Trial Outcomes & Findings for Mycophenolic Acid (MPA) Monotherapy in Liver Transplantation (NCT NCT01230502)
NCT ID: NCT01230502
Last Updated: 2014-05-07
Results Overview
This outcome measure is used to determine if the reduction of calcineurin inhibitor immunosuppression leads to improved native kidney function. Native kidney function is assessed using the Modification of Diet in Renal Disease (MDRD) estimation of glomerular filtration rate (GFR) from serum or plasma creatinine samples at the reported time points. Reference intervals include: Healthy 18 years and up: 60-120 mL/min/1.73 sqm Chronic kidney disease: GFR \< 60 mL/min/1.73 sqm Kidney failure: GFR \< 15 mL/min/1.73 sqm
Recruitment status
TERMINATED
Study phase
NA
Target enrollment
11 participants
Primary outcome timeframe
6 months post enrollment/randomization
Results posted on
2014-05-07
Participant Flow
11 participants consented and were enrolled in the study. However, 2 of the subjects screen failed and did not participate in the study beyond providing their consent to participate. Thus only 9 subjects consented to and "started" the study and these 9 subjects are analyzed in the results.
Participant milestones
| Measure |
Group 3: Donor Specific Regulation (DSR) -, Standard of Care
Subjects who test Donor specific regulation (DSR) negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression.
data and sample collection: Group 3 : DSR (-) standard of care:
These subjects are those who were DSR negative and/or DSA positive at enrollment and therefore are not eligible for the withdrawal aspect of the study. These subjects will be maintained on standard of care immunosuppression consisting of tacrolimus and mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment. These subjects will be asked to provide heath information and donate blood, exclusively for research testing, at the same 6 month intervals as those in the other two arms of the study, and will be followed for 24 months.
|
Group 2 Donor Specific Regulation (DSR) +; Standard of Care
Subjects that are DSR (donor specific regulation) positive and randomized (1:1)to Group 2 will remain on standard of care immunosuppression.
data and sample collection: Group 2 : DSR (+)standard of care:
These subjects will be maintained on standard of care immunosuppression consisting of Tacrolimus and Mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment.
Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples
|
Group 1 Donor Specific Regulation (DSR) +, MPA Monotherapy
Subjects that are Donor specific regulation (DSR) positive and randomized (1:1) to Group 1 will begin a taper off tacrolimus for 6 months, after repeat DSR testing at 6 months subject will either discontinue tacrolimus if they remain DSR negative or remain at reduced dose if converted to DSR positive
Withdrawal of Tacrolimus to mycophenolate monotherapy: Group 1:
Mycophenolate sodium : Myfortic therapy will be maintained at a target dose of 720mg BID.
Tacrolimus doses will be lowered to achieve levels of 3-5 ng/ml. 6 months later, immunological monitoring will be repeated and tacrolimus will be completely discontinued if the subject remains DSR + without development of donor specific antibodies (DSA). Those who become DSR- or develop DSA will remain on a tacrolimus dose achieving levels of 3-5 ng/ml, and will not undergone any additional reduction.
Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples.
|
|---|---|---|---|
|
Overall Study
STARTED
|
9
|
0
|
0
|
|
Overall Study
COMPLETED
|
9
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Mycophenolic Acid (MPA) Monotherapy in Liver Transplantation
Baseline characteristics by cohort
| Measure |
Group 3: Donor Specific Regulation DSR -, Standard of Care
n=9 Participants
Subjects who test DSR (donor specific regulation) negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression.
data and sample collection: Group 3 : DSR(-) standard of care:
These subjects are those who were DSR negative and/or DSA positive at enrollment and therefore are not eligible for the withdrawal aspect of the study. These subjects will be maintained on standard of care immunosuppression consisting of tacrolimus and mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment. These subjects will be asked to provide heath information and donate blood, exclusively for research testing, at the same 6 month intervals as those in the other two arms of the study, and will be followed for 24 months.
|
Group 2 Donor Specific Regulation DSR +; Standard of Care
Subjects that are DSR (donor specific regulation) positive and randomized (1:1)to Group 2 will remain on standard of care immunosuppression.
data and sample collection: Group 2 : DSR(+) standard of care:
These subjects will be maintained on standard of care immunosuppression consisting of tacrolimus and mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment.
Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples
|
Group 1 Donor Specific Regulation (DSR) +, MPA Monotherapy
Subjects that are DSR (donor specific regulation) positive and randomized (1:1)to Group 1 will begin a taper off tacrolimus for 6 months, after repeat DSR testing at 6 months subject will either discontinue tacrolimus if they remain DSR negative or remain at reduced dose if converted to DSR positive
Withdrawal of Tacrolimus to mycophenolate monotherapy: Group 1:
Mycophenolate sodium : Myfortic therapy will be maintained at a target dose of 720mg BID.
Tacrolimus doses will be lowered to achieve levels of 3-5 ng/ml. 6 months later, immunological monitoring will be repeated and tacrolimus will be completely discontinued if the subject remains DSR + without development of donor specific antibodies (DSA). Those who become DSR- or develop DSA will remain on a tacrolimus dose achieving levels of 3-5 ng/ml, and will not undergone any additional reduction.
Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples.
|
Total
n=9 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
51 years
STANDARD_DEVIATION 14.757 • n=5 Participants
|
—
|
—
|
51 years
STANDARD_DEVIATION 14.76 • n=4 Participants
|
|
Age, Categorical
<=18 years
|
0 participants
n=5 Participants
|
—
|
—
|
0 participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 participants
n=5 Participants
|
—
|
—
|
8 participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
1 participants
n=5 Participants
|
—
|
—
|
1 participants
n=4 Participants
|
|
Gender
Female
|
3 participants
n=5 Participants
|
—
|
—
|
3 participants
n=4 Participants
|
|
Gender
Male
|
6 participants
n=5 Participants
|
—
|
—
|
6 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=5 Participants
|
—
|
—
|
9 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 6 months post enrollment/randomizationThis outcome measure is used to determine if the reduction of calcineurin inhibitor immunosuppression leads to improved native kidney function. Native kidney function is assessed using the Modification of Diet in Renal Disease (MDRD) estimation of glomerular filtration rate (GFR) from serum or plasma creatinine samples at the reported time points. Reference intervals include: Healthy 18 years and up: 60-120 mL/min/1.73 sqm Chronic kidney disease: GFR \< 60 mL/min/1.73 sqm Kidney failure: GFR \< 15 mL/min/1.73 sqm
Outcome measures
| Measure |
Group 3: DSR (-), Standard of Care
n=7 Participants
Subjects who test DSR negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression.
data and sample collection: Group 3 : DSR (-) standard of care:
These subjects are those who were DSR negative and/or DSA positive at enrollment and therefore are not eligible for the withdrawal aspect of the study. These subjects will be maintained on standard of care immunosuppression consisting of tacrolimus and mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment. These subjects will be asked to provide heath information and donate blood, exclusively for research testing, at the same 6 month intervals as those in the other two arms of the study, and will be followed for 24 months.
|
Group 2 DSR (+); Standard of Care
Subjects that are DSR positive and randomized (1:1)to Group 2 will remain on standard of care immunosuppression.
data and sample collection: Group 2 : DSR (+)standard of care:
These subjects will be maintained on standard of care immunosuppression consisting of tacrolimus and mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment.
Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples
|
Group 1 DSR (+), Withdrawal of Tacrolimus to MPA Monotherapy
Subjects that are DSR positive and randomized (1:1)to Group 1 will begin a taper off tacrolimus for 6 months, after repeat DSR testing at 6 months subject will either discontinue tacrolimus if they remain DSR negative or remain at reduced dose if converted to DSR positive
Withdrawal of Tacrolimus to mycophenolate monotherapy: Group 1:
Mycophenolate sodium : Myfortic therapy will be maintained at a target dose of 720mg BID.
Tacrolimus doses will be lowered to achieve levels of 3-5 ng/ml. 6 months later, immunological monitoring will be repeated and tacrolimus will be completely discontinued if the subject remains DSR + without development of donor specific antibodies (DSA). Those who become DSR- or develop DSA will remain on a tacrolimus dose achieving levels of 3-5 ng/ml, and will not undergone any additional reduction.
Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples.
|
|---|---|---|---|
|
Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR)
|
60.14 mL/min/1.73 sqm
Standard Deviation 16.39
|
—
|
—
|
PRIMARY outcome
Timeframe: 12 months post enrollment/randomizationThis outcome measure is used to determine if the reduction of calcineurin inhibitor immunosuppression leads to improved native kidney function. Native kidney function is assessed using the Modification of Diet in Renal Disease (MDRD) estimation of glomerular filtration rate (GFR) from serum or plasma creatinine samples at the reported time points. Reference intervals include: Healthy 18 years and up: 60-120 mL/min/1.73 sqm Chronic kidney disease: GFR \< 60 mL/min/1.73 sqm Kidney failure: GFR \< 15 mL/min/1.73 sqm
Outcome measures
| Measure |
Group 3: DSR (-), Standard of Care
n=5 Participants
Subjects who test DSR negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression.
data and sample collection: Group 3 : DSR (-) standard of care:
These subjects are those who were DSR negative and/or DSA positive at enrollment and therefore are not eligible for the withdrawal aspect of the study. These subjects will be maintained on standard of care immunosuppression consisting of tacrolimus and mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment. These subjects will be asked to provide heath information and donate blood, exclusively for research testing, at the same 6 month intervals as those in the other two arms of the study, and will be followed for 24 months.
|
Group 2 DSR (+); Standard of Care
Subjects that are DSR positive and randomized (1:1)to Group 2 will remain on standard of care immunosuppression.
data and sample collection: Group 2 : DSR (+)standard of care:
These subjects will be maintained on standard of care immunosuppression consisting of tacrolimus and mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment.
Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples
|
Group 1 DSR (+), Withdrawal of Tacrolimus to MPA Monotherapy
Subjects that are DSR positive and randomized (1:1)to Group 1 will begin a taper off tacrolimus for 6 months, after repeat DSR testing at 6 months subject will either discontinue tacrolimus if they remain DSR negative or remain at reduced dose if converted to DSR positive
Withdrawal of Tacrolimus to mycophenolate monotherapy: Group 1:
Mycophenolate sodium : Myfortic therapy will be maintained at a target dose of 720mg BID.
Tacrolimus doses will be lowered to achieve levels of 3-5 ng/ml. 6 months later, immunological monitoring will be repeated and tacrolimus will be completely discontinued if the subject remains DSR + without development of donor specific antibodies (DSA). Those who become DSR- or develop DSA will remain on a tacrolimus dose achieving levels of 3-5 ng/ml, and will not undergone any additional reduction.
Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples.
|
|---|---|---|---|
|
Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR)
|
82.4 mL/min/1.73 sqm
Standard Deviation 28.34
|
—
|
—
|
Adverse Events
Group 3: DSR (Donor Specific Regulation) (-), Standard of Care
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Group 2 DSR (Donor Specific Regulation) (+); Standard of Care
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Group 1 DSR (Donor Specific Regulation) (+),MPA Monotherapy
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Professor William Burlingham, PhD
University of Wisconsin
Phone: (608) 263-0119
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The PI, or his designee, must notify the sponsor at least (10) days, if possible, or as soon as possible, prior to submitting this information.
- Publication restrictions are in place
Restriction type: OTHER