4EVERLUNG: Efficacy Regarding Renal Function of Everolimus in Combination With Specific Standard Immunosuppressive Regimen Lung Transplant Recipients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01404325
• Collaborator: (none)
• Enrollment: 130
• Locations: 9
• Arms: 2
• Actual Duration (Months): 59.1
• Patients Per Site: 14.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This trial evaluated the efficacy of an everolimus-based quadruple low immunosuppressive regimen versus a standard immunosuppressive regimen concerning kidney function in lung transplant recipients.

Condition or Disease	Intervention/Treatment	Phase
Lung Transplantation	Drug: standard therapy; Drug: Everolimus	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 2-arm, Prospective, Randomized, Controlled, Open-label, 12 Month Phase III Trial to Evaluate the Efficacy Regarding Renal Function of Everolimus in Combination With a Centre Specific Standard Immunosuppressive Regimen Consisting of CNI, Purinantagonists and Steroids Versus a Standard Triple Immunosuppressive Regimen in Lung Transplant Recipients.
• Actual Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Jan 5, 2017
• Actual Study Completion Date: Jan 5, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Quadruple low level IS regimen quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	Drug: Everolimus; quadruple immunosuppressive regimen consisting of everolimus, CNI, MPA and steroids; Other Names: RAD001
Experimental: Centre specific triple IS regimen centre specific CNI-based triple drug immunosuppression (IS)	Drug: standard therapy; centre specific CNI-based triple drug immunosuppression

Outcome Measures

Primary Outcome Measures

1. Calculated Glomerular Filtration Rate (cGFR) According to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at 12 Months [Month 12]

   Calculated Glomerular Filtration Rate (cGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at 12 months The CKD-EPI equation, expressed as a single equation, is GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)^-1.209 × 0.993Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/ĸ or 1, and max indicates the maximum of Scr/κ or 1

Secondary Outcome Measures

1. Calculated Glomerular Filtration Rate (cGFR) According to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

   Calculated Glomerular Filtration Rate (cGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at Month 1, 3, 6, 9 and 12. The CKD-EPI equation, expressed as a single equation, is GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)^-1.209 × 0.993Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/ĸ or 1, and max indicates the maximum of Scr/κ or 1

2. Calculated Glomerular Filtration Rate (cGFR) According to Cystatin C-based Hoek's Formula at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

   Calculated Glomerular Filtration Rate (cGFR) according to Cystatin C-based Hoek's formula at Month 1, 3, 6, 9, 12

3. Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

   Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 1, 3, 6, 9, 12 cGFR (in mL/min/1.73 m2) = 186.3*(C-1.154)*(A-0.203)*G*R where C = the serum concentration of creatinine (mg/dL), A = age (years), G = 0.742 when gender is female, otherwise G = 1, R = 1.21 when race is black, otherwise R = 1.

4. Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

   Calculated Glomerular Filtration Rate (cGFR) according to Cockcroft-Gault at Month 1, 3, 6, 9, 12 For men: GFR=(140-Age) x Body weight (kg) / 72 x Serum Creatinine (mg/dl) For women: GFR=0.85 (140 -Age) x Body weight(kg)/ 72 x Serum Creatinine (mg/dl)

5. Incidence of Patients Experiencing a Decline in GFR of < 10, 10-15, 15-20, 20-25 and > 25 mL/Min From Baseline to Month 6 and 12. [Baseline, Month 6, Month 12]

   Incidence of patients experiencing a decline in GFR of < 10, 10-15, 15-20, 20-25 and > 25 mL/min from Baseline to Month 6 and 12calculated by the CKD-EPI method. Participants are counted in each decline level observed for that participant; this means participants may be counted in more than 1 decline level.

6. Incidence of Renal Replacement Therapy at Month 6 and Month 12 [Month 6, Month 12]

   Incidence of renal replacement therapy at Month 6 and Month 12: There were no incidences in either group where renal replacement therapy was required

7. Time to Renal Replacement Therapy at Month 6 and Month 12 [Month 6, Month 12]

   Time to renal replacement therapy at Month 6 and Month 12: There were no incidences in either group where renal replacement therapy was required

8. Incidence of Acute Rejection Episodes at Month 6 and Month 12 [Month 6, Month 12]

   Incidence of acute rejection episodes at Month 6 and Month 12. This table counts multiple occurrences of rejection in the same patient as different incidents. Every incident is associated with both an A and a B classification. Classification A: Acute Rejection Grade 0 - none, Grade 1-minimal, Grade 2- mild, Grade 3-moderate, Grade 4-Severe; Classification B: Airway Inflammation-Grade 0-none, Grade 1R-low grade, Grade 2R-high grade, Grade X-ungradeable

9. Incidence of Graft Loss/Re-transplantation at Month 6 and Month 12 [Month 6, Month 12]

   Incidence of graft loss/re-transplantation at Month 6 and Month 12

10. Incidence of Bronchiolitis Obliterans Syndrome (BOS) at Month 6 and Month 12 [Month 6, Month 12]

    Incidence of Bronchiolitis obliterans syndrome (BOS) at Month 6 and Month 12 BOS 0 is FEV1 > 90% of baseline and FEF25-75% > 75% of baseline; BOS 0-p is FEV1 81-90% of baseline and/or FEF25-75% ≤ 75% of baseline; BOS 1 is FEV1 66-80% of baseline; BOS 2 is FEV1 51-65% of baseline; BOS 3 is FEV1 ≤ 50% of baseline

11. Incidence of Death at Month 6 and Month 12 [Month 6, Month 12]

    Incidence of death at Month 6 and Month 12

12. Quality of Life (QoL, SF36) at Month 6 and Month 12 [Month 6, Month 12]

    Quality of Life (QoL, SF36) at Month 6 and Month 12 Scores can range from a minimum of 0 (maximum disability) to a maximum of 100 (no disability).

13. Exercise Capacity 6-Minute Walk Test(6MWT) at Month 6 and Month 12 [Month 6, Month 12]

    Exercise capacity (6MWT) at Month 6 and Month 12 Measured by the Borg Scale. THE BORG SCALE 0 is Nothing at all, 0.5 is Very, very slight (just noticeable); 1 is Very slight, 2 is Slight (light); 3 is Moderate; 4 is Somewhat severe; 5 is Severe (heavy), 7 is Very severe, 10 is Very, very severe (maximal)The higher the Borg score implies increased shortness of breath and/or increased fatigue.

14. Incidence of Treated Arterial Hypertension up to Month 12 [up to Month 12]

    Incidence of treated of arterial hypertension up to Month 12

15. Incidence of Diabetes Mellitus up to Month 12 [up to Month 12]

    Incidence of Diabetes Mellitus up to Month 12

16. Trough Levels of Everolimus at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

    Trough levels of everolimus at Month 1, 3, 6, 9, 12

17. Adherence to Target Ranges of Everolimus at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

    Adherence to target ranges of everolimus at Month 1, 3, 6, 9, 12

18. Trough Levels of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

    Trough levels of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12

19. Adherence to Target Ranges of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

    Adherence to target ranges of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12

20. Trough Levels of Tacrolimus at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

    Trough levels of Tacrolimus at Month 1, 3, 6, 9, 12

21. Adherence to Target Ranges of Tacrolimus at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

    Adherence to target ranges of Tacrolimus at Month 1, 3, 6, 9, 12

22. Incidence of Bacterial, Viral, and Fungal Infections at Month 12 [Month 12]

    Incidence of bacterial, viral, and fungal infections at Month 12

23. Triglyceride Levels at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

    Triglyceride levels at Month 1, 3, 6, 9, 12

24. Total Cholesterol Levels at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

    Total Cholesterol levels at Month 1, 3, 6, 9, 12

25. Low-Density Lipoprotein (LDL)Cholesterol Levels at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

    LDL Cholesterol levels at Month 1, 3, 6, 9, 12

26. High-Density Lipoprotein (HDL)Cholesterol Levels at Month 1, 3, 6, 9, 12 [Month 1, 3, 6, 9, 12]

    HDL Cholesterol levels at Month 1, 3, 6, 9, 12

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Adult recipients of de novo cadaveric lung transplants 3-18 months prior to enrollment

Exclusion criteria:

• Patients with thrombocytopenia (platelets <100,000/mm³), with an absolute neutrophil count of <1,500/mm³ or leucopenia (leucocytes <3000/mm³), with anemia with Hb < 8g/dl at time of screening

• Patients with uncontrolled hypercholesterolemia (> 350 mg/dL; > 9.1 mmol/L) or hypertriglyceridemia (> 750 mg/dL; > 8.5 mmol/L) at time of screening

• Patients with a history of malignancy of any organ system, treated or untreated, during the last five years, whether or not there is evidence of local recurrence or metastases, except squamous or basal cell carcinoma of the skin Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Berlin		Germany	10117
2	Novartis Investigative Site	Berlin		Germany	13353
3	Novartis Investigative Site	Essen		Germany	45147
4	Novartis Investigative Site	Freiburg		Germany	79106
5	Novartis Investigative Site	Hamburg		Germany	20246
6	Novartis Investigative Site	Hannover		Germany	30625
7	Novartis Investigative Site	Homburg		Germany	66421
8	Novartis Investigative Site	Leipzig		Germany	04103
9	Novartis Investigative Site	Muenchen		Germany	81377

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01404325
• Other Study ID Numbers: CRAD001ADE36; 2011-001539-21
• First Posted: Jul 28, 2011
• Last Update Posted: Mar 14, 2019
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Lung transplantation; everolimus; kidney function; renal function
• Additional relevant MeSH terms: Everolimus

Study Results

Participant Flow

Recruitment Details	232 patients who were de novo lung transplant recipients were planned for enrolling into the study. A total of 130 patients were actually randomized with 67 patients randomized to the quadruple low-level treatment arm and 63 patients randomized to the center-specific triple treatment arm.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Period Title: Overall Study
STARTED	67	63
COMPLETED	63	61
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen	Total
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)	Total of all reporting groups
Overall Participants	67	63	130
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.9 (9.5)	54.2 (9.2)	54.0 (9.3)
Sex: Female, Male (Count of Participants)
Female	27 40.3%	22 34.9%	49 37.7%
Male	40 59.7%	41 65.1%	81 62.3%

Outcome Measures

1. Primary Outcome

Title	Calculated Glomerular Filtration Rate (cGFR) According to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at 12 Months
Description	Calculated Glomerular Filtration Rate (cGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at 12 months The CKD-EPI equation, expressed as a single equation, is GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)^-1.209 × 0.993Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/ĸ or 1, and max indicates the maximum of Scr/κ or 1
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set multiple imputation (FAS MI) consisted of all patients as randomized that received at least 1 dose of study drug & had a valid baseline assessment of the primary efficacy variable. Missing values was dealt with by multiple imputation (MI)

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Least Squares Mean (95% Confidence Interval) [mL/min]	64.5 (16.3)	54.6 (14.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Quadruple Low Level IS Regimen, Centre Specific Triple IS Regimen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Calculated Glomerular Filtration Rate (cGFR) According to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at Month 1, 3, 6, 9, 12
Description	Calculated Glomerular Filtration Rate (cGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at Month 1, 3, 6, 9 and 12. The CKD-EPI equation, expressed as a single equation, is GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)^-1.209 × 0.993Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/ĸ or 1, and max indicates the maximum of Scr/κ or 1
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	73.5 (13.9)	67.1 (12.4)
Month 3	70.4 (13.3)	64.3 (12.7)
Month 6	69.2 (15.5)	63.1 (15.0)
Month 9	69.0 (16.3)	62.3 (14.8)
Month 12	68.3 (16.3)	61.2 (14.3)

3. Secondary Outcome

Title	Calculated Glomerular Filtration Rate (cGFR) According to Cystatin C-based Hoek's Formula at Month 1, 3, 6, 9, 12
Description	Calculated Glomerular Filtration Rate (cGFR) according to Cystatin C-based Hoek's formula at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	68.5 (14.6)	61.8 (12.8)
Month 3	65.7 (15.2)	60.3 (10.6)
Month 6	63.0 (15.1)	58.7 (12.2)
Month 9	61.8 (14.1)	57.7 (12.8)
Month 12	60.8 (14.2)	57.5 (14.1)

4. Secondary Outcome

Title	Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 1, 3, 6, 9, 12
Description	Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 1, 3, 6, 9, 12 cGFR (in mL/min/1.73 m2) = 186.3*(C-1.154)*(A-0.203)*G*R where C = the serum concentration of creatinine (mg/dL), A = age (years), G = 0.742 when gender is female, otherwise G = 1, R = 1.21 when race is black, otherwise R = 1.
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	72.0 (13.5)	65.8 (11.8)
Month 3	68.7 (12.2)	63.3 (12.3)
Month 6	67.6 (14.1)	62.3 (15.0)
Month 9	67.4 (14.9)	61.7 (15.1)
Month 12	67.0 (14.8)	60.5 (14.4)

5. Secondary Outcome

Title	Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 1, 3, 6, 9, 12
Description	Calculated Glomerular Filtration Rate (cGFR) according to Cockcroft-Gault at Month 1, 3, 6, 9, 12 For men: GFR=(140-Age) x Body weight (kg) / 72 x Serum Creatinine (mg/dl) For women: GFR=0.85 (140 -Age) x Body weight(kg)/ 72 x Serum Creatinine (mg/dl)
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	78.6 (19.2)	72.1 (14.9)
Month 3	76.1 (17.6)	70.1 (16.0)
Month 6	76.2 (19.3)	69.1 (17.5)
Month 9	76.2 (20.1)	69.0 (18.2)
Month 12	76.2 (20.6)	68.4 (17.8)

6. Secondary Outcome

Title	Incidence of Patients Experiencing a Decline in GFR of < 10, 10-15, 15-20, 20-25 and > 25 mL/Min From Baseline to Month 6 and 12.
Description	Incidence of patients experiencing a decline in GFR of < 10, 10-15, 15-20, 20-25 and > 25 mL/min from Baseline to Month 6 and 12calculated by the CKD-EPI method. Participants are counted in each decline level observed for that participant; this means participants may be counted in more than 1 decline level.
Time Frame	Baseline, Month 6, Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Up to Month 6: < 10 mL/min	28	44
Up to Month 6: 10 - < 15 mL/min	9	18
Up to Month 6: 15 - < 20 mL/min	6	11
Up to Month 6: 20 - < 25 mL/min	2	7
Up to Month 6: > 25 mL/min	3	7
Up to Month 12: < 10 mL/min	36	53
Up to Month 12: 10 - < 15 mL/min	10	27
Up to Month 12: 15 - < 20 mL/min	8	18
Up to Month 12: 20 - < 25 mL/min	8	9
Up to Month 12: > 25 mL/min	7	9

7. Secondary Outcome

Title	Incidence of Renal Replacement Therapy at Month 6 and Month 12
Description	Incidence of renal replacement therapy at Month 6 and Month 12: There were no incidences in either group where renal replacement therapy was required
Time Frame	Month 6, Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
up to Month 6	0	0
up to Month 12	0	0

8. Secondary Outcome

Title	Time to Renal Replacement Therapy at Month 6 and Month 12
Description	Time to renal replacement therapy at Month 6 and Month 12: There were no incidences in either group where renal replacement therapy was required
Time Frame	Month 6, Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. The outcome could not be analyzed because there were no incidences of renal replacement therapy

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	0	0

9. Secondary Outcome

Title	Incidence of Acute Rejection Episodes at Month 6 and Month 12
Description	Incidence of acute rejection episodes at Month 6 and Month 12. This table counts multiple occurrences of rejection in the same patient as different incidents. Every incident is associated with both an A and a B classification. Classification A: Acute Rejection Grade 0 - none, Grade 1-minimal, Grade 2- mild, Grade 3-moderate, Grade 4-Severe; Classification B: Airway Inflammation-Grade 0-none, Grade 1R-low grade, Grade 2R-high grade, Grade X-ungradeable
Time Frame	Month 6, Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Up to 6 months: Classification A	11	13
Up to 6 months: Classification B	11	13
6 to 12 months: Classification A	10	9
6 to 12 months: Classification B	10	9

10. Secondary Outcome

Title	Incidence of Graft Loss/Re-transplantation at Month 6 and Month 12
Description	Incidence of graft loss/re-transplantation at Month 6 and Month 12
Time Frame	Month 6, Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 6	0	0
Month 12	1	1

11. Secondary Outcome

Title	Incidence of Bronchiolitis Obliterans Syndrome (BOS) at Month 6 and Month 12
Description	Incidence of Bronchiolitis obliterans syndrome (BOS) at Month 6 and Month 12 BOS 0 is FEV1 > 90% of baseline and FEF25-75% > 75% of baseline; BOS 0-p is FEV1 81-90% of baseline and/or FEF25-75% ≤ 75% of baseline; BOS 1 is FEV1 66-80% of baseline; BOS 2 is FEV1 51-65% of baseline; BOS 3 is FEV1 ≤ 50% of baseline
Time Frame	Month 6, Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 6 - Total (all grades)	66	61
Month 6 - BOS 0	36	40
Month 6 - BOS 0p	26	14
Month 6 - BOS 1	3	5
Month 6 - BOS 2	1	0
Month 6 - BOS 3	0	2
Month 6 - BOS (>/=1)	4	7
Month 12 - Total (all grades)	66	61
Month 12 - BOS 0	35	38
Month 12 - BOS 0p	26	14
Month 12 - BOS 1	3	5
Month 12 - BOS 2	1	1
Month 12 - BOS 3	1	3
Month 12 - BOS (>/=1)	5	9

12. Secondary Outcome

Title	Incidence of Death at Month 6 and Month 12
Description	Incidence of death at Month 6 and Month 12
Time Frame	Month 6, Month 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 6	0	0
Month 12	3	1

13. Secondary Outcome

Title	Quality of Life (QoL, SF36) at Month 6 and Month 12
Description	Quality of Life (QoL, SF36) at Month 6 and Month 12 Scores can range from a minimum of 0 (maximum disability) to a maximum of 100 (no disability).
Time Frame	Month 6, Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 6: Physical component summary score	46.9 (7.6)	48.9 (7.3)
Month 6: Mental component summary score	51.5 (10.8)	52.6 (8.1)
Month 6: Physical functioning	78.8 (20.9)	84.1 (16.8)
Month 6: Role-Physical	71.1 (23.2)	77.1 (24.2)
Month 6: Bodily pain	76.4 (27.9)	81.3 (23.4)
Month 6: General health perception	65.4 (19.2)	70.6 (19.9)
Month 6: Vitality	67.4 (18.0)	70.0 (14.6)
Month 6:Social functioning	84.1 (22.6)	88.9 (17.6)
Month 6: Role-Emotional	84.7 (22.4)	84.8 (17.9)
Month 6: Mental health	78.5 (17.2)	81.0 (12.8)
Month 12: Physical component summary score	47.2 (8.8)	47.7 (7.1)
Month 12: Mental component summary score	49.7 (11.8)	53.8 (9.1)
Month 12: Physical functioning	77.4 (21.8)	82.5 (20.0)
Month 12: Role-Physical	68.3 (26.8)	78.0 (22.9)
Month 12: Bodily Pain	76.8 (27.0)	80.1 (22.7)
Month 12: General health perception	66.7 (17.3)	65.8 (20.3)
Month 12: Vitality	65.7 (19.4)	69.9 (17.5)
Month 12: Social functioning	82.3 (23.0)	90.5 (16.1)
Month 12: Role-Emotional	79.4 (27.3)	86.2 (20.5)
Month 12: Mental health	75.4 (18.2)	81.8 (14.8)

14. Secondary Outcome

Title	Exercise Capacity 6-Minute Walk Test(6MWT) at Month 6 and Month 12
Description	Exercise capacity (6MWT) at Month 6 and Month 12 Measured by the Borg Scale. THE BORG SCALE 0 is Nothing at all, 0.5 is Very, very slight (just noticeable); 1 is Very slight, 2 is Slight (light); 3 is Moderate; 4 is Somewhat severe; 5 is Severe (heavy), 7 is Very severe, 10 is Very, very severe (maximal)The higher the Borg score implies increased shortness of breath and/or increased fatigue.
Time Frame	Month 6, Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 6-Borg score - Before start of test	0.47 (0.78)	0.39 (0.77)
Month 6-Borg score - At end of test	1.75 (1.58)	1.64 (1.31)
Month 12-Borg score - Before start of test	0.38 (0.94)	0.42 (0.79)
Month 12-Borg score - At end of test	2.08 (1.58)	2.06 (1.85)

15. Secondary Outcome

Title	Incidence of Treated Arterial Hypertension up to Month 12
Description	Incidence of treated of arterial hypertension up to Month 12
Time Frame	up to Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	2	1
Month 3	2	1
Month 6	2	1
Month 9	3	1
Month 12	4	1

16. Secondary Outcome

Title	Incidence of Diabetes Mellitus up to Month 12
Description	Incidence of Diabetes Mellitus up to Month 12
Time Frame	up to Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	0	0
Month 3	0	0
Month 6	0	1
Month 9	1	1
Month 12	1	1

17. Secondary Outcome

Title	Trough Levels of Everolimus at Month 1, 3, 6, 9, 12
Description	Trough levels of everolimus at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids
Measure Participants	67
Month 1	4.2 (1.4)
Month 3	4.4 (1.2)
Month 6	4.1 (1.2)
Month 9	4.5 (1.6)
Month 12	4.3 (1.1)

18. Secondary Outcome

Title	Adherence to Target Ranges of Everolimus at Month 1, 3, 6, 9, 12
Description	Adherence to target ranges of everolimus at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids
Measure Participants	67
Month 1 Below Target Range	10 (1.4)
Month 1 Within Target Range	42 (1.2)
Month 1 Above Target Range	14 (1.2)
Month 3 Below Target Range	5 (1.6)
Month 3 Within Target Range	41 (1.1)
Month 3 Above Target Range	15
Month 6 Below Target Range	7
Month 6 Within Target Range	39
Month 6 Above Target Range	12
Month 9 Below Target Range	5
Month 9 Within Target Range	34
Month 9 Above Target Range	13
Month 12 Below Target Range	3
Month 12 Within Target Range	38
Month 12 Above Target Range	9

19. Secondary Outcome

Title	Trough Levels of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12
Description	Trough levels of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	61 (21.83)	106 (21.25)
Month 3	59.65 (20.43)	109 (24.95)
Month 6	58.50 (12.84)	103 (32.95)
Month 9	57.59 (23.26)	107 (29.13)
Month 12	69.33 (48.41)	108 (27.82)

20. Secondary Outcome

Title	Adherence to Target Ranges of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12
Description	Adherence to target ranges of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1 Below Target Range	0 (21.83)	8 (21.25)
Month 1 Within Target Range	18 (20.43)	8 (24.95)
Month 1 Above Target Range	3 (12.84)	0 (32.95)
Month 3 Below Target Range	0 (23.26)	4 (29.13)
Month 3 Within Target Range	18 (48.41)	10 (27.82)
Month 3 Above Target Range	2	0
Month 6 Below Target Range	0	6
Month 6 Within Target Range	18	8
Month 6 Above Target Range	2	0
Month 9 Below Target Range	0	4
Month 9 Within Target Range	16	9
Month 9 Above Target Range	1	0
Month 12 Below Target Range	0	3
Month 12 Within Target Range	16	10
Month 12 Above Target Range	5	0

21. Secondary Outcome

Title	Trough Levels of Tacrolimus at Month 1, 3, 6, 9, 12
Description	Trough levels of Tacrolimus at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	5.07 (1.80)	10.44 (2.73)
Month 3	5.18 (2.02)	10.53 (2.88)
Month 6	4.70 (1.98)	10.09 (3.37)
Month 9	5.78 (4.18)	10.67 (3.44)
Month 12	5.19 (2.36)	9.66 (3.01)

22. Secondary Outcome

Title	Adherence to Target Ranges of Tacrolimus at Month 1, 3, 6, 9, 12
Description	Adherence to target ranges of Tacrolimus at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1 Below Target Range	3 (21.83)	0 (21.25)
Month 1 Within Target Range	24 (20.43)	45 (24.95)
Month 1 Above Target Range	17 (12.84)	0 (32.95)
Month 3 Below Target Range	3 (23.26)	0 (29.13)
Month 3 Within Target Range	23 (48.41)	47 (27.82)
Month 3 Above Target Range	18	0
Month 6 Below Target Range	5	1
Month 6 Within Target Range	23	45
Month 6 Above Target Range	12	0
Month 9 Below Target Range	2	0
Month 9 Within Target Range	18	46
Month 9 Above Target Range	18	0
Month 12 Below Target Range	3	0
Month 12 Within Target Range	23	47
Month 12 Above Target Range	15	0

23. Secondary Outcome

Title	Incidence of Bacterial, Viral, and Fungal Infections at Month 12
Description	Incidence of bacterial, viral, and fungal infections at Month 12
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Bacterial infections	3	4
Viral infections	14	20
Fungal infections	3	0

24. Secondary Outcome

Title	Triglyceride Levels at Month 1, 3, 6, 9, 12
Description	Triglyceride levels at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	2.6 (1.4)	2.0 (0.9)
Month 3	2.7 (1.3)	2.1 (1.0)
Month 6	2.6 (1.2)	2.0 (1.1)
Month 9	2.7 (1.3)	2.0 (1.0)
Month 12	2.7 (1.5)	2.1 (0.9)

25. Secondary Outcome

Title	Total Cholesterol Levels at Month 1, 3, 6, 9, 12
Description	Total Cholesterol levels at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	0.8 (0.8)	-0.2 (0.7)
Month 3	1.0 (0.8)	-0.1 (0.9)
Month 6	1.1 (0.9)	-0.2 (0.8)
Month 9	1.1 (0.9)	-0.1 (0.9)
Month 12	0.8 (1.1)	-0.1 (0.8)

26. Secondary Outcome

Title	Low-Density Lipoprotein (LDL)Cholesterol Levels at Month 1, 3, 6, 9, 12
Description	LDL Cholesterol levels at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	0.4 (0.8)	0.0 (0.5)
Month 3	0.6 (0.7)	-0.0 (0.6)
Month 6	0.7 (0.8)	-0.0 (0.6)
Month 9	0.8 (0.8)	0.1 (0.7)
Month 12	0.5 (0.9)	0.1 (0.6)

27. Secondary Outcome

Title	High-Density Lipoprotein (HDL)Cholesterol Levels at Month 1, 3, 6, 9, 12
Description	HDL Cholesterol levels at Month 1, 3, 6, 9, 12
Time Frame	Month 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Arm/Group Title	Quadruple Low Level IS Regimen	Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids	centre specific CNI-based triple drug immunosuppression (IS)
Measure Participants	67	63
Month 1	0.1 (0.3)	-0.1 (0.3)
Month 3	0.1 (0.3)	-0.0 (0.4)
Month 6	0.1 (0.4)	-0.0 (0.4)
Month 9	0.0 (0.4)	-0.0 (0.4)
Month 12	0.0 (0.5)	-0.0 (0.4)

Adverse Events

Time Frame	Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until 12 months.
Arm/Group Title	Quadruple Low Level IS Regimen		Centre Specific Triple IS Regimen
Arm/Group Description	quadruple immunosuppressive (IS) regimen consisting of everolimus, CNI, MPA and steroids		centre specific CNI-based triple drug immunosuppression (IS)
All Cause Mortality
	Quadruple Low Level IS Regimen		Centre Specific Triple IS Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Quadruple Low Level IS Regimen		Centre Specific Triple IS Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/67 (43.3%)		22/63 (34.9%)
Blood and lymphatic system disorders
LEUKOPENIA	0/67 (0%)		1/63 (1.6%)
Cardiac disorders
ACUTE CORONARY SYNDROME	0/67 (0%)		1/63 (1.6%)
ACUTE MYOCARDIAL INFARCTION	0/67 (0%)		1/63 (1.6%)
ATRIAL FLUTTER	1/67 (1.5%)		0/63 (0%)
CARDIAC FAILURE CONGESTIVE	1/67 (1.5%)		0/63 (0%)
COR PULMONALE	1/67 (1.5%)		0/63 (0%)
CORONARY ARTERY DISEASE	0/67 (0%)		1/63 (1.6%)
RIGHT VENTRICULAR FAILURE	2/67 (3%)		0/63 (0%)
SINUS TACHYCARDIA	0/67 (0%)		1/63 (1.6%)
Congenital, familial and genetic disorders
HYDROCELE	1/67 (1.5%)		0/63 (0%)
Eye disorders
RETINAL DETACHMENT	1/67 (1.5%)		0/63 (0%)
RETINAL VEIN OCCLUSION	0/67 (0%)		1/63 (1.6%)
Gastrointestinal disorders
ABDOMINAL PAIN UPPER	1/67 (1.5%)		0/63 (0%)
DIARRHOEA	1/67 (1.5%)		2/63 (3.2%)
DUODENAL ULCER HAEMORRHAGE	0/67 (0%)		1/63 (1.6%)
GASTRIC ULCER	1/67 (1.5%)		0/63 (0%)
GASTROINTESTINAL HAEMORRHAGE	0/67 (0%)		1/63 (1.6%)
GASTROOESOPHAGEAL REFLUX DISEASE	1/67 (1.5%)		0/63 (0%)
HAEMORRHAGIC EROSIVE GASTRITIS	1/67 (1.5%)		0/63 (0%)
INGUINAL HERNIA	0/67 (0%)		1/63 (1.6%)
General disorders
CHEST PAIN	3/67 (4.5%)		0/63 (0%)
CHILLS	1/67 (1.5%)		0/63 (0%)
HERNIA	0/67 (0%)		2/63 (3.2%)
INFLAMMATION	0/67 (0%)		1/63 (1.6%)
LOCAL SWELLING	0/67 (0%)		1/63 (1.6%)
LOCALISED OEDEMA	1/67 (1.5%)		0/63 (0%)
OEDEMA PERIPHERAL	3/67 (4.5%)		0/63 (0%)
PERIPHERAL SWELLING	1/67 (1.5%)		0/63 (0%)
PYREXIA	4/67 (6%)		3/63 (4.8%)
Immune system disorders
LUNG TRANSPLANT REJECTION	5/67 (7.5%)		0/63 (0%)
Infections and infestations
ATYPICAL PNEUMONIA	0/67 (0%)		1/63 (1.6%)
BRONCHITIS	2/67 (3%)		1/63 (1.6%)
BRONCHITIS BACTERIAL	1/67 (1.5%)		0/63 (0%)
BRONCHITIS VIRAL	0/67 (0%)		1/63 (1.6%)
CYTOMEGALOVIRUS INFECTION	1/67 (1.5%)		4/63 (6.3%)
GASTROENTERITIS	1/67 (1.5%)		0/63 (0%)
GASTROINTESTINAL INFECTION	0/67 (0%)		1/63 (1.6%)
INFECTION	3/67 (4.5%)		2/63 (3.2%)
LUNG INFECTION	0/67 (0%)		1/63 (1.6%)
PNEUMONIA	3/67 (4.5%)		3/63 (4.8%)
PNEUMONIA VIRAL	0/67 (0%)		1/63 (1.6%)
PYELONEPHRITIS	1/67 (1.5%)		0/63 (0%)
RESPIRATORY SYNCYTIAL VIRUS INFECTION	0/67 (0%)		1/63 (1.6%)
RESPIRATORY TRACT INFECTION	1/67 (1.5%)		3/63 (4.8%)
SUPERINFECTION BACTERIAL	0/67 (0%)		1/63 (1.6%)
TRACHEOBRONCHITIS	1/67 (1.5%)		0/63 (0%)
URINARY TRACT INFECTION	0/67 (0%)		1/63 (1.6%)
UROSEPSIS	1/67 (1.5%)		0/63 (0%)
Injury, poisoning and procedural complications
COMPLICATIONS OF TRANSPLANTED LUNG	1/67 (1.5%)		0/63 (0%)
MATERNAL EXPOSURE DURING PREGNANCY	0/67 (0%)		1/63 (1.6%)
PELVIC FRACTURE	1/67 (1.5%)		0/63 (0%)
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED	1/67 (1.5%)		0/63 (0%)
C-REACTIVE PROTEIN INCREASED	1/67 (1.5%)		0/63 (0%)
FORCED EXPIRATORY VOLUME DECREASED	9/67 (13.4%)		5/63 (7.9%)
IMMUNOSUPPRESSANT DRUG LEVEL INCREASED	0/67 (0%)		1/63 (1.6%)
PULMONARY FUNCTION TEST DECREASED	1/67 (1.5%)		0/63 (0%)
WEIGHT DECREASED	1/67 (1.5%)		0/63 (0%)
Metabolism and nutrition disorders
DEHYDRATION	1/67 (1.5%)		0/63 (0%)
HYPERKALAEMIA	0/67 (0%)		1/63 (1.6%)
Musculoskeletal and connective tissue disorders
PSEUDARTHROSIS	1/67 (1.5%)		0/63 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLADDER TRANSITIONAL CELL CARCINOMA	1/67 (1.5%)		0/63 (0%)
SQUAMOUS CELL CARCINOMA	1/67 (1.5%)		0/63 (0%)
Nervous system disorders
HEADACHE	1/67 (1.5%)		0/63 (0%)
PARAPARESIS	1/67 (1.5%)		0/63 (0%)
SCIATICA	1/67 (1.5%)		0/63 (0%)
TREMOR	1/67 (1.5%)		0/63 (0%)
Pregnancy, puerperium and perinatal conditions
ABORTION SPONTANEOUS	0/67 (0%)		1/63 (1.6%)
Renal and urinary disorders
ACUTE KIDNEY INJURY	1/67 (1.5%)		1/63 (1.6%)
URGE INCONTINENCE	1/67 (1.5%)		0/63 (0%)
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA	2/67 (3%)		0/63 (0%)
Respiratory, thoracic and mediastinal disorders
BRONCHOSTENOSIS	1/67 (1.5%)		2/63 (3.2%)
DYSPNOEA	3/67 (4.5%)		4/63 (6.3%)
DYSPNOEA EXERTIONAL	1/67 (1.5%)		0/63 (0%)
EPISTAXIS	1/67 (1.5%)		0/63 (0%)
HAEMOPTYSIS	0/67 (0%)		1/63 (1.6%)
IDIOPATHIC PULMONARY FIBROSIS	0/67 (0%)		1/63 (1.6%)
LUNG DISORDER	1/67 (1.5%)		0/63 (0%)
LUNG INFILTRATION	3/67 (4.5%)		0/63 (0%)
OBLITERATIVE BRONCHIOLITIS	3/67 (4.5%)		1/63 (1.6%)
ORGANISING PNEUMONIA	1/67 (1.5%)		0/63 (0%)
PAINFUL RESPIRATION	2/67 (3%)		0/63 (0%)
PLEURAL EFFUSION	0/67 (0%)		2/63 (3.2%)
PULMONARY EMBOLISM	1/67 (1.5%)		2/63 (3.2%)
SLEEP APNOEA SYNDROME	1/67 (1.5%)		1/63 (1.6%)
Skin and subcutaneous tissue disorders
NIGHT SWEATS	1/67 (1.5%)		0/63 (0%)
Vascular disorders
DEEP VEIN THROMBOSIS	1/67 (1.5%)		0/63 (0%)
LYMPHOCELE	0/67 (0%)		1/63 (1.6%)
LYMPHORRHOEA	0/67 (0%)		1/63 (1.6%)
PERIPHERAL VENOUS DISEASE	1/67 (1.5%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Quadruple Low Level IS Regimen		Centre Specific Triple IS Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/67 (92.5%)		58/63 (92.1%)
Blood and lymphatic system disorders
ANAEMIA	6/67 (9%)		3/63 (4.8%)
LEUKOPENIA	15/67 (22.4%)		19/63 (30.2%)
Gastrointestinal disorders
DIARRHOEA	9/67 (13.4%)		10/63 (15.9%)
NAUSEA	9/67 (13.4%)		10/63 (15.9%)
VOMITING	5/67 (7.5%)		4/63 (6.3%)
General disorders
CHEST PAIN	2/67 (3%)		5/63 (7.9%)
OEDEMA PERIPHERAL	19/67 (28.4%)		10/63 (15.9%)
PYREXIA	1/67 (1.5%)		5/63 (7.9%)
Infections and infestations
CYTOMEGALOVIRUS INFECTION	10/67 (14.9%)		11/63 (17.5%)
LOWER RESPIRATORY TRACT INFECTION	2/67 (3%)		4/63 (6.3%)
NASOPHARYNGITIS	17/67 (25.4%)		17/63 (27%)
RESPIRATORY TRACT INFECTION	8/67 (11.9%)		7/63 (11.1%)
URINARY TRACT INFECTION	4/67 (6%)		2/63 (3.2%)
Injury, poisoning and procedural complications
COMPLICATIONS OF TRANSPLANTED LUNG	0/67 (0%)		4/63 (6.3%)
Investigations
BRONCHOALVEOLAR LAVAGE ABNORMAL	3/67 (4.5%)		6/63 (9.5%)
C-REACTIVE PROTEIN INCREASED	2/67 (3%)		4/63 (6.3%)
FORCED EXPIRATORY VOLUME DECREASED	7/67 (10.4%)		8/63 (12.7%)
PULMONARY FUNCTION TEST DECREASED	6/67 (9%)		3/63 (4.8%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	2/67 (3%)		5/63 (7.9%)
BACK PAIN	2/67 (3%)		5/63 (7.9%)
PAIN IN EXTREMITY	8/67 (11.9%)		5/63 (7.9%)
Nervous system disorders
HEADACHE	8/67 (11.9%)		9/63 (14.3%)
MIGRAINE	3/67 (4.5%)		4/63 (6.3%)
Respiratory, thoracic and mediastinal disorders
COUGH	10/67 (14.9%)		7/63 (11.1%)
OROPHARYNGEAL PAIN	4/67 (6%)		4/63 (6.3%)
PRODUCTIVE COUGH	1/67 (1.5%)		5/63 (7.9%)
Skin and subcutaneous tissue disorders
ACNE	12/67 (17.9%)		1/63 (1.6%)
Vascular disorders
HYPERTENSION	7/67 (10.4%)		4/63 (6.3%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single- site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.