiation of anti-rejection therapy.
Measured: from Month 4 through to Month 12
Percentage of Participants With Efficacy Failure
Efficacy failure was a composite of BPAR, graft loss, death or lost to follow-up. BPAR was defined as a clinically suspected acute rejection confirmed by biopsy (performed by the local pathologist). For all clinically suspected rejection episodes a graft core biopsy must have been performed before or within a 24 hour period from the initiation of anti-rejection therapy. An allograft was presumed to be lost on the day a patient started dialysis and was unable to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, the day of nephrectomy was the day of graft loss.
Measured: Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2006Dec 2008

First posted29 Aug 2006 (estimated)
Study startJun 2006
Primary completionDec 2008
Study completionDec 2008

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Renal TransplantationStudies of the same condition, open and under way.
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: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 228 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00369161
Sponsor's protocol ID: CRAD001A2426
Status last verified: Feb 2017
First submitted: 25 Aug 2006
Last updated: 3 Mar 2017
Results posted: Yes, on ClinicalTrials.gov

Publications

Langer RM, Hene R, Vitko S, Christiaans M, Tedesco-Silva H Jr, Ciechanowski K, Cassuto E, Rostaing L, Vilatoba M, Machein U, Ulbricht B, Junge G, Dong G, Pascual J. Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multicentre trial in renal transplantation. Transpl Int. 2012 May;25(5):592-602. doi: 10.1111/j.1432-2277.2012.01465.x. Epub 2012 Mar 26.
PubMed 22471345

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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RecruitingPhase 2
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Microvascular Inflammation
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All Renal Transplantation trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Twelve-month, Multicenter, Open-label, Randomized Study of the Safety, Tolerability and Efficacy of Everolimus With IL-2 Receptor Antagonist, Corticosteroids and Two Different Exposure Levels of Tacrolimus in de Novo Renal Transplant Recipients
ClinicalTrials.gov ID: NCT00369161
Acronym / sponsor ID: CRAD001A2426
Conditions: Renal Transplantation
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 228 participants (actual)
Lead sponsor: NovartisIndustry (pharma, biotech, devices)
Study start: Jun 2006
Primary completion: Dec 2008 (actual)
Study completion: Dec 2008 (actual)
First posted: 29 Aug 2006 (estimated)
Results: Posted 19 Jan 2011

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 whether tacrolimus dose reduction in de novo renal recipients receiving everolimus can preserve renal function while maintaining efficacy.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Very low dose tacrolimus	Active comparator	Drug: Everolimus (RAD001), Drug: Tacrolimus, Drug: Basiliximab, Drug: CorticosteroidsThe first dose of everolimus was to be administered not later than 24 hours after transplantation with a starting dose of 1.5 mg bis in diem/twice a day (b.i.d.) thereafter adjusted to maintain the trough blood levels between 3 and 8 ng/ml. Tacrolimus was to be initiated within 24 hours after reperfusion of the graft with a starting dose of 0.1 mg/kg/day thereafter adjusted to maintain the trough blood levels between 4 and 7 ng/ml. Up to months three all patients received the same treatment and after three months patients in this arm received tacrolimus to reach a trough blood level between 1.5 and 3 ng/ml. All patients received two doses of 20 mg basiliximab, administered as an intravenous bolus injection. The first dose was given on the day of transplantation, with the second dose being administered on the fourth day post-transplant. Intravenous (i.v.) prednisone (or equivalent) was given pre- or intra-operatively according to center practice.
Low dose tacrolimus	Active comparator	Drug: Everolimus (RAD001), Drug: Tacrolimus, Drug: Basiliximab, Drug: CorticosteroidsThe first dose of everolimus was to be administered not later than 24 hours after transplantation with a starting dose of 1.5 mg bis in diem/twice a day (b.i.d.) thereafter adjusted to maintain the trough blood levels between 3 and 8 ng/ml. Tacrolimus was to be initiated within 24 hours after reperfusion of the graft with a starting dose of 0.1 mg/kg/day thereafter adjusted to maintain the trough blood levels between 4 and 7 ng/ml. Up to months three all patients received the same treatment and after three months patients in this arm received tacrolimus to reach a trough blood level between 4 and 7 ng/ml. All patients received two doses of 20 mg basiliximab, administered as an intravenous bolus injection. The first dose was given on the day of transplantation, with the second dose being administered on the fourth day post-transplant. Intravenous (i.v.) prednisone (or equivalent) was given pre- or intra-operatively according to center practice.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Male or female of 18-65 years old
Patient who has received a primary kidney transplant from a cadaveric, living unrelated or non-human leucocyte antigen (HLA) identical living related donor
Recipient of a kidney with a cold ischemia time (CIT) < 30 hours
Recipient of a kidney from a donor 10-65 years old
Patient able to receive the first dose of tacrolimus within 24 hours from graft reperfusion

Key exclusion criteria (20 listed)

Patient who has previously received an organ transplant
Recipient of multiple organ transplants
Recipient of a kidney transplant from a non heart-beating donor
Recipient of donor specific transfusions
Recipient of A-B-O incompatible transplant or T-cell cross-match positive transplant

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
Everolimus (RAD001)	Drug	Low dose tacrolimus, Very low dose tacrolimus
Tacrolimus	Drug	Low dose tacrolimus, Very low dose tacrolimus
Basiliximab	Drug	Low dose tacrolimus, Very low dose tacrolimus
Corticosteroids	Drug	Low dose tacrolimus, Very low dose tacrolimus

Primary outcome

Renal Function Assessed by Calculated Glomerular Filtration Rate (cGFR)
Time frame: 12 months post -transplant
Renal function was assessed by calculated glomerular filtration rate (cGFR) using Modification of Diet in Renal Disease (MDRD)formula. GFR [mL/min/1.73m^2] = 186.3*(C-1.154)*(A-0.203)*G*R, where: * C is the serum concentration of creatinine [mg/dL], * A is patient age at sample collection date [years], * G=0.742 when gender is female, otherwise G=1, * R=1.21 when race is black, otherwise R=1

2 secondary outcomes

Number of Participants With Incidence of Biopsy-proven Acute Rejection (BPAR)
Time frame: from Month 4 through to Month 12
Percentage of Participants With Efficacy Failure
Time frame: Month 12

Results and safety

Results posted to the registry on 19 Jan 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Very Low Dose Tacrolimus	109	82
Low Dose Tacrolimus	119	95

Primary outcome: Renal Function Assessed by Calculated Glomerular Filtration Rate (cGFR)

Time frame: 12 months post -transplant. Mean (Standard Deviation). Unit: mL/min/1.73m^2

Measure	Very Low Dose Tacrolimus n = 92	Low Dose Tacrolimus n = 105
Value	57.07 (19.467)	51.73 (19.995)

Population analysed: Modified Intent-to-treat (ITT) population i.e patients with an available cGFR at month 12.

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Very Low Dose Tacrolimus	64 of 109 (58.7%)	103 of 109 (94.5%)	Not reported
Low Dose Tacrolimus	61 of 119 (51.3%)	114 of 119 (95.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22471345Langer RM, Hene R, Vitko S, Christiaans M, Tedesco-Silva H Jr, Ciechanowski K, Cassuto E, Rostaing L, Vilatoba M, Machein U, Ulbricht B, Junge G, Dong G, Pascual J. Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multicentre trial in renal transplantation. Transpl Int. 2012 May;25(5):592-602. doi: 10.1111/j.1432-2277.2012.01465.x. Epub 2012 Mar 26.

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Bioimpedance and Multiparametric Ultrasound-Guided Fluid Management After Kidney Transplantation
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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 study director

Novartis

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Everolimus (RAD001), Tacrolimus and Basiliximab in people with Renal Transplantation, run by Novartis at 1 site in Switzerland.

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 7 inclusion and 20 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 3 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. 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 19 Jan 2011). 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?

Renal Function Assessed by Calculated Glomerular Filtration Rate (cGFR) (time frame: 12 months post -transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00369161, which also lists 1 linked publication.

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 3 Mar 2017.