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Kidney TransplantPhase 3NCT01025817

Non-inferiority Study of Safety and Efficacy of Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in Kidney Transplant Recipients

A Phase 3 study testing Everolimus and tacrolimus and mycophenolate mofetil and tacrolimus in people with Kidney Transplant, run by Novartis Pharmaceuticals at 50 sites in 2 countries.

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

The purpose of this phase 3b study is to compare the safety and efficacy of everolimus with low dose tacrolimus to mycophenolate mofetil with standard dose tacrolimus in kidney transplant recipients. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Kidney Transplant
What is being tested?
Everolimus and tacrolimus and mycophenolate mofetil and tacrolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
613 participants
Where
50 sitesin 2 countries
Study dates
Jan 2010to Mar 2013
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female renal recipients 18-70 years of age undergoing kidney transplantation, either primary or re-transplant;
  • Recipient of a cadaveric, deceased donor (including expanded criteria donor organs and deceased donor organs after cardiac death), living unrelated or non-HLA identical living related donor kidney;
  • Graft must be functional (producing greater than or equal to 100 ml of urine within 24 hours after transplantation) at time of randomization.

Who cannot join

  • Donor organ with a cold ischemic time > 30 hours;
  • Males or females who produce less than 100 ml of urine in the first 24 hours post-transplantation;
  • Males or females who are recipients of ABO incompatible transplants, or T cell, or B cell crossmatch positive transplant;
  • Males or females with severe total hypercholesterolemia or total hypertriglyceridemia (Patients on lipid lowering treatment with controlled hyperlipidemia are acceptable);
  • Males or females who have any surgical or any medical condition, such as severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus, which in the opinion of the investigator, might alter the absorption, distribution, metabolism and/or excretion of study medication.
  • Other protocol related inclusion/exclusion criteria may apply.

Trial locations and contacts

50 sites in 2 countries.

50 sites in 2 countries

United States48 sites

  • Novartis Investigative Site

    Ann Arbor, Michigan, 48109-0331

  • Novartis Investigative Site

    Aurora, Colorado, 80045

  • Novartis Investigative Site

    Baltimore, Maryland, 21201

  • Novartis Investigative Site

    Birmingham, Alabama, 35233

  • Novartis Investigative Site

    Boston, Massachusetts, 02111

  • Novartis Investigative Site

    Buffalo, New York, 14215

  • Novartis Investigative Site

    Burlington, Vermont, 05401

  • Novartis Investigative Site

    Charleston, South Carolina, 29425

  • Novartis Investigative Site

    Charlottesville, Virginia, 22908

  • Novartis Investigative Site

    Chicago, Illinois, 60612

  • Novartis Investigative Site

    Chicago, Illinois, 60637

  • Novartis Investigative Site

    Dallas, Texas, 75246

  • Novartis Investigative Site

    Detroit, Michigan, 48202-2689

  • Novartis Investigative Site

    Detroit, Michigan, 48236

  • Novartis Investigative Site

    Durham, North Carolina, 27710

  • Novartis Investigative Site

    Fort Worth, Texas, 76104

  • Novartis Investigative Site

    Galveston, Texas, 77555-0144

  • Novartis Investigative Site

    Greenville, North Carolina, 27834

  • Novartis Investigative Site

    Harrisburg, Pennsylvania, 17105-8700

  • Novartis Investigative Site

    Houston, Texas, 77030

  • Novartis Investigative Site

    Livingston, New Jersey, 07039

  • Novartis Investigative Site

    Los Angeles, California, 90033

  • Novartis Investigative Site

    Los Angeles, California, 90048

  • Novartis Investigative Site

    Los Angeles, California, 90095

  • Novartis Investigative Site

    Lubbock, Texas, 79430

  • Novartis Investigative Site

    Miami, Florida, 33136

  • Novartis Investigative Site

    Minneapolis, Minnesota, 55455

  • Novartis Investigative Site

    Nashville, Tennessee, 37212-3139

  • Novartis Investigative Site

    New York, New York, 10032

  • Novartis Investigative Site

    Norfolk, Virginia, 23507

  • Novartis Investigative Site

    Omaha, Nebraska, 68198-3285

  • Novartis Investigative Site

    Orange, California, 92868

  • Novartis Investigative Site

    Orlando, Florida, 32804

  • Novartis Investigative Site

    Portland, Oregon, 97239

  • Novartis Investigative Site

    Richmond, Virginia, 23298

  • Novartis Investigative Site

    Royal Oak, Michigan, 48073

  • Novartis Investigative Site

    Sacramento, California, 95817

  • Novartis Investigative Site

    Salt Lake City, Utah, 84132

  • Novartis Investigative Site

    San Diego, California, 92103

  • Novartis Investigative Site

    San Diego, California, 92123

  • Novartis Investigative Site

    San Francisco, California, 94115

  • Novartis Investigative Site

    San Francisco, California, 94143-0780

  • Novartis Investigative Site

    Seattle, Washington, 98195

  • Novartis Investigative Site

    Spokane, Washington, 99204

  • Novartis Investigative Site

    St Louis, Missouri, 63110

  • Novartis Investigative Site

    Tampa, Florida, 33606

  • Novartis Investigative Site

    Tucson, Arizona, 85742-5022

  • Novartis Investigative Site

    Worcester, Massachusetts, 01655

Other trials in United States

Canada2 sites

  • Novartis Investigative Site

    Montreal, Quebec, H1T 2M4

  • Novartis Investigative Site

    Montreal, Quebec, H2L 4M1

Other trials in Canada

About this study

Official title: A 12 Month, Multi-center, Randomized, Open-label Non-inferiority Study Comparing Safety and Efficacy of Concentration-controlled Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in de Novo Renal Transplant Recipients

The purpose of this phase 3b study is to compare the safety and efficacy of everolimus with low dose tacrolimus to mycophenolate mofetil with standard dose tacrolimus in kidney transplant recipients.

Being tested
Everolimus and tacrolimus, mycophenolate mofetil and tacrolimus
Keywords
Kidney transplant, renal transplant, immunosuppression, mycophenolate mofetil, tacrolimus, everolimus

What participants receive

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

  • Everolimus and tacrolimusDrug

    Everolimus:

    • Dosage form: 0.75 mg, 0.25 mg, and 0.5 mg tablets
    • Dose: 1.5 mg per day
    • Frequency: 0.75 mg twice daily

    Tacrolimus:

    • Dose adjusted to maintain specific blood levels

  • mycophenolate mofetil and tacrolimusDrug

    Also called Active Comparator Control)

    Mycophenolate mofetil: - Dose form: 250 mg capsule - Dose: 2g per day - Frequency: 1g twice daily Tacrolimus: - Dose adjusted to maintain specific blood levels

Study groups in NCT01025817
Study groupRoleWhat they receive
Everolimus (EVR) & low dose of tacrolimusExperimentalEverolimus (EVR) and tacrolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was < 3 ng/mL, or reduced if the trough level was > 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
Receives: Drug: Everolimus and tacrolimus
Mycophenolate mofetil & standard dose tacrolimusActive comparatorMycophenolate mofetil and tacrolimus (MMF) treatment arm: MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. Tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, target level of tacrolimus was reduced to 5 - 8 ng/mL.
Receives: Drug: mycophenolate mofetil and tacrolimus

What is being measured

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

  1. Number of Participants With Incidence of Composite Efficacy Failure

    Efficacy failure rate used the composite endpoint of: (1) treated biopsy-proven acute rejection (BPAR)*, (2) graft loss, (3) participant death or(4) loss to follow-up. *A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis.

    Measured: 12 Months

Secondary outcomes (6)

  1. Estimated Glomerular Filtration Rate (eGFR)

    Renal function was assessed by estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. MDRD formula: GFR [mL/min/1.73m˄2] = 186.3*(C˄-1.154)*(A˄-0.203)*G*R. DEFINITIONS: C = serum concentration of creatinine [mg/dL]; A = age [years]; G = 0.742 when gender is female, otherwise G = 1; R = 1.21 when race is black, otherwise R = 1

    Measured: 12 Months

  2. Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease)

    Participants with incidence of CMV (viremia, syndrome and disease). CMV is cytomegalovirus.

    Measured: 12 Months

  3. Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy

    Participants with Incidence of BKV (viremia, viruria, or nephropathy). BKV is Polyomavirus type BK.

    Measured: 12 Months

  4. Number of Participants With Incidence of New Onset of Diabetes Mellitus

    Incidence of new onset diabetes mellitus defined as non-diabetic patients before transplantation, who are receiving glucose lowering treatment for more than 30 days post-transplant, or with a random plasma glucose ≥200 mg dL (11.1 mmol/L) with 2 fasting plasma glucose values ≥126 mg/dL (7 mmol/L)

    Measured: 12 Months

  5. Number of Participants With Incidence of Proteinuria Events

    Number of participants with Incidence of proteinuria events indicating chronic kidney disease

    Measured: Baseline and 12 Months

  6. Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events

    Incidence of adverse events, serious adverse events, and tacrolimus-associated adverse events by System Organ Class

    Measured: 12 Months

Timeline

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

  1. First posted4 Dec 2009 (estimated)
  2. Study startJan 2010
  3. Primary completionMar 2013
  4. Study completionMar 2013

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
613 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01025817
Sponsor's protocol ID
CRAD001AUS92
Status last verified
Oct 2015
First submitted
19 Nov 2009
Last updated
11 Nov 2015
Data monitoring committee
Yes

Publications

  • Shihab F, Qazi Y, Mulgaonkar S, McCague K, Patel D, Peddi VR, Shaffer D. Association of Clinical Events With Everolimus Exposure in Kidney Transplant Patients Receiving Low Doses of Tacrolimus. Am J Transplant. 2017 Sep;17(9):2363-2371. doi: 10.1111/ajt.14215. Epub 2017 Mar 4.

    PubMed 28141897

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Everolimus and tacrolimus and mycophenolate mofetil and tacrolimus in people with Kidney Transplant, run by Novartis Pharmaceuticals at 50 sites in 2 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 6 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 11 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in United States, Canada. 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 6 Jun 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?

Number of Participants With Incidence of Composite Efficacy Failure (time frame: 12 Months). 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 NCT01025817, 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 11 Nov 2015.

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