Progression of Renal Interstitial Fibrosis / Tubular Atro... | NCT01079143

ID	Type	Description	Link
2009-011473-33	EudraCT Number

Label	Type	Description	Intervention Names
Certican EMT+	Experimental	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.	Drug: Certican® Drug: Myfortic Drug: Simulect® Drug: Corticosteroids
Certican EMT-	Experimental	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.	Drug: Certican® Drug: Myfortic Drug: Simulect® Drug: Corticosteroids
Neoral EMT+	Active Comparator	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.	Drug: Neoral Drug: Myfortic Drug: Simulect® Drug: Corticosteroids
Neoral EMT-	Active Comparator	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.

Name	Type	Description	Arm Group Labels	Other Names
Certican®	Drug	Certican® was supplied to the participating centers by Novartis for the whole duration of the study in the form of tablets containing 0.75, 0.5 and 0.25 mg and packaged in blister packs.

Measure	Description	Time Frame
Number of Participants With Progression of Renal Graft Fibrosis (Primary Comparison - ITT Population	Progression of Interstitial Fibrosis/Tabular Atrophy (IF/TA) is the percentage (%) of participants with an increase >= 1 in IF/TA grade according to Banff (2005 - 2007)according to Epithelial-mesenchymal transition (EMT) profile and by treatment groups. Grade I (the better): mild interstitial fibrosis and tubular atrophy (<25% of cortical area) Grade II : moderate interstitial fibrosis and tubular atrophy (26-50% of cortical area) Grade III (the worse) : severe interstitial fibrosis and tubular atrophy (>50% of cortical area)	Month 3 (M3) and Month 12 (M12) post transplantation

Measure	Description	Time Frame
Interstitial Fibrosis/Tabular Atrophy (IF/TA)	Incidence and severity of IF/TA according to 2005/2007 Banff classification system grades (grades l to lll). IF/TA grade was assessed during centralized reading according to the Banff 2005/2007 classification comprising grade I (<25%), grade II (25-50%) and grade III (>50% of lesions).	M3 and M12 post transplantation

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Recipient of a primary or secondary deceased or living (related or not) donor kidney transplant and who requires basiliximab induction therapy.
Cold ischemia time < 30 hours.
Women of child-bearing age, even those with a history of infertility, must have had a negative pregnancy test during the 7 days before screening or at the time of screening, and must use a recognized and reliable method of contraception throughout the study and for 2 months after discontinuing the study treatment.
Patients who want and are able to take part in the entire study, and have given their written consent.
Patients who are registered with a French national health insurance scheme or are covered by such a scheme.

Exclusion Criteria:

Recipient of multi-organ transplantation, including dual kidneys, or who have previously received non renal transplant organ.
Patients receiving a graft from a non-heart-beating donor.
Anti-HLA antibody levels ≥ 20% in the last 3 months before the inclusion.
ABO incompatible graft or with positive cross match T.
Severe hyperlipidemia: total cholesterol ≥ 9.1 mmol/L (≥ 350 mg/dL) and/or triglycerides ≥ 8.5 mmol/L (≥ 750 mg/dL) despite appropriate lipid-lowering therapy.
Known hypersensitivity or contraindications to mycophenolic acid, cyclosporine or lactose.
Known hypersensitivity or contraindications to macrolides or drugs of the mTOR inhibitor class.
HIV seropositive, or active chronic hepatitis B (HBs Ab) or C. Results obtained during the 6 months before the inclusion are accepted. Recipients from donors with hepatitis B or C will be excluded.
Patients with thrombocytopenia (≤ 75000/mm3), absolute neutrophil count (≤ 1500/mm3), leukocytopenia (≤ 2500/mm3) and/or hemoglobin < 8g/dL at the inclusion visit.
ASAT, ALAT or total bilirubin ≥ 3 UNL.
Uncontrolled severe infection, severe allergy requiring an acute or chronic treatment.
Patients with a malignant disease or previous malignancy in the past 5 years, with the exception of excised basal cell or squamous cell carcinoma and in situ cervical cancer treated.
Medical or surgical condition, with the exception of the transplantation, which in the investigator's opinion could exclude the patient.
Women who are pregnant, breastfeeding or of reproductive age and refuse or are unable to use a recognized and reliable method of contraception.
Patients with symptoms of significant mental or somatic disease. Inability to cooperate or communicate with the investigator.
Patients under supervision or guardianship or any patient subject to legal protection

Randomization criteria:

Eligibility criteria (no later than 4 months post-transplantation:

Renal graft biopsy performed at M3 and adequate histological material sent within the deadline for the determination of EMT.
Woman of child-bearing potential, even in case of a history of infertility, must use a recognized and reliable method of contraception throughout the study and for 2 months after discontinuing the study treatment.

Non-eligibility criteria (no later than 4 months post-transplantation):

Acute rejection histologically proven between transplantation and randomization (local reading).
Acute subclinical rejection diagnosed on the M3 biopsy (except borderline lesions) (local reading).
Positive anti-donor antibodies at M3.
Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 (MDRDa).
Proteinuria ≥ 1 g/24h.
Severe hyperlipidemia: total cholesterol ≥ 9.1 mmol/L (≥ 350 mg/dL) and/or triglycerides ≥ 8.5 mmol/L (≥ 750 mg/dL) despite appropriate lipid-lowering therapy.
Thrombocytopenia (≤ 75000/mm3), absolute neutrophil count (≤ 1500/mm3), leukocytopenia (≤ 2500/mm3) and/or hemoglobin < 8 g/dL.
ASAT, ALAT or total bilirubin ≥ 3 UNL.
Medical or surgical condition which in the investigator's opinion might exclude the patient.

Other protocol-defined inclusion/exclusion criteria may apply.

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Caen	Cedex	14033	France
Novartis Investigative Site

PubMed Identifier	Type	Citation	Retractions
31530561	Derived	Loupy A, Aubert O, Orandi BJ, Naesens M, Bouatou Y, Raynaud M, Divard G, Jackson AM, Viglietti D, Giral M, Kamar N, Thaunat O, Morelon E, Delahousse M, Kuypers D, Hertig A, Rondeau E, Bailly E, Eskandary F, Bohmig G, Gupta G, Glotz D, Legendre C, Montgomery RA, Stegall MD, Empana JP, Jouven X, Segev DL, Lefaucheur C. Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study. BMJ. 2019 Sep 17;366:l4923. doi: 10.1136/bmj.l4923.

ID	Title	Description
FG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Progression of Renal Graft Fibrosis (Primary Comparison - ITT Population

Progression of Interstitial Fibrosis/Tabular Atrophy (IF/TA) is the percentage (%) of participants with an increase >= 1 in IF/TA grade according to Banff (2005 - 2007)according to Epithelial-mesenchymal transition (EMT) profile and by treatment groups.

Grade I (the better): mild interstitial fibrosis and tubular atrophy (<25% of cortical area) Grade II : moderate interstitial fibrosis and tubular atrophy (26-50% of cortical area) Grade III (the worse) : severe interstitial fibrosis and tubular atrophy (>50% of cortical area)

ITT population: All patients randomized in the study who received at least one dose of the study treatment. Among the 194 participants in the ITT group, 58 patients in the EMT+ group completed the study providing a graft biopsy for analysis at M3 and M12. The primary comparison concerned only the Certican and the Neoral EMT+ groups.

Posted

Number

Participants

Month 3 (M3) and Month 12 (M12) post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Neoral EMT+	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.

Units	Counts
Participants	OG00026 OG00132

Title

Denominators

Categories

Participants with an IF/TA grade <= II at M3

Title	Measurements
	OG00026 OG00131

Participants with Fibrosis progression, M3 to M12

Title	Measurements
	OG000

Secondary

Interstitial Fibrosis/Tabular Atrophy (IF/TA)

Incidence and severity of IF/TA according to 2005/2007 Banff classification system grades (grades l to lll). IF/TA grade was assessed during centralized reading according to the Banff 2005/2007 classification comprising grade I (<25%), grade II (25-50%) and grade III (>50% of lesions).

Posted

Number

Number of participants

M3 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG002	Neoral EMT+

Secondary

Change in Interstitial Fibrosis/Tabular Atrophy (IF/TA) Grade

Difference (M12 - M3) in IF/TA grade. IF/TA grade was assessed during centralized reading according to the Banff 2005/2007 classification comprising grade I (<25%), grade II (25-50%) and grade III (>50% of lesions).

Posted

Number

Number of Participants

M3 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG002	Neoral EMT+

Secondary

Risk Factors of IF/TA Progression

Composite factors regarding fibrosis progression at 12 months using a logistic regression model; the parameters initially considered concerned the demographic characteristics of both recipient and donor, transplantation characteristics, hypertension, diabetes, study treatments, immunosuppression, EMT, IF/TA, function at M3, the onset of acute rejection, the presence of anti-donor antibodies at M12, infections and BK virus viremia.

Arteriolar hyaline thickening is thickening of the walls of arterioles by the deposition of homogeneous pink hyaline material.

BPAR is biopsy proven acute rejection. TEM progression is the increase ≥ 1 of TEM score between Month 3 and Month 12

Posted

Number

Participants

M12 post transplantation

ID	Title	Description
OG000	Yes- Fibrosis Progression	Participants who experienced fibrosis progression based on IF/TA (univariate analysis)
OG001	No- No Fibrosis Progression	Participants who did not experience fibrosis progression based on IF/TA (univariate analysis)

Secondary

Change in Percentage of Interstitial Fibrosis (IF) by Numerical Quantification

Percentage of IF measured by numerical quantification. The IF percentage was transposed in grade according to the following rule: grade 0 for an IF % ≤5%, grade I for an IF % ranging from >5% to < 25%, grade II for an IF % ranging from 25 to 50%, grade III for an IF % >50%. Interstitial graft fibrosis has been identified as the primary cause of graft loss following death with a functional graft [3-5].

Posted

Mean

Standard Deviation

Percentage of IF

M3 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.

Secondary

Number of Participants With Progression of Renal Fibrosis Using Numerical Quantification

Comparisons according to epithelial-mesenchymal transition (EMT) profile and immunosuppressive treatment

Posted

Number

Participants

M3 to M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG002	Neoral EMT+	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.

Secondary

Number of Participants With Epithelial-mesenchymal Transition (EMT) Status

Incidence and severity of EMT status. EMT status was determined centrally using the graft biopsy taken at 3 months. The result was quickly obtained (within 7 to 15 days) and sent to the company in charge of randomization in order to allocate each patient to a treatment group and to provide the investigator with this information without confirming EMT status.

Posted

Number

Participants

M3 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.

Secondary

Number of Participants With Epithelial-mesenchymal Transition (EMT) Score

Incidence and severity of EMT score. The intensity of EMT markers expression present and detectable in the renal graft at an early stage following transplantation is known as EMT score.

EMT score 0 (the best): <1 EMT score 1 (the better): 1-10% of tubular atrophy EMT score 2: 10-25% of tubular atrophy EMT score 3: 25-50% of tubular atrophy EMT score 4 (the worst): >50% of tubular atrophy

Posted

Number

participants

M3 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.

Secondary

Change in EMT Score

Change (M12 - M3) in EMT Score. Progression in EMT score is defined as an increase by >=1 of EMT score from M3 to M12.

EMT score 0 (the best): <1 EMT score 1 (the better) : 1-10% of tubular atrophy EMT score 2 : 10-25% of tubular atrophy EMT score 3 : 25-50% of tubular atrophy EMT score 4 (the worst): >50% of tubular atrophy

Posted

Mean

Standard Deviation

scores on a scale

M3 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG002

Secondary

Incidence (Number) of Subclinical Rejections and Borderline Lesions

Incidence of subclinical rejections and borderline lesions with regards to histological evidence of rejection with clinical findings.

Subclinical rejections: rejection without clinical symptoms which is diagnosed by chance when a graft biopsy is performed.

Clinically suspected BPAR: rejection suspected because of the presence of clinical symptoms (fever, pain, increase of creatinine) and then confirmed by the graft biopsy.

Borderline lesions: suspicious for acute T-cell mediated rejection. This category is used when no intimal arteritis is present, but there are foci of tubulitis with minor interstitial infiltration or interstitial infiltration with mild tubulitis.

ITT population: All patients randomized in the study who received at least one dose of the study treatment.

Posted

Number

Participants

ID	Title	Description
OG000	Certican	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Neoral	Between transplantation adn randomization, all patients have received Neoral. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic.

Secondary

Change From Baseline (M3) in Estimated Glomerular Filtration Rate (eGFR)

eGFR was calculated according to the abbreviated Modification of Diet in Renal Disease (MDRD) Formula and creatinine clearance according to the Cockcroft-Gault formula (mL/min/1.73m²).

LOCF = Last observation carried forward

ITT population: All patients randomized in the study who received at least one dose of the study treatment.

Posted

Least Squares Mean

Standard Error

mL/min/1.73m^2

M3 (baseline) to M12 post transplantation

ID	Title	Description
OG000	Certican	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Neoral	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.

Units	Counts
Participants

Secondary

Change in Estimated Glomerular Filtration Rate (eGFR) at M12 From Baseline (M3) - ANCOVA Model

The average patient renal function was evaluated on the basis of eGFR was calculated according to the abbreviated MDRD formula and creatinine clearance according to the Cockcroft-Gault formula (mL/min/1.73m²).

ITT population: All patients randomized in the study who received at least one dose of the study treatment.

Posted

Mean

Standard Deviation

mL/min/1.73m²

Baseline (M3), M12

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG002	Neoral EMT+	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.

Secondary

Change in Urine Protein/Creatinine Ratio (Without Imputation)

One of the factors associated with EMT progression between M3 and M12 according to univariate analysis (ITT biopsies M3 & M12).

ITT population: All patients randomized in the study who received at least one dose of the study treatment.

Posted

Mean

Standard Deviation

mg/mmol

Month 3 (baseline), Month 12

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG002	Neoral EMT+	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.

Secondary

Treatment Failures

A treatment failure is defined as biopsy proven acute rejection (BPAR), a graft loss, a death or a loss to follow up. It was assessed between randomization and 6 and 12 months post-transplantation.

ITT population: All patients randomized in the study who received at least one dose of the study treatment.

Posted

Number

Number of Participants

M6 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG002	Neoral EMT+	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.

Secondary

Type of Biopsy Proven Acute Rejection (BPAR)

A biopsy proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB or III as per 2005/2007 Banff histological classification system.

Biopsy graded IA: Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells).

Biopsy grade IB: Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells).

Biopsy grade IIA: Mild to moderate intimal arteritis. Biopsy graded IIB: Severe intimal arteritis comprising > 25% of the lumenal area.

Biopsy graded III: Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation).

ITT population: All patients randomized in the study who received at least one dose of the study treatment.

Posted

Number

Participants

M6 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.

Secondary

Severity of BPAR

A biopsy proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB or III as per 2005/2007 Banff histological classification system.

Biopsy graded IA: Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells).

Biopsy grade IB: Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells).

Biopsy grade IIA: Mild to moderate intimal arteritis. Biopsy graded IIB: Severe intimal arteritis comprising > 25% of the lumenal area.

Biopsy graded III: Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation).

ITT population: All patients randomized in the study who received at least one dose of the study treatment.

Posted

Number

Participants

M6 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.

Secondary

Incidence (Number) of BPAR

A biopsy proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB or III as per 2005/2007 Banff histological classification system.

ITT population: All patients randomized in the study who received at least one dose of the study treatment.

Posted

Number

Number of participants

M6 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG002	Neoral EMT+	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.

Secondary

Incidence (Number) of Participants With Graft Losses

If a participant underwent a graft nephrectomy, then the day of nephrectomy was considered as the day of graft loss.

ITT population: All patients randomized in the study who received at least one dose of the study treatment.

Posted

Number

Participants

M6 and M12 post transplantation

ID	Title	Description
OG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
OG002	Neoral EMT+	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Agranulocytosis	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0012 affected96 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected98 at risk EG0010 affected96 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected98 at risk EG0010 affected96 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Aphthous stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0012 affected96 at risk
Colitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0012 affected96 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Dental necrosis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected98 at risk EG0013 affected96 at risk
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Hernial eventration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Oesophageal ulcer	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Periodontitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0011 affected96 at risk
Chills	General disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
General physical health deterioration	General disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Hyperthermia	General disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0011 affected96 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0005 affected98 at risk EG0015 affected96 at risk
Sudden death	General disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Hepatitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Amyloidosis	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Kidney transplant rejection	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0014 affected96 at risk
Transplant rejection	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Abdominal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Bacillus infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Bacterial pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected98 at risk EG0012 affected96 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0012 affected96 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Diarrhoea infectious	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0012 affected96 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Escherichia infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Eye infection toxoplasmal	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Gastroenteritis yersinia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Hepatic cyst infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Lung infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Orchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Pneumocystis jiroveci pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Polyomavirus-associated nephropathy	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Pseudomonal sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected98 at risk EG0013 affected96 at risk
Pyelonephritis acute	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0013 affected96 at risk
Renal cyst infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Staphylococcal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Transplant abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected98 at risk EG0014 affected96 at risk
Viral pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Arteriovenous fistula site complication	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Arteriovenous fistula thrombosis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0002 affected98 at risk EG0010 affected96 at risk
Graft loss	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0011 affected96 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0012 affected96 at risk
Post procedural haematuria	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Ureteric anastomosis complication	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Vascular graft complication	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0003 affected98 at risk EG0012 affected96 at risk
Blood pressure increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0012 affected96 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Gout	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Hypercreatininaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0011 affected96 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Fistula	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Multiple myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Status epilepticus	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0011 affected96 at risk
Neurosis	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Glomerulonephritis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Haematuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Proteinuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0011 affected96 at risk
Renal failure acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0004 affected98 at risk EG0012 affected96 at risk
Renal tubular disorder	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Renal tubular necrosis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Vesicoureteric reflux	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Metrorrhagia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0012 affected96 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0011 affected96 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0012 affected96 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Capillaritis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Hip arthroplasty	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Haematoma	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Haemorrhage	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Iliac artery stenosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Orthostatic hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Phlebitis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected98 at risk EG0011 affected96 at risk
Subclavian artery stenosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk
Venous thrombosis limb	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected98 at risk EG0010 affected96 at risk

ID	Term
D000068338	Everolimus
D016572	Cyclosporine
D009173	Mycophenolic Acid
D000077552	Basiliximab
D000305	Adrenal Cortex Hormones

ID	Term
D020123	Sirolimus
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D003524	Cyclosporins
D010456	Peptides, Cyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D002208	Caproates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D005227	Fatty Acids
D008055	Lipids
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D012712	Serum Globulins
D005916	Globulins
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

ID	Title	Description
BG000	Certican EMT+	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
BG001	Certican EMT-	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
BG002	Neoral EMT+	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
BG003	Neoral EMT-	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Neoral	Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.			39	98	59	98
EG001	Certican	Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.			46	96	59	96