Ignite Creation Date:
2024-05-05 @ 11:58 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00195988
Status:
COMPLETED
Last Update Posted:
2005-11-17
First Post:
2005-09-12
Brief Title:
Comparison of Immunosuppression Protocols After LTx in Children
Sponsor:
Childrens Memorial Health Institute Poland
Organization:
Childrens Memorial Health Institute Poland
Study Overview
Official Title:
Comparison Of Efficacy Of Two Immunosuppressive Protocols Including Tacrolimus With Or Without Mycophenolate Mofetil In Pediatric Liver Transplantation Aimed In Early Termination Of Steroid Therapy
Status:
COMPLETED
Status Verified Date:
2005-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Open label randomised prospective onecentre Investigator Driven Study
Comparison of two protocols of immunosuppression after liver Tx in children
A Study group - FK506-MMF Immunosupression protocol Methylprednisolone 10 mgkg intraoperatively iv FK506 Day 0 or 1 orally 015 mgkgD in two dosesMMF max dosage 30 mgkgD po day 0 through day 90
B Control group - Tacrolimus steroids Immunosupression protocol Methylprednisolone 10 mgkg bm intraoperatively Children 25kg bm Methylprednisolone taper from 100 mgD on day 0 to MP 10 mg on day 7 Children 25kg bm Methylprednisolone taper from 200 mgD on day 0 to MP 20 mg on day 7 Week 2-4 Prednisone - 05-03 mgkgD Week 4-12 Prednisone -03-02 mgkgD Month 4-6 Prednisone 02 - 01 mgkgD Month 7 - Steroid withdrawal FK506 Day 0 or 1 orally 015 mgkgD in two doses
Primary end points
Number of rejections number of steroid-resistant rejections
Secondary end points
Patients and graft survival Dyslipidemia one year after transplantation Hypertension one year after transplantation HyperglycemiaDiabetes de novo one year after transplantation Renal function before Tx and 1 year after Tx
Comparison of two protocols of immunosuppression after liver Tx in children
A Study group - FK506-MMF Immunosupression protocol Methylprednisolone 10 mgkg intraoperatively iv FK506 Day 0 or 1 orally 015 mgkgD in two dosesMMF max dosage 30 mgkgD po day 0 through day 90
B Control group - Tacrolimus steroids Immunosupression protocol Methylprednisolone 10 mgkg bm intraoperatively Children 25kg bm Methylprednisolone taper from 100 mgD on day 0 to MP 10 mg on day 7 Children 25kg bm Methylprednisolone taper from 200 mgD on day 0 to MP 20 mg on day 7 Week 2-4 Prednisone - 05-03 mgkgD Week 4-12 Prednisone -03-02 mgkgD Month 4-6 Prednisone 02 - 01 mgkgD Month 7 - Steroid withdrawal FK506 Day 0 or 1 orally 015 mgkgD in two doses
Primary end points
Number of rejections number of steroid-resistant rejections
Secondary end points
Patients and graft survival Dyslipidemia one year after transplantation Hypertension one year after transplantation HyperglycemiaDiabetes de novo one year after transplantation Renal function before Tx and 1 year after Tx
Detailed Description:
A Study group
FK506-MMF
Immunosupression protocol
Metylprednisolon 10 mgkg intraoperatively iv
FK506 Day 0 or 1 oraly 015 mgkgD in two doses
MMF max dosage 30 mgkgD po day 0 through day 90 according to patient condition and therapeutic MMF blood concentration
Tailoring
Immunosupression protocol will be tailored according to the cause of liver failure patients with autoimmune liver disease autoimmune hepatitis PBC PSC overlap syndrome etc would be maintained on MMF All other recipients including cryptogenic liver cirrhosis will be gradually over 1 month withdrawn from MMF administration 90 days after transplantation if there is
1 good kidney function S-creatinin 150 umoll enabling to achieve and maintain Tacrolimus trough levels above 6 ngml and
2 if there was no more than one episode of acute rejection of the graft which resolved completely
Targeted Tacrolimus trough levels
Month 1 - 3 through levels 10-15 ngml Month 4-6 10-12 ngml Month 7-12 10 - 6 ngml
Rejection treatment
1 Tacrolimus dose adjustment to upper limit of target level if last Tacrolimus trough level is below the intended limit
2 Steroid boluses would be administered Metylprednisolon 10 mgkg daily 3 consecutive days No steroid taper Control biopsy after normalisation of LFTs
3 After two attacks of acute rejection before MMF disontinuation Prednison dose would be introduced on at least 03 mgD for 3 months
4 After second attack of AR after MMF discontinuation Prednison dose would be introduced on at least 03 mgD for 6 months
5 Steroid resistant rejection biopsy proven rejection persisting after three courses of steroid pulses Steroid resistant rejection would be treated according to local praxis
Concomitant drugs
Antiviral and antibacterial prophylaxis according to current centre praxis Prophylaxis of cholestasis and prophylaxistreatment of the bone disease where applicable
B Control group
Tacrolimus steroids
Immunosupression protocol
Metylprednisolon 10 mgkg bm intraoperatively Children 25kg bm Metylprednisolon taper from 100 mgD on day 0 to MP 10 mg on day 7 Children 25kg bm Metylprednisolon taper from 200 mgD on day 0 to MP 20 mg on day 7 Week 2-4 Prednison - 05-03 mgkgD Week 4-12 Prednison -03-02 mgkgD Month 4-6 Prednison 02 - 01 mgkgD Month 7 - Steroid withdrawal
FK506 Day 0 or 1 orally 015 mgkgD in two doses
Intended Tacrolimus trough levels
Month 1 -3 through levels 10-15 ngml Month 4-6 10-12 ngml Month 7-12 6-10 ngml
Rejection treatment
1 Tacrolimus dose adjustment to upper limit of target level if last Tacrolimus trough level is below the intended limit
2 Steroid boluses would be administered Metylprednisolon 10 mgkg bm daily 3 consecutive days No steroid taper return to previous steroid dose Control biopsy after normalisation of LFTs
3 After two attacks of acute rejection Prednison dose would be maintained on at least 03 mgD for 3 months
4 Steroid resistant rejection biopsy proven rejection persisting after three courses of steroid pulses Steroid resistant rejection would be treated according to local praxis
Biopsy Liver biopsy should be taken in any suspicion of graft rejection or disease recurrence Protocol biopsy would be taken according to local practice liver biopsy in one-year after transplantation is mandatory
Primary end points
Number of rejections number of steroid-resistant rejections
Secondary end points
Patients and graft survival Dyslipidemia one year after transplantation Hypertension one year after transplantation HyperglycemiaDiabetes de novo one year after transplantation Renal function before Tx and 1 year after Tx
Inclusion criteria
Subjects who meet all of the following criteria are eligible for this study
1 Male or female patients not older than 18 years old
2 Primary liver transplantation
3 Patient is capable of understanding the purpose and risks of the study and has been informed both orally and in writing and has given informed consent
Exclusion criteria
Subjects who meet one or more of the following criteria are not eligible for this study
1 Female patients who are pregnant or are breast feeding
2 Patients 18 years old
3 Combined liver-kidney transplantation
4 Recipient of second liver graft
5 Patients are allergic hyper-sensitive or intolerant to HCO-60 or structurally related compounds macrolide antibiotics or tacrolimus
6 Patients with known HIV-anamnesis
7 Patient requires ongoing dosing with a systemic immunosuppressive drug at study entry for another indication than the prophylaxis of liver graft rejection
8 Patient has significant uncontrolled concomitant infections andor severe diarrhea vomiting or active peptic ulcer
9 Patient is participating or has participated in another clinical study andor is taking or has been taking an investigational drug in the past 28 days
10 Other reasons which depend on the assessment of the physician no MMF will be given to patients with severe persistent hypersplenism WBC 3500ml platelets 50000ml
Informed Consent
Patient who will give written consent for participation in the study and will fulfil all the inclusion and exclusion criteria will be included in the study After inclusion into the study the patient may withdraw at any time for any reason
Follow-up time of one patient observation -12 months
Number of centers 1 Number of patients 40 Indication - Primary Liver transplantation Duration of study 36 months Enrollment period 18 months
FK506-MMF
Immunosupression protocol
Metylprednisolon 10 mgkg intraoperatively iv
FK506 Day 0 or 1 oraly 015 mgkgD in two doses
MMF max dosage 30 mgkgD po day 0 through day 90 according to patient condition and therapeutic MMF blood concentration
Tailoring
Immunosupression protocol will be tailored according to the cause of liver failure patients with autoimmune liver disease autoimmune hepatitis PBC PSC overlap syndrome etc would be maintained on MMF All other recipients including cryptogenic liver cirrhosis will be gradually over 1 month withdrawn from MMF administration 90 days after transplantation if there is
1 good kidney function S-creatinin 150 umoll enabling to achieve and maintain Tacrolimus trough levels above 6 ngml and
2 if there was no more than one episode of acute rejection of the graft which resolved completely
Targeted Tacrolimus trough levels
Month 1 - 3 through levels 10-15 ngml Month 4-6 10-12 ngml Month 7-12 10 - 6 ngml
Rejection treatment
1 Tacrolimus dose adjustment to upper limit of target level if last Tacrolimus trough level is below the intended limit
2 Steroid boluses would be administered Metylprednisolon 10 mgkg daily 3 consecutive days No steroid taper Control biopsy after normalisation of LFTs
3 After two attacks of acute rejection before MMF disontinuation Prednison dose would be introduced on at least 03 mgD for 3 months
4 After second attack of AR after MMF discontinuation Prednison dose would be introduced on at least 03 mgD for 6 months
5 Steroid resistant rejection biopsy proven rejection persisting after three courses of steroid pulses Steroid resistant rejection would be treated according to local praxis
Concomitant drugs
Antiviral and antibacterial prophylaxis according to current centre praxis Prophylaxis of cholestasis and prophylaxistreatment of the bone disease where applicable
B Control group
Tacrolimus steroids
Immunosupression protocol
Metylprednisolon 10 mgkg bm intraoperatively Children 25kg bm Metylprednisolon taper from 100 mgD on day 0 to MP 10 mg on day 7 Children 25kg bm Metylprednisolon taper from 200 mgD on day 0 to MP 20 mg on day 7 Week 2-4 Prednison - 05-03 mgkgD Week 4-12 Prednison -03-02 mgkgD Month 4-6 Prednison 02 - 01 mgkgD Month 7 - Steroid withdrawal
FK506 Day 0 or 1 orally 015 mgkgD in two doses
Intended Tacrolimus trough levels
Month 1 -3 through levels 10-15 ngml Month 4-6 10-12 ngml Month 7-12 6-10 ngml
Rejection treatment
1 Tacrolimus dose adjustment to upper limit of target level if last Tacrolimus trough level is below the intended limit
2 Steroid boluses would be administered Metylprednisolon 10 mgkg bm daily 3 consecutive days No steroid taper return to previous steroid dose Control biopsy after normalisation of LFTs
3 After two attacks of acute rejection Prednison dose would be maintained on at least 03 mgD for 3 months
4 Steroid resistant rejection biopsy proven rejection persisting after three courses of steroid pulses Steroid resistant rejection would be treated according to local praxis
Biopsy Liver biopsy should be taken in any suspicion of graft rejection or disease recurrence Protocol biopsy would be taken according to local practice liver biopsy in one-year after transplantation is mandatory
Primary end points
Number of rejections number of steroid-resistant rejections
Secondary end points
Patients and graft survival Dyslipidemia one year after transplantation Hypertension one year after transplantation HyperglycemiaDiabetes de novo one year after transplantation Renal function before Tx and 1 year after Tx
Inclusion criteria
Subjects who meet all of the following criteria are eligible for this study
1 Male or female patients not older than 18 years old
2 Primary liver transplantation
3 Patient is capable of understanding the purpose and risks of the study and has been informed both orally and in writing and has given informed consent
Exclusion criteria
Subjects who meet one or more of the following criteria are not eligible for this study
1 Female patients who are pregnant or are breast feeding
2 Patients 18 years old
3 Combined liver-kidney transplantation
4 Recipient of second liver graft
5 Patients are allergic hyper-sensitive or intolerant to HCO-60 or structurally related compounds macrolide antibiotics or tacrolimus
6 Patients with known HIV-anamnesis
7 Patient requires ongoing dosing with a systemic immunosuppressive drug at study entry for another indication than the prophylaxis of liver graft rejection
8 Patient has significant uncontrolled concomitant infections andor severe diarrhea vomiting or active peptic ulcer
9 Patient is participating or has participated in another clinical study andor is taking or has been taking an investigational drug in the past 28 days
10 Other reasons which depend on the assessment of the physician no MMF will be given to patients with severe persistent hypersplenism WBC 3500ml platelets 50000ml
Informed Consent
Patient who will give written consent for participation in the study and will fulfil all the inclusion and exclusion criteria will be included in the study After inclusion into the study the patient may withdraw at any time for any reason
Follow-up time of one patient observation -12 months
Number of centers 1 Number of patients 40 Indication - Primary Liver transplantation Duration of study 36 months Enrollment period 18 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None