ORANGE: An Observational Study on Renal Function in Kidney Transplant Participants on Immunosuppressive Therapy Containing Mycophenolate Mofetil

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01672957
• Collaborator: (none)
• Enrollment: 128
• Locations: 2
• Duration (Months): 46
• Patients Per Site: 64
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

This observational study will evaluate renal function in participants who underwent renal allograft transplantation and are started on combined immunosuppressive treatment containing mycophenolate mofetil (CellCept). Eligible participants will be followed for 12 months following transplantation.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation	Drug: Mycophenolate Mofetil; Drug: Immunosuppressive Therapy

Detailed Description

The participant sampling method used in the Orange study was consecutive sampling, a non-probability sampling method where each participant meeting the study's inclusion and exclusion criteria is selected and enrolled in the study until the pre-set sample size is achieved.

Thus, in the Orange study de novo kidney transplanted participants, who were on mycophenolate mofetil immunosuppressive combination therapy in routine clinical practice, were selected in a consecutive manner (a non-probability sampling method) if they met the inclusion/exclusion criteria until 128 participants were recruited to the study.

Study Design

• Study Type: Observational
• Actual Enrollment: 128 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Non-interventional Clinical Study With Target of Kidney Function Follow-up in Routine Clinical Practice on De Novo Kidney Transplant Recipients Who Are on CellCept Immunosuppressive Combination Therapy in Routine Clinical Practice
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Renal Transplant Participants Renal transplant participants who will be subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, will be followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurs first. The choice of treatment will be made prior to enrolment by the treating physician. The treatment will be administered according to applicable therapeutic protocol and Summary of Product Characteristics (SmPC).

Drug: Mycophenolate Mofetil; Protocol does not specify any regimen for treatment. The choice of treatment will be made prior to enrollment by the treating physician.; Other Names: CellCept ; Drug: Immunosuppressive Therapy; Protocol does not specify any particular immunosuppressive drug and regimen for treatment. The choice of immunosuppressive therapy will be made prior to enrollment by the treating physician.

Outcome Measures

Primary Outcome Measures

1. Creatinine Clearance at 1 Month After Transplantation [Month 1]

   Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.

2. Creatinine Clearance at Month 6 After Transplantation [Month 6]

   Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 mL/min and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.

3. Creatinine Clearance at Month 12 After Transplantation [Month 12]

   Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 mL/min and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.

4. Glomerular Filtration Rate (GFR) at Month 1 After Transplantation [Month 1]

   GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is greater than (>) 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR less than (<) 15 mL/min indicates kidney failure.

5. GFR at Month 6 After Transplantation [Month 6]

   GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR < 15 mL/min indicates kidney failure.

6. GFR at Month 12 After Transplantation [Month 12]

   GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR < 15 mL/min indicates kidney failure.

Secondary Outcome Measures

1. Mean Dose of Mycophenolate Mofetil [Baseline, Months 1, 6, and 12]

2. Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil [Baseline, Months 1, 6, and 12]

   Participants could have received more than one other immunosuppressive agents, at the discretion of treating physician. Percentage of participants who received 1 other immunosuppressive agent, 2 other immunosuppressive agents, and 3 other immunosuppressive agents are reported.

3. Percentage of Participants With Acute Rejection [Baseline to Month 1, Months 2 to 6, Months 7 to 12]

   Percentage of participants who experienced acute rejection within 1 month of transplantation, Month 2 to Month 6 after transplantation, Month 7 to Month 12 after transplantation are reported.

4. Percentage of Participants With Graft Survival [Months 1, 6, and 12]

   Graft survival was defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), re-transplant or death during the first 12 months after transplantation.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participants who underwent renal allograft transplantation and are started on combined immunosuppressive treatment containing mycophenolate mofetil in accordance with the indication provided by the SmPC of mycophenolate mofetil

• Date of study enrollment is the date of kidney transplantation

Exclusion Criteria:

• Contraindication included in the SmPC for capecitabine (Xeloda) prevailed, like: Hypersensitivity to active ingredient or any of the excipients of the product; Pregnancy and lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Budapest		Hungary	1082
2		Pecs		Hungary	7624

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01672957
• Other Study ID Numbers: ML27844
• First Posted: Aug 27, 2012
• Last Update Posted: Oct 11, 2016
• Last Verified: Aug 1, 2016

• Additional relevant MeSH terms: Mycophenolic Acid; Immunosuppressive Agents

Study Results

Participant Flow

Pre-assignment Detail	If Informed Consent Form (ICF) was signed after the transplantation, it was considered as a major protocol violation and reported separately from protocol violation in Participant Flow.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil (CellCept), were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and Summary of Product Characteristics (SmPC). The study protocol did not specify any treatment regimen.
Period Title: Overall Study
STARTED	128
Intent-to-treat (ITT) Population	123
COMPLETED	73
NOT COMPLETED	55

Baseline Characteristics

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Overall Participants	123
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.60 (13.24)
Sex: Female, Male (Count of Participants)
Female	44 35.8%
Male	79 64.2%

Outcome Measures

1. Primary Outcome

Title	Creatinine Clearance at 1 Month After Transplantation
Description	Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.
Time Frame	Month 1

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for creatinine clearance at specified time-point.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Measure Participants	107
Mean (Standard Deviation) [mL/min]	65.82 (18.32)

2. Primary Outcome

Title	Creatinine Clearance at Month 6 After Transplantation
Description	Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 mL/min and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for creatinine clearance at specified time-point.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Measure Participants	76
Mean (Standard Deviation) [mL/min]	73.38 (19.43)

3. Primary Outcome

Title	Creatinine Clearance at Month 12 After Transplantation
Description	Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 mL/min and for females, 90-125 mL/min. Creatinine clearance decreases with age. A low creatinine clearance rate indicates poor kidney function.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for creatinine clearance at specified time-point.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Measure Participants	70
Mean (Standard Deviation) [mL/min]	69.69 (21.05)

4. Primary Outcome

Title	Glomerular Filtration Rate (GFR) at Month 1 After Transplantation
Description	GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is greater than (>) 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR less than (<) 15 mL/min indicates kidney failure.
Time Frame	Month 1

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for GFR at specified time-point.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Measure Participants	118
Mean (Standard Deviation) [mL/min]	53.54 (33.43)

5. Primary Outcome

Title	GFR at Month 6 After Transplantation
Description	GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR < 15 mL/min indicates kidney failure.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for GFR at specified time-point.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Measure Participants	83
Mean (Standard Deviation) [mL/min]	56.78 (15.36)

6. Primary Outcome

Title	GFR at Month 12 After Transplantation
Description	GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicates poor kidney function. A GFR < 15 mL/min indicates kidney failure.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for GFR at specified time-point.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Measure Participants	65
Mean (Standard Deviation) [mL/min]	58.03 (16.29)

7. Secondary Outcome

Title	Mean Dose of Mycophenolate Mofetil
Time Frame	Baseline, Months 1, 6, and 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for this outcome measure. Here 'n' signifies number of participants evaluable at specified time-points.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Measure Participants	121
Baseline (n=121)	2033.06 (357.86)
Month 1 (n=119)	1718.49 (543.21)
Month 6 (n=88)	1457.39 (754.51)
Month 12 (n=69)	1539.86 (669.21)

8. Secondary Outcome

Title	Percentage of Participants Who Received Other Immunosuppressive Agents in Combination With Mycophenolate Mofetil
Description	Participants could have received more than one other immunosuppressive agents, at the discretion of treating physician. Percentage of participants who received 1 other immunosuppressive agent, 2 other immunosuppressive agents, and 3 other immunosuppressive agents are reported.
Time Frame	Baseline, Months 1, 6, and 12

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed = participants evaluable for this outcome measure. Here 'n' signifies number of participants evaluable at specified time-points.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Measure Participants	121
1 Other agent: at baseline (n=121)	0.8 0.7%
1 Other agent: at Month 1 (n=119)	0.8 0.7%
1 Other agent: at Month 6 (n=86)	2.3 1.9%
1 Other agent: at Month 12 (n=69)	7.2 5.9%
2 Other agents: at baseline (n=121)	90.9 73.9%
2 Other agents: at Month 1 (n=119)	99.2 80.7%
2 Other agents: at Month 6 (n=86)	97.7 79.4%
2 Other agents: at Month 12 (n=69)	92.8 75.4%
3 Other agents: at baseline (n=121)	8.3 6.7%
3 Other agents: at Month 1 (n=119)	0 0%
3 Other agents: at Month 6 (n=86)	0 0%
3 Other agents: at Month 12 (n=69)	0 0%

9. Secondary Outcome

Title	Percentage of Participants With Acute Rejection
Description	Percentage of participants who experienced acute rejection within 1 month of transplantation, Month 2 to Month 6 after transplantation, Month 7 to Month 12 after transplantation are reported.
Time Frame	Baseline to Month 1, Months 2 to 6, Months 7 to 12

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled renal transplant participants who received mycophenolate mofetil containing immunosuppressive combination therapy (safety population=128). Number of participants analyzed = participants evaluable for this outcome measure. Here 'n' signifies number of participants evaluable at specified time-points.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Measure Participants	127
Baseline to Month 1 (n=127)	16.5 13.4%
Months 2 to 6 (n=124)	0.8 0.7%
Months 7 to 12 (n=111)	0.9 0.7%

10. Secondary Outcome

Title	Percentage of Participants With Graft Survival
Description	Graft survival was defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), re-transplant or death during the first 12 months after transplantation.
Time Frame	Months 1, 6, and 12

Outcome Measure Data

Analysis Population Description

Safety population. Number of participants analyzed = participants evaluable for this outcome measure. Here 'n' signifies number of participants evaluable at specified time-points.

Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
Measure Participants	127
Month 1 (n=127)	100 81.3%
Month 6 (n=123)	99.2 80.7%
Month 12 (n=111)	98.4 80%

Adverse Events

Time Frame	From Baseline up to Month 12
Adverse Event Reporting Description	Safety population.
Arm/Group Title	Renal Transplant Participants
Arm/Group Description	Renal transplant participants who were subjected to a combined immunosuppressive treatment containing mycophenolate mofetil, were followed-up until the end of the study (after 12 months), or until the participant's death, withdrawal, or lost contact with the participant, whichever occurred first. The choice of treatment was made prior to enrollment by the treating physician. The treatment was administered according to applicable therapeutic protocol and SmPC. The study protocol did not specify any treatment regimen.
All Cause Mortality
	Renal Transplant Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Renal Transplant Participants
	Affected / at Risk (%)	# Events
Total	33/128 (25.8%)
Cardiac disorders
Acute myocardial infarction	1/128 (0.8%)
Gastrointestinal disorders
Diarrhoea	1/128 (0.8%)
General disorders
Sudden death	1/128 (0.8%)
Immune system disorders
Kidney transplant rejection	4/128 (3.1%)
Transplant rejection	14/128 (10.9%)
Infections and infestations
Cystitis	1/128 (0.8%)
Influenza	1/128 (0.8%)
Pneumonia	3/128 (2.3%)
Postoperative abscess	1/128 (0.8%)
Urinary tract infection	1/128 (0.8%)
Injury, poisoning and procedural complications
Complications of transplanted kidney	1/128 (0.8%)
Perirenal haematoma	1/128 (0.8%)
Post procedural haemorrhage	2/128 (1.6%)
Ureteric anastomosis complication	2/128 (1.6%)
Investigations
Blood creatinine increased	1/128 (0.8%)
Nervous system disorders
Cerebrovascular accident	1/128 (0.8%)
Renal and urinary disorders
Pyelocaliectasis	2/128 (1.6%)
Tubulointerstitial nephritis	1/128 (0.8%)
Ureteral disorder	1/128 (0.8%)
Ureterolithiasis	1/128 (0.8%)
Reproductive system and breast disorders
Varicocele	1/128 (0.8%)
Respiratory, thoracic and mediastinal disorders
Respiration abnormal	1/128 (0.8%)
Vascular disorders
Haematoma	2/128 (1.6%)
Other (Not Including Serious) Adverse Events
	Renal Transplant Participants
	Affected / at Risk (%)	# Events
Total	51/128 (39.8%)
Blood and lymphatic system disorders
Anemia	13/128 (10.2%)
Gastrointestinal disorders
Diarrhoea	19/128 (14.8%)
Renal and urinary disorders
Hyperuricaemia	7/128 (5.5%)
Urinary tract infection	24/128 (18.8%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection	10/128 (7.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.