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

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.

Time frame: Baseline

Population: Intention-to-Treat (ITT) population included all participants who were treated with Rapamune for at least 4 or 5 weeks.

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).

Time frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53

Population: ITT population. N(number of participants analyzed)=participants evaluable for this measure. n=participants evaluable at given time point for specified immunosuppressive. Results not reported for CsA C0 at Week 1/2, 12/13, 24/25; CsA C2 at Week 1/2, 4/5, 12/13, 24/25, 52/53; sirolimus at baseline as no participants evaluable at those time points.

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.

Time frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53

Population: ITT population included all participants who were treated with Rapamune for at least 4 or 5 weeks. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluable for this measure at given time points.

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).

Time frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53

Population: ITT population. N(number of participants analyzed)=participants evaluable for this measure. n=participants evaluable at given time point for specified immunosuppressive. Results not reported for CsA C0 at Week 1/2, 12/13, 24/25; CsA C2 at Week 1/2, 4/5, 12/13, 24/25, 52/53; sirolimus at baseline as no participants evaluable at those time points.

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).

Time frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53

Population: ITT population included all participants who were treated with Rapamune for at least 4 or 5 weeks. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluable for this measure at given time points.

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).

Time frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53

Population: Safety population included all participants who had received at least 1 dose of Rapamune and were subsequently interrogated. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluable for this measure at given time points.

BMI was calculated as weight divided by height squared and measured as kilogram per square meter (kg/m\^2).

Time frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53

Population: Safety population included all participants who had received at least 1 dose of Rapamune and were subsequently interrogated. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluable for this measure at given time points.

Time frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53

Population: Safety population included all participants who had received at least 1 dose of Rapamune and were subsequently interrogated. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluable for this measure at given time points.

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.

Time frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53

Population: Safety population. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluable for this measure at given time points. Results for hypothermia not reported as none of the participants was found hypothermic.

Time frame: Baseline up to Month 12

Population: ITT population included all participants who were treated with Rapamune for at least 4 or 5 weeks.

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.

Time frame: Baseline up to Month 12

Population: ITT population included all participants who were treated with Rapamune for at least 4 or 5 weeks.

Time frame: Baseline up to Month 12

Population: ITT population included all participants who were treated with Rapamune for at least 4 or 5 weeks.

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.

Time frame: Baseline up to Month 12

Population: Safety population included all participants who had received at least 1 dose of Rapamune and were subsequently interrogated.

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 \[RR interval\]).

Time frame: Baseline up to Month 12

Population: Safety population included all participants who had received at least 1 dose of Rapamune and were subsequently interrogated.

Radiological examination was performed to evaluate presence or signs of infections or pneumonitis.

Time frame: Baseline up to Month 12

Population: Safety population included all participants who had received at least 1 dose of Rapamune and were subsequently interrogated.

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.

Time frame: Baseline up to Month 12

Population: Safety population included all participants who had received at least 1 dose of Rapamune and were subsequently interrogated.

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.

Time frame: Baseline up to Month 12

Population: Safety population included all participants who had received at least 1 dose of Rapamune and were subsequently interrogated.

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.

Time frame: Month 12

Population: ITT population included all participants who were treated with Rapamune for at least 4 or 5 weeks.

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.

Time frame: Month 12

Population: ITT population included all participants who were treated with Rapamune for at least 4 or 5 weeks.

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.

Time frame: Month 12

Population: ITT population included all participants who were treated with Rapamune for at least 4 or 5 weeks.

Time frame: Baseline, Week 1 or 2, 4 or 5, 12 or 13, 24 or 25, 52 or 53

Population: Safety population included all participants who had received at least 1 dose of Rapamune and were subsequently interrogated. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluable for this measure at given time points.