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

NCT ID: NCT01025817

Last Updated: 2015-11-11

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

613 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2013-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Kidney Transplant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Everolimus (EVR) & low dose of tacrolimus

Everolimus (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.

Group Type EXPERIMENTAL

Everolimus and tacrolimus

Intervention Type DRUG

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 & standard dose tacrolimus

Mycophenolate 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.

Group Type ACTIVE_COMPARATOR

mycophenolate mofetil and tacrolimus

Intervention Type DRUG

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

Interventions

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Everolimus and tacrolimus

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

Intervention Type DRUG

mycophenolate mofetil and tacrolimus

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

Intervention Type DRUG

Other Intervention Names

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Active Comparator Control)

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Birmingham, Alabama, United States

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Tucson, Arizona, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Orange, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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San Francisco, California, United States

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Aurora, Colorado, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Worcester, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Detroit, Michigan, United States

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Royal Oak, Michigan, United States

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Minneapolis, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Livingston, New Jersey, United States

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Buffalo, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Greenville, North Carolina, United States

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Portland, Oregon, United States

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Harrisburg, Pennsylvania, United States

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Charleston, South Carolina, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Galveston, Texas, United States

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Houston, Texas, United States

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Lubbock, Texas, United States

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Salt Lake City, Utah, United States

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Burlington, Vermont, United States

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Charlottesville, Virginia, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Countries

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United States Canada

References

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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.

Reference Type DERIVED
PMID: 28141897 (View on PubMed)

Other Identifiers

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CRAD001AUS92

Identifier Type: -

Identifier Source: org_study_id

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