Trial Outcomes & Findings for Comparison of the Efficacy and Safety of Sirolimus Versus Everolimus Versus Mycophenolate in Kidney Transplantation (NCT NCT03468478)

NCT ID: NCT03468478

Last Updated: 2023-04-24

Results Overview

Incidence of CMV infection/disease in three study groups (SRL, EVR anda MPS).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

1209 participants

Primary outcome timeframe

12 months follow up

Results posted on

2023-04-24

Participant Flow

Participant milestones

Participant milestones
Measure	Sirolimus +Tacrolimus Patients will receive initial dose of 0,05 mg/kg BID oftacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of sirolimus of 3mg once a day to reach blood trough concentration between 4-8 ng/mL. Sirolimus: sirolimus combined to reduced dose of tacrolimus	Everolimus +Tacrolimus Patients will receive initial dose of 0,05 mg/kg BID de tacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of 1.5 mg BID of everolimus to reach blood trough concentration between 4-8 ng/mL. Everolimus: everolimus combined to reduced dose of tacrolimus	Mycophenolate +Tacrolimus Patients will receive initial dose of 0,1 mg/kg BID de tacrolimusto reach blood trough concentration between Fixed dose of mycophenolate (mycophenolate mofetil, 1 g BID or sodium mycophenolate, 720 mg BID). Mycophenolic acid: Control arm: mycophenolate combined to regular tacrolimus
Overall Study STARTED	403	403	403
Overall Study COMPLETED	86	90	90
Overall Study NOT COMPLETED	317	313	313

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of the Efficacy and Safety of Sirolimus Versus Everolimus Versus Mycophenolate in Kidney Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sirolimus +Tacrolimus n=86 Participants Patients will receive initial dose of 0,05 mg/kg BID oftacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of sirolimus of 3mg once a day to reach blood trough concentration between 4-8 ng/mL. Sirolimus: sirolimus combined to reduced dose of tacrolimus	Everolimus +Tacrolimus n=90 Participants Patients will receive initial dose of 0,05 mg/kg BID de tacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of 1.5 mg BID of everolimus to reach blood trough concentration between 4-8 ng/mL. Everolimus: everolimus combined to reduced dose of tacrolimus	Mycophenolate +Tacrolimus n=90 Participants Patients will receive initial dose of 0,1 mg/kg BID de tacrolimusto reach blood trough concentration between Fixed dose of mycophenolate (mycophenolate mofetil, 1 g BID or sodium mycophenolate, 720 mg BID). Mycophenolic acid: Control arm: mycophenolate combined to regular tacrolimus	Total n=266 Participants Total of all reporting groups
Age, Continuous	43.35 years STANDARD_DEVIATION 12.4 • n=5 Participants	44.5 years STANDARD_DEVIATION 14.76 • n=7 Participants	44.15 years STANDARD_DEVIATION 12.32 • n=5 Participants	44.01 years STANDARD_DEVIATION 13.18 • n=4 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	29 Participants n=7 Participants	23 Participants n=5 Participants	74 Participants n=4 Participants
Sex: Female, Male Male	64 Participants n=5 Participants	61 Participants n=7 Participants	67 Participants n=5 Participants	192 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	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 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	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants	32 Participants n=4 Participants
Race (NIH/OMB) White	61 Participants n=5 Participants	56 Participants n=7 Participants	60 Participants n=5 Participants	177 Participants n=4 Participants
Race (NIH/OMB) More than one race	17 Participants n=5 Participants	25 Participants n=7 Participants	13 Participants n=5 Participants	55 Participants n=4 Participants
Race (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
Region of Enrollment Brazil	86 participants n=5 Participants	90 participants n=7 Participants	90 participants n=5 Participants	266 participants n=4 Participants

PRIMARY outcome

Timeframe: 12 months follow up

Incidence of CMV infection/disease in three study groups (SRL, EVR anda MPS).

Outcome measures

Outcome measures
Measure	Sirolimus +Tacrolimus n=86 Participants Patients will receive initial dose of 0,05 mg/kg BID oftacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of sirolimus of 3mg once a day to reach blood trough concentration between 4-8 ng/mL. Sirolimus: sirolimus combined to reduced dose of tacrolimus	Everolimus +Tacrolimus n=90 Participants Patients will receive initial dose of 0,05 mg/kg BID de tacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of 1.5 mg BID of everolimus to reach blood trough concentration between 4-8 ng/mL. Everolimus: everolimus combined to reduced dose of tacrolimus	Mycophenolate +Tacrolimus n=90 Participants Patients will receive initial dose of 0,1 mg/kg BID de tacrolimusto reach blood trough concentration between Fixed dose of mycophenolate (mycophenolate mofetil, 1 g BID or sodium mycophenolate, 720 mg BID). Mycophenolic acid: Control arm: mycophenolate combined to regular tacrolimus
Incidence of Cytomegalovirus Infection or Disease	9 Participants	7 Participants	39 Participants

Adverse Events

Sirolimus +Tacrolimus

Serious events: 43 serious events

Other events: 0 other events

Deaths: 2 deaths

Everolimus +Tacrolimus

Serious events: 47 serious events

Other events: 0 other events

Deaths: 1 deaths

Mycophenolate +Tacrolimus

Serious events: 71 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Sirolimus +Tacrolimus n=86 participants at risk Patients will receive initial dose of 0,05 mg/kg BID oftacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of sirolimus of 3mg once a day to reach blood trough concentration between 4-8 ng/mL. Sirolimus: sirolimus combined to reduced dose of tacrolimus	Everolimus +Tacrolimus n=90 participants at risk Patients will receive initial dose of 0,05 mg/kg BID de tacrolimus to reach blood trough concentration between 3-5 ng/mL. Initial dose of 1.5 mg BID of everolimus to reach blood trough concentration between 4-8 ng/mL. Everolimus: everolimus combined to reduced dose of tacrolimus	Mycophenolate +Tacrolimus n=90 participants at risk Patients will receive initial dose of 0,1 mg/kg BID de tacrolimusto reach blood trough concentration between Fixed dose of mycophenolate (mycophenolate mofetil, 1 g BID or sodium mycophenolate, 720 mg BID). Mycophenolic acid: Control arm: mycophenolate combined to regular tacrolimus
Infections and infestations CMV infection	5.8% 5/86 • Number of events 5 • 12 months Number of episodes of serious adverse events in each study group.	6.7% 6/90 • Number of events 6 • 12 months Number of episodes of serious adverse events in each study group.	26.7% 24/90 • Number of events 25 • 12 months Number of episodes of serious adverse events in each study group.
Skin and subcutaneous tissue disorders Dehiscence of the aponeurosis	1.2% 1/86 • Number of events 1 • 12 months Number of episodes of serious adverse events in each study group.	1.1% 1/90 • Number of events 1 • 12 months Number of episodes of serious adverse events in each study group.	2.2% 2/90 • Number of events 2 • 12 months Number of episodes of serious adverse events in each study group.
Renal and urinary disorders Acute graft dysfunction	1.2% 1/86 • Number of events 1 • 12 months Number of episodes of serious adverse events in each study group.	2.2% 2/90 • Number of events 2 • 12 months Number of episodes of serious adverse events in each study group.	0.00% 0/90 • 12 months Number of episodes of serious adverse events in each study group.
Vascular disorders Renal artery stenosis	1.2% 1/86 • Number of events 1 • 12 months Number of episodes of serious adverse events in each study group.	1.1% 1/90 • Number of events 1 • 12 months Number of episodes of serious adverse events in each study group.	1.1% 1/90 • Number of events 1 • 12 months Number of episodes of serious adverse events in each study group.
Gastrointestinal disorders Acute gastroenterocolitis	0.00% 0/86 • 12 months Number of episodes of serious adverse events in each study group.	2.2% 2/90 • Number of events 2 • 12 months Number of episodes of serious adverse events in each study group.	3.3% 3/90 • Number of events 3 • 12 months Number of episodes of serious adverse events in each study group.
Renal and urinary disorders Pyelonephritis	4.7% 4/86 • Number of events 4 • 12 months Number of episodes of serious adverse events in each study group.	6.7% 6/90 • Number of events 6 • 12 months Number of episodes of serious adverse events in each study group.	5.6% 5/90 • Number of events 7 • 12 months Number of episodes of serious adverse events in each study group.
Renal and urinary disorders Acute graft rejection	8.1% 7/86 • Number of events 8 • 12 months Number of episodes of serious adverse events in each study group.	6.7% 6/90 • Number of events 6 • 12 months Number of episodes of serious adverse events in each study group.	5.6% 5/90 • Number of events 5 • 12 months Number of episodes of serious adverse events in each study group.
Respiratory, thoracic and mediastinal disorders Sepsis of pulmonary focus	0.00% 0/86 • 12 months Number of episodes of serious adverse events in each study group.	2.2% 2/90 • Number of events 3 • 12 months Number of episodes of serious adverse events in each study group.	0.00% 0/90 • 12 months Number of episodes of serious adverse events in each study group.
Vascular disorders Deep vein thrombosis	2.3% 2/86 • Number of events 2 • 12 months Number of episodes of serious adverse events in each study group.	1.1% 1/90 • Number of events 1 • 12 months Number of episodes of serious adverse events in each study group.	0.00% 0/90 • 12 months Number of episodes of serious adverse events in each study group.
Skin and subcutaneous tissue disorders Infection of the operative wound	2.3% 2/86 • Number of events 2 • 12 months Number of episodes of serious adverse events in each study group.	0.00% 0/90 • 12 months Number of episodes of serious adverse events in each study group.	2.2% 2/90 • Number of events 2 • 12 months Number of episodes of serious adverse events in each study group.
Respiratory, thoracic and mediastinal disorders Sars-Cov-2 infection	1.2% 1/86 • Number of events 1 • 12 months Number of episodes of serious adverse events in each study group.	1.1% 1/90 • Number of events 1 • 12 months Number of episodes of serious adverse events in each study group.	1.1% 1/90 • Number of events 1 • 12 months Number of episodes of serious adverse events in each study group.
General disorders Other	22.1% 19/86 • Number of events 19 • 12 months Number of episodes of serious adverse events in each study group.	21.1% 19/90 • Number of events 21 • 12 months Number of episodes of serious adverse events in each study group.	31.1% 28/90 • Number of events 30 • 12 months Number of episodes of serious adverse events in each study group.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Helio Tedesco Silva Junior

Hospital do Rim - Fundação Oswaldo Ramos

Phone: 55 11 50878113

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place