Study Evaluating The Use Of Sirolimus In Recipients Of Kidney Allografts From Expanded Criteria Donors (ECD)

Study Overview
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Brief Summary
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The purpose of this observational study is to examine the clinical outcomes of the use of sirolimus as base therapy in kidney allograft recipients from Expanded Criteria Donors (ECD) under conditions of routine clinical practice. The primary objective is to identify the current criteria/reasons to use sirolimus as base therapy in this selected population and define and understand the emerging patterns of immunosuppressive treatment with sirolimus.

Detailed Description
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pilot study

Official Title
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Surveillance Registry Of Sirolimus Use In Recipients Of Kidney Allograft From Expanded Criteria Donors (ECD)

Conditions
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Renal Transplantation

Intervention / Treatment
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* Drug: Sirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 years or older. Patients who received a renal transplant (primary, secondary, tertiary, etc.) without pancreas, from Expanded Criteria Donors (ECD), 3 months prior and no later than 1 year at the time of study enrollment. Patients who provided informed consent. Patients without sirolimus as base therapy. Exclusion Criteria: Patients who are unwilling or unable to provide informed consent or who lack a legal guardian or designee able to provide consent on their behalf. Patients who are unable to complete the study. Patients who are participating in another clinical trial during the last 6 months. Pregnant or lactating patients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| A<br> | Drug: Sirolimus<br>* Non interventional. Sirolimus administered by Principal Investigator per standard practice and labeling.<br>* Other names: Rapamune;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Main Reason for the Use of Sirolimus (Rapamune) Therapy | The study employ a questionnaire which included different clinical criteria to determine the main medical reason for the introduction of sirolimus (Rapamune) therapy after renal transplant. The physician responsible selected the one that was considered the main reason for introduction of sirolimus (Rapamune) as base immunosuppressive therapy. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of Graft Survival | Graft survival was considered in participants who did not experience graft failure. Graft failure was determined by return to dialysis for a period of at least 12 weeks with no return of function, or graft loss whichever occurred sooner. | Month 12 | 
| Probability of no Acute Rejection | Diagnosis of acute rejection was made via kidney biopsy. Categorization of biopsies with suspected acute rejection was based on histological findings using updated 1997 Banff criteria: Grade 1A: significant interstitial infiltration (greater than [>] 25 percent [%] of parenchyma affected) and foci of moderate tubulitis (5-10 cells/tubular cross section), Grade 1B: significant interstitial infiltration (>25% of parenchyma affected) and severe tubulitis (>10 mononuclear cells/tubular cross section), Grade 2A: mild-moderate intimal arteritis, Grade 2B: severe intimal arteritis comprising >25% of the luminal area and Grade 3: transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells. Probability of no acute rejection throughout the sirolimus (Rapamune) therapy was estimated using Kaplan-Meier method. | Month 12 | 
| Probability of Participant Survival | Participant's survival defined as participant living with or without a functioning graft. Probability of participant survival throughout the sirolimus (Rapamune) therapy was estimated using Kaplan-Meier method. | Month 12 | 
| Average Dose of Immunosuppressive Drugs Administered | Immunosuppressive drugs administered included cyclosporin A (CsA) administration based on monitoring of plasma trough levels (C0), CsA administration based on monitoring of plasma levels 2-hours after CsA dose (C2), tacrolimus, and sirolimus (Rapamune). | Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 | 
| Average Blood Level of Immunosuppressive Drugs Administered | Immunosuppressive drugs administered included cyclosporin A (CsA) administration based on monitoring of plasma trough levels (C0), CsA administration based on monitoring of plasma levels 2-hours after CsA dose (C2), tacrolimus, and sirolimus (Rapamune). | Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 | 
| Average Creatinine Clearance | Creatinine clearance (CCr) is a measure of glomerular filtration rate (GMFR), an index of kidney function. CCr is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliter per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function. | Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 | 
| Average Proteinuria | Proteinuria defined as the presence of an excess of serum proteins in the urine. Normal value of proteinuria is below 0.15 grams per 24 hours (g/24 hr). | Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 | 
| Percentage of Participants Who Prematurely Discontinued the Sirolimus (Rapamune) Therapy |  | Baseline up to Month 12 | 
| Percentage of Participants Who Prematurely Discontinued the Sirolimus (Rapamune) Therapy Due to Inefficacy |  | Baseline up to Month 12 | 
| Percentage of Participants Who Prematurely Discontinued the Sirolimus (Rapamune) Therapy Due to Adverse Events | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Participants who discontinued sirolimus (Rapamune) therapy prematurely due to AE were obliged to discontinue sirolimus (Rapamune) therapy permanently, are reported. | Baseline up to Month 12 | 
| Body Mass Index | BMI was calculated as weight divided by height squared and measured as kilogram per square meter (kg/m^2). | Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 | 
| Number of Participants With Body Temperature | Body temperature was measured in degree Celsius. Each participants were classified into three different categories based on their body temperature: body temperature less than 35 degree Celsius = hypothermia, body temperature between 35 to 37.5 degree Celsius = feverless, and body temperature greater than 37.5 degree Celsius = fever. | Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 | 
| Blood Pressure | Systolic and diastolic blood pressure (BP) was measured after the participant had rested in the supine position for at least 5 minutes with the participant's arm supported at the level of the heart, and recorded to the nearest millimeters of mercury (mmHg). | Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 | 
| Pulse Rate |  | Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 | 
| Body Weight |  | Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53 | 
| Percentage of Participants With Physical Abnormalities | Physical abnormalities included all the abnormalities related to general disorders and administration site conditions, gastrointestinal disorders, skin and subcutaneous tissue disorders, vascular disorders, investigations, infections and infestations, eye disorders, respiratory, thoracic and mediastinal disorders, nervous system disorders, musculoskeletal and connective tissue disorders, injury, poisoning and procedural complications, surgical and medical procedures, psychiatric disorders, neoplasms benign, malignant and unspecified (incl cysts and polyps), ear and labyrinth disorders, and congenital, familial and genetic disorders. | Baseline up to Month 12 | 
| Percentage of Participants With Adverse Events | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. | Baseline up to Month 12 | 
| Percentage of Participants With Serious Adverse Events | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Baseline up to Month 12 | 
| Percentage of Participants With Clinically-Significant Electrocardiogram Abnormalities | Standard 12-lead ECG was performed. ECG intervals included PR interval (time between the onset of atrial depolarization and the onset of ventricular depolarization), QRS interval (represented ventricular depolarization), QT interval (time corresponding to the beginning of depolarization to repolarization of the ventricles) corrected using Fridericia's formula (QTcF = QT divided by cube root of RR interval) and heart rate (time interval between consecutive heart beats [RR interval]). | Baseline up to Month 12 | 
| Percentage of Participants With Clinically-Significant Radiological Abnormalities | Radiological examination was performed to evaluate presence or signs of infections or pneumonitis. | Baseline up to Month 12 |