Trial Outcomes & Findings for A Pilot Study Comparing the Safety and Efficacy of Everolimus With Other Medicines in Recipients of ECD/DCD Kidneys (NCT NCT01878786)

Last Updated: 2019-04-26

Results Overview

The primary objective of this study is to evaluate concentration-controlled everolimus and low dose tacrolimus compared to MMF/MPA with standard dose tacrolimus at 24 months post-transplant with respect to the composite efficacy failure rates (treated biopsy proven acute rejection episodes (BPAR), graft loss, death, loss to follow-up) in de novo renal transplant recipients.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

25 participants

Primary outcome timeframe

24 months

Results posted on

2019-04-26

Participant Flow

Participant milestones

Participant milestones
Measure	ERL & TAC Concentration controlled everolimus(ERL) \& Low dose tacrolimus(TAC) + corticosteroid withdraw Everolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus . Tacrolimus: CNI	ERL & TAC --> MMF/MPA Concentration controlled everolimus \& low dose tacrolimus --\> mycophenolate mofetil (MMF) at Month 3 + corticosteroid withdraw Everolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus . Tacrolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus.	Standard Dose TAC + MMF/MPA Standard dose of tacrolimus + mycophenolate mofetil + corticosteroid withdraw Tacrolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus. Mycophenolate mofetil (MMF/MPA): Control Drug
Overall Study STARTED	9	9	7
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	9	9	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

24 patients were between 18 and 65, one patient 65

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ERL & TAC n=9 Participants Concentration controlled everolimus(ERL) \& Low dose tacrolimus(TAC) + corticosteroid withdraw Everolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus . Tacrolimus: CNI	ERL & TAC --> MMF/MPA n=9 Participants Concentration controlled everolimus \& low dose tacrolimus --\> mycophenolate mofetil (MMF) at Month 3 + corticosteroid withdraw Everolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus . Tacrolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus.	Standard Dose TAC + MMF/MPA n=7 Participants Standard dose of tacrolimus + mycophenolate mofetil + corticosteroid withdraw Tacrolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus. Mycophenolate mofetil (MMF/MPA): Control Drug	Total n=25 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants • 24 patients were between 18 and 65, one patient 65	0 Participants n=7 Participants • 24 patients were between 18 and 65, one patient 65	0 Participants n=5 Participants • 24 patients were between 18 and 65, one patient 65	0 Participants n=4 Participants • 24 patients were between 18 and 65, one patient 65
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants • 24 patients were between 18 and 65, one patient 65	9 Participants n=7 Participants • 24 patients were between 18 and 65, one patient 65	6 Participants n=5 Participants • 24 patients were between 18 and 65, one patient 65	24 Participants n=4 Participants • 24 patients were between 18 and 65, one patient 65
Age, Categorical >=65 years	0 Participants n=5 Participants • 24 patients were between 18 and 65, one patient 65	0 Participants n=7 Participants • 24 patients were between 18 and 65, one patient 65	1 Participants n=5 Participants • 24 patients were between 18 and 65, one patient 65	1 Participants n=4 Participants • 24 patients were between 18 and 65, one patient 65
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	17 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	23 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	21 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	9 participants n=5 Participants	9 participants n=7 Participants	7 participants n=5 Participants	25 participants n=4 Participants

PRIMARY outcome

Timeframe: 24 months

Population: Study was terminated prematurely. There was no data analysis performed on the incomplete data set.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 months

Population: Study was terminated prematurely. There was no data analysis performed on the incomplete data set.

The key secondary objective is to compare renal function of the everolimus treatment arms to the MMF/MPA treatment arm at 12 and 24 months post-transplantation. Renal function will be measured by the calculated glomerular filtration rate (GFR), using the MDRD (Modification of Diet in Renal Disease) formula (20).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Study was terminated prematurely. There was no data analysis performed on the incomplete data set.

Outcome measures

Outcome data not reported

Adverse Events

ERL & TAC

Serious events: 7 serious events

Other events: 8 other events

Deaths: 0 deaths

ERL & TAC --> MMF/MPA

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Standard Dose TAC + MMF/MPA

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ERL & TAC n=9 participants at risk Concentration controlled everolimus(ERL) \& Low dose tacrolimus(TAC) + corticosteroid withdraw Everolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus . Tacrolimus: CNI	ERL & TAC --> MMF/MPA n=9 participants at risk Concentration controlled everolimus \& low dose tacrolimus --\> mycophenolate mofetil (MMF) at Month 3 + corticosteroid withdraw Everolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus . Tacrolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus.	Standard Dose TAC + MMF/MPA n=7 participants at risk Standard dose of tacrolimus + mycophenolate mofetil + corticosteroid withdraw Tacrolimus: One of the immunosuppressants currently being evaluated to replace CNIs in patients with CNI nephropathy is the mammalian Target of Rapamycin (mTOR) inhibitor, Sirolimus. Everolimus is a derivative of Sirolimus and belongs to this class of immunosuppressants, therefore, both drugs have similar side effect profile. The half-life of Everolimus is almost half of Sirolimus (Everolimus 30 hours vs Sirolimus 62 hours), which makes its dose adjustment easier although it would require more frequent dosing. In clinical trials, Everolimus has demonstrated its potential role as a safe alternative in minimizing and/or eliminating CNI such as Cyclosporin A and Tacrolimus. Mycophenolate mofetil (MMF/MPA): Control Drug
Infections and infestations Sepsis and Multiple Organ Failure	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.
Gastrointestinal disorders Constipation	11.1% 1/9 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/7 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.
Surgical and medical procedures GI Surgery	11.1% 1/9 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/7 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.
Renal and urinary disorders Left Renal Mass/Nephrectomy	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	11.1% 1/9 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/7 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.
General disorders Neck and Facial Edema	11.1% 1/9 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/7 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.
Surgical and medical procedures Admission	11.1% 1/9 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/7 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.
Blood and lymphatic system disorders ER Admission for Blood Transfusion	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.
Renal and urinary disorders UTI	11.1% 1/9 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/7 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.
Renal and urinary disorders Hydronephrosis (Possible malrotation of kidney, possible uretropelvic junction obstruction)	11.1% 1/9 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/7 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.
Respiratory, thoracic and mediastinal disorders Fluid Overload and Chest Pressure	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	11.1% 1/9 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/7 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.
Surgical and medical procedures Wound Dehiscence	11.1% 1/9 • Number of events 1 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/9 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.	0.00% 0/7 • Adverse events were recorded from the time of study drug through the end of the study. The study was terminated prematurely.

Other adverse events

Additional Information

Dr. Matthew Cooper

MedStar Georgetown Transplant Institute

Phone: 202-444-0753

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place