Trial Outcomes & Findings for Evaluation of Calcineurin-inhibitor Reduction With Conversion at 2 Months to Everolimus/Reduced Tacrolimus in Renal Transplant Recipients Following Campath® Induction (NCT NCT01935128)
NCT ID: NCT01935128
Last Updated: 2022-05-26
Results Overview
Renal function in patients will be assessed using glomerular filtration rate (GFR) as measured by the Modified Diet Renal Disease (MDRD) estimation. Glomerular filtration is the process by which the kidneys filter the blood, removing excess wastes and fluids. Glomerular filtration rate (GFR) is a calculation that determines how well the blood is filtered by the kidneys, which is one way to measure remaining kidney function. GFR is also used to find the stage of chronic kidney disease. Glomerular filtration rate is usually calculated using a mathematical formula that compares a person's size, age, sex, and race to serum creatinine levels. The higher the GFR number, the better the kidney function; the lower the GFR number, the worse the kidney function. A GFR of 60 or higher is in the normal range. A GFR below 60 may mean kidney disease. A GFR of 15 or lower may mean kidney failure.
COMPLETED
PHASE4
55 participants
2 years
2022-05-26
Participant Flow
Participants were recruited following renal transplantation at a single transplant center. Participants were recruited between 2 and 6 months post-transplant. Date of first enrollment was July 3, 2013 and date of last enrollment was July 6, 2018.
50 participants met the inclusion/exclusion criteria and were enrolled in the treatment arm.
Participant milestones
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Overall Study
STARTED
|
50
|
|
Overall Study
COMPLETED
|
43
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Overall Study
Death
|
1
|
|
Overall Study
Adverse Event
|
6
|
Baseline Characteristics
Evaluation of Calcineurin-inhibitor Reduction With Conversion at 2 Months to Everolimus/Reduced Tacrolimus in Renal Transplant Recipients Following Campath® Induction
Baseline characteristics by cohort
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
37 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=5 Participants
|
|
Age, Continuous
|
51.74 years
STANDARD_DEVIATION 12.62 • n=5 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
41 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
50 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: Intent to treat population (all participants assigned to treatment arm). Last observation carried forward (LOCF) imputation method
Renal function in patients will be assessed using glomerular filtration rate (GFR) as measured by the Modified Diet Renal Disease (MDRD) estimation. Glomerular filtration is the process by which the kidneys filter the blood, removing excess wastes and fluids. Glomerular filtration rate (GFR) is a calculation that determines how well the blood is filtered by the kidneys, which is one way to measure remaining kidney function. GFR is also used to find the stage of chronic kidney disease. Glomerular filtration rate is usually calculated using a mathematical formula that compares a person's size, age, sex, and race to serum creatinine levels. The higher the GFR number, the better the kidney function; the lower the GFR number, the worse the kidney function. A GFR of 60 or higher is in the normal range. A GFR below 60 may mean kidney disease. A GFR of 15 or lower may mean kidney failure.
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Renal Function
|
65.70 mL/min/1.73 m2
Standard Deviation 20.04
|
PRIMARY outcome
Timeframe: 2 yearsGraft survival is defined as the percentage of kidney transplants still functioning at 2 years post baseline visit . One patient died of natural causes at 12 months with a functioning graft.
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Graft Survival
|
49 Participants
|
PRIMARY outcome
Timeframe: 2 yearsThe percentage of patients with a treated biopsy-proven acute rejection (a co-primary endpoint) within the 2 year study time period
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Biopsy Proven Acute Rejection
|
1 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPatient survival is defined as the percentage of patients still surviving at 2 years post baseline visit
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Patient Survival
|
49 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with impaired glucose tolerance as indicated by fasting blood glucose levels, Hemoglobin A1C (HgbA1C) levels and the need for hypoglycemic medications
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Impaired Glucose Tolerance
|
14 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with proteinuria as defined by spot urine protein to creatinine ratio greater than 1.0
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Proteinuria
|
7 Participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The overall number of participants analyzed was 50. This population was split into participants who were negative for hyperlipidemia at baseline and developed new onset hyperlipidemia (10) identified in Row 1 and participants who were baseline positive for hyperlipidemia but who required a new lipid-lowering medication or an increase in the dose of their lipid-lowering medication over the course of the study (40) as identified in Row 2.
The number of patients with hyperlipidemia as defined by the development of new onset hyperlipidemia in the baseline negative patients and the number of baseline positive patients who required starting a new lipid-lowering medication or an increase in dose of their lipid-lowering medication over the course of the study
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Lipid Levels
Baseline negative patients with new onset hyperlipidemia
|
7 Participants
|
|
Lipid Levels
Baseline positive patients started on new lipid-lowering medication or needing increase in dose
|
19 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with stomatitis/aphthous ulcer
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Mouth Ulcers
|
14 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with gastrointestinal complaints as indicated by abdominal pain, nausea, vomiting or diarrhea not accounted for by a specific episode of illness such as gastroenteritis
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Gastrointestinal Complaints
|
22 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with leukopenia as indicated by white blood cell count less than 1.0, absolute neutrophil count less than 500 or the need for exogenous granulocyte stimulating factor administration
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Leukopenia
|
1 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with thrombocytopenia as defined by platelet count less than 50
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Thrombocytopenia
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with neurotoxicity as evidenced by incidence of new onset seizure activity or tremors
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Neurotoxicity
|
1 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with pneumonitis as demonstrated by lung inflammation symptoms such as shortness of breath and/or cough requiring clinical intervention and management
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Pneumonitis
|
3 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with Incidence of cytomegalovirus infection as defined by need for hospitalization
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Cytomegalovirus
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with serious infections as defined by need for hospitalization
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Infection Requiring Hospitalization
|
11 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with BK infection as defined by blood titers requiring reduction in immunosuppressive dose
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
BK Infection
|
7 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with BK nephropathy as defined by biopsy. Note that biopsies were not required as part of the study but were only done as part of the patient's standard of care if rejection was suspected (i.e. if the serum creatinine increased by 25% and was not associated with elevated tacrolimus levels or clinical signs of dehydration/illness to account for elevated creatinine)
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
BK Nephropathy
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients developing malignancies including post-transplant lymphoproliferative disorders
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Malignancies
|
2 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with cardiovascular complications as indicated by conditions such as dysrhythmias, coronary artery disease requiring intervention or myocardial infarction
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Cardiovascular Complications
|
1 Participants
|
SECONDARY outcome
Timeframe: 2 yearsThe number of patients with incidence of development of donor specific antibody
Outcome measures
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 Participants
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Development of Donor Specific Antibody
|
2 Participants
|
Adverse Events
Arm 1 Everolimus/Reduced Dose Tacrolimus
Serious adverse events
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 participants at risk
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Vascular disorders
Venous thrombosis
|
8.0%
4/50 • Number of events 4 • 2 years
|
|
General disorders
Pyrexia
|
8.0%
4/50 • Number of events 5 • 2 years
|
|
Infections and infestations
Influenza A
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Infections and infestations
Gastroenteritis
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
2.0%
1/50 • Number of events 2 • 2 years
|
|
Infections and infestations
Endocarditis
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Infections and infestations
Urosepsis
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Infections and infestations
Urinary tract infection
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Renal and urinary disorders
Acute kidney injury
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Psychiatric disorders
Depression suicidal
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Injury, poisoning and procedural complications
Vascular pseudoaneurysm
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Immune system disorders
Kidney transplant rejection
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Infections and infestations
Nasal abscess
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Surgical and medical procedures
Parathyroid gland excision
|
2.0%
1/50 • Number of events 1 • 2 years
|
|
Surgical and medical procedures
Nephrectomy
|
4.0%
2/50 • Number of events 2 • 2 years
|
Other adverse events
| Measure |
Arm 1 Everolimus/Reduced Dose Tacrolimus
n=50 participants at risk
In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.
Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention
|
|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
62.0%
31/50 • Number of events 52 • 2 years
|
|
Infections and infestations
Urinary tract infection
|
18.0%
9/50 • Number of events 19 • 2 years
|
|
Skin and subcutaneous tissue disorders
Fungal skin infection
|
8.0%
4/50 • Number of events 5 • 2 years
|
|
Metabolism and nutrition disorders
Hyperlipidemia
|
28.0%
14/50 • Number of events 14 • 2 years
|
|
Metabolism and nutrition disorders
Worsening hyperlipidemia
|
36.0%
18/50 • Number of events 20 • 2 years
|
|
Gastrointestinal disorders
Nausea
|
18.0%
9/50 • Number of events 9 • 2 years
|
|
Gastrointestinal disorders
Vomiting
|
16.0%
8/50 • Number of events 8 • 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
36.0%
18/50 • Number of events 25 • 2 years
|
|
Gastrointestinal disorders
Abdominal pain
|
16.0%
8/50 • Number of events 8 • 2 years
|
|
Gastrointestinal disorders
Abdominal distention
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Gastrointestinal disorders
Stomach upset
|
14.0%
7/50 • Number of events 7 • 2 years
|
|
Gastrointestinal disorders
Gastroenteritis
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Investigations
Weight gain
|
50.0%
25/50 • Number of events 33 • 2 years
|
|
Investigations
Weight loss
|
22.0%
11/50 • Number of events 12 • 2 years
|
|
Infections and infestations
Herpes zoster
|
10.0%
5/50 • Number of events 5 • 2 years
|
|
Hepatobiliary disorders
Hepatic enzyme increased
|
26.0%
13/50 • Number of events 14 • 2 years
|
|
Gastrointestinal disorders
Stomatitis
|
28.0%
14/50 • Number of events 18 • 2 years
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Metabolism and nutrition disorders
Worsening diabetes mellitus
|
8.0%
4/50 • Number of events 4 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
28.0%
14/50 • Number of events 16 • 2 years
|
|
Infections and infestations
Cellulitis
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Skin and subcutaneous tissue disorders
Rash, acneiform
|
14.0%
7/50 • Number of events 8 • 2 years
|
|
Skin and subcutaneous tissue disorders
Worsening rash, acneiform
|
6.0%
3/50 • Number of events 4 • 2 years
|
|
Skin and subcutaneous tissue disorders
Rash, generalized
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Psychiatric disorders
Depression
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Psychiatric disorders
Worsening depression
|
4.0%
2/50 • Number of events 2 • 2 years
|
|
General disorders
Edema, limb
|
46.0%
23/50 • Number of events 30 • 2 years
|
|
General disorders
Fatigue
|
24.0%
12/50 • Number of events 14 • 2 years
|
|
General disorders
Worsening fatigue
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Renal and urinary disorders
Blood creatinine increased
|
16.0%
8/50 • Number of events 9 • 2 years
|
|
Blood and lymphatic system disorders
Erythrocytosis
|
16.0%
8/50 • Number of events 8 • 2 years
|
|
General disorders
Pyrexia
|
18.0%
9/50 • Number of events 9 • 2 years
|
|
Nervous system disorders
Dizziness
|
8.0%
4/50 • Number of events 4 • 2 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
6.0%
3/50 • Number of events 4 • 2 years
|
|
Psychiatric disorders
Mental concentration difficulty
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Renal and urinary disorders
Proteinuria
|
22.0%
11/50 • Number of events 12 • 2 years
|
|
Renal and urinary disorders
Worsening proteinuria
|
14.0%
7/50 • Number of events 8 • 2 years
|
|
General disorders
Chills
|
14.0%
7/50 • Number of events 9 • 2 years
|
|
Eye disorders
Visual acuity reduced
|
8.0%
4/50 • Number of events 4 • 2 years
|
|
General disorders
Generalized body aches
|
8.0%
4/50 • Number of events 4 • 2 years
|
|
Blood and lymphatic system disorders
Leukopenia
|
18.0%
9/50 • Number of events 12 • 2 years
|
|
Blood and lymphatic system disorders
Worsening leukopenia
|
4.0%
2/50 • Number of events 3 • 2 years
|
|
Renal and urinary disorders
Hyponatremia
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
4.0%
2/50 • Number of events 3 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Low back pain
|
8.0%
4/50 • Number of events 5 • 2 years
|
|
Psychiatric disorders
Insomnia
|
10.0%
5/50 • Number of events 5 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Chest pain
|
4.0%
2/50 • Number of events 2 • 2 years
|
|
Metabolism and nutrition disorders
Excessive thirst
|
6.0%
3/50 • Number of events 5 • 2 years
|
|
Renal and urinary disorders
Hematuria
|
14.0%
7/50 • Number of events 7 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
4.0%
2/50 • Number of events 2 • 2 years
|
|
Investigations
BK viremia
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Immune system disorders
Donor specific antibody positive
|
4.0%
2/50 • Number of events 2 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
16.0%
8/50 • Number of events 10 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
12.0%
6/50 • Number of events 7 • 2 years
|
|
Vascular disorders
Hypertension
|
20.0%
10/50 • Number of events 13 • 2 years
|
|
Vascular disorders
Worsening hypertension
|
18.0%
9/50 • Number of events 9 • 2 years
|
|
Nervous system disorders
Headache
|
16.0%
8/50 • Number of events 11 • 2 years
|
|
Nervous system disorders
Worsening headache
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.0%
4/50 • Number of events 4 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea exertional
|
6.0%
3/50 • Number of events 3 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Worsening dyspnea
|
6.0%
3/50 • Number of events 3 • 2 years
|
Additional Information
Michael A. Rees, MD, PhD
University of Toledo Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place