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

Kidney Transplant Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01025817
• Other study ID #: CRAD001AUS92
• Status: Completed
• Phase: Phase 3
• First received: November 19, 2009
• Last updated: October 13, 2015
• Start date: January 2010
• Est. completion date: March 2013

Study information

• Verified date: October 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 613
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Other protocol related inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplant

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Buffalo	New York
United States	Novartis Investigative Site	Burlington	Vermont
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Charlottesville	Virginia
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	Fort Worth	Texas
United States	Novartis Investigative Site	Galveston	Texas
United States	Novartis Investigative Site	Greenville	North Carolina
United States	Novartis Investigative Site	Harrisburg	Pennsylvania
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Livingston	New Jersey
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Lubbock	Texas
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Norfolk	Virginia
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Orange	California
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Royal Oak	Michigan
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	San Francisco	California
United States	Novartis Investigative Site	San Francisco	California
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Spokane	Washington
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 Months	No
Secondary	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	12 Months	No
Secondary	Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease)	Participants with incidence of CMV (viremia, syndrome and disease). CMV is cytomegalovirus.	12 Months	Yes
Secondary	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.	12 Months	Yes
Secondary	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)	12 Months	No
Secondary	Number of Participants With Incidence of Proteinuria Events	Number of participants with Incidence of proteinuria events indicating chronic kidney disease	Baseline and 12 Months	No
Secondary	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	12 Months	Yes