Comparison of Immunosuppression Protocols After LTx in Children

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ClinicalTrials.gov Identifier: NCT00195988

Recruitment Status : Completed

First Posted : September 20, 2005

Last Update Posted : November 17, 2005

Sponsor:

Information provided by:

Children's Memorial Health Institute, Poland

Study Description

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 mg/kg intraoperatively i.v. FK506 Day 0 or 1 orally (0,15 mg/kg/D in two doses).MMF max. dosage 30 mg/kg/D p.o. day 0 through day 90.

B. Control group - Tacrolimus, steroids. Immunosupression protocol: Methylprednisolone 10 mg/kg bm intraoperatively Children < 25kg bm: Methylprednisolone taper from 100 mg/D on day 0 to MP 10 mg on day 7 Children > 25kg bm: Methylprednisolone taper from 200 mg/D on day 0 to MP 20 mg on day 7 Week 2-4 Prednisone - 0,5-0,3 mg/kg/D; Week 4-12 Prednisone -0,3-0,2 mg/kg/D; Month 4-6 Prednisone 0,2 - 0,1 mg/kg/D Month 7 - Steroid withdrawal FK506 Day 0 or 1 orally (0,15 mg/kg/D 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 Hyperglycemia/Diabetes de novo one year after transplantation Renal function before Tx and 1 year after Tx

Condition or disease	Intervention/treatment	Phase
Liver Transplantation	Drug: tacrolimus, steroids, mycophenolate mofetil	Phase 4

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Detailed Description:

A: Study group

FK506-MMF.

Immunosupression protocol:

Metylprednisolon 10 mg/kg intraoperatively i.v.

FK506 Day 0 or 1 oraly (0,15 mg/kg/D in two doses).

MMF max. dosage 30 mg/kg/D p.o. 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 All other recipients including cryptogenic liver cirrhosis will be gradually (over 1 month) withdrawn from MMF administration 90 days after transplantation if there is:

good kidney function (S-creatinin < 150 umol/l) enabling to achieve and maintain Tacrolimus trough levels above 6 ng/ml and
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 ng/ml Month 4-6 10-12 ng/ml Month 7-12 10 - 6 ng/ml

Rejection treatment:

Tacrolimus dose adjustment to upper limit of target level if last Tacrolimus trough level is below the intended limit.
Steroid boluses would be administered Metylprednisolon 10 mg/kg daily 3 consecutive days. No steroid taper. Control biopsy after normalisation of LFTs.
After two attacks of acute rejection before MMF disontinuation Prednison dose would be introduced on at least 0,3 mg/D for 3 months.
After second attack of AR after MMF discontinuation Prednison dose would be introduced on at least 0,3 mg/D for 6 months.
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 prophylaxis/treatment of the bone disease where applicable.

B. Control group

Tacrolimus, steroids.

Immunosupression protocol:

Metylprednisolon 10 mg/kg bm intraoperatively Children < 25kg bm: Metylprednisolon taper from 100 mg/D on day 0 to MP 10 mg on day 7 Children > 25kg bm: Metylprednisolon taper from 200 mg/D on day 0 to MP 20 mg on day 7 Week 2-4 Prednison - 0,5-0,3 mg/kg/D Week 4-12 Prednison -0,3-0,2 mg/kg/D Month 4-6 Prednison 0,2 - 0,1 mg/kg/D Month 7 - Steroid withdrawal

FK506 Day 0 or 1 orally (0,15 mg/kg/D in two doses).

Intended Tacrolimus trough levels:

Month 1 -3 through levels 10-15 ng/ml Month 4-6 10-12 ng/ml Month 7-12 6-10 ng/ml

Rejection treatment:

Tacrolimus dose adjustment to upper limit of target level if last Tacrolimus trough level is below the intended limit.
Steroid boluses would be administered Metylprednisolon 10 mg/kg bm daily 3 consecutive days. No steroid taper, return to previous steroid dose. Control biopsy after normalisation of LFTs.
After two attacks of acute rejection Prednison dose would be maintained on at least 0,3 mg/D for 3 months.
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:

Inclusion criteria:

Subjects who meet all of the following criteria are eligible for this study:

Male or female patients, not older than 18 years old.
Primary liver transplantation
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:

Female patients who are pregnant or are breast feeding
Patients > 18 years old
Combined liver-kidney transplantation
Recipient of second liver graft
Patients are allergic, hyper-sensitive or intolerant to HCO-60 or structurally related compounds, macrolide antibiotics or tacrolimus.
Patients with known HIV-anamnesis
Patient requires ongoing dosing with a systemic immunosuppressive drug at study entry for another indication than the prophylaxis of liver graft rejection
Patient has significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, or active peptic ulcer.
Patient is participating or has participated in another clinical study and/or is taking or has been taking an investigational drug in the past 28 days.
Other reasons which depend on the assessment of the physician (no MMF will be given to patients with severe persistent hypersplenism (WBC < 3.500/ml, platelets < 50.000/ml)

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 Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	40 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Study Start Date :	September 2002
Study Completion Date :	July 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Transplantation

Drug Information available for: Mycophenolic acid Mycophenolate sodium Tacrolimus Mycophenolate mofetil hydrochloride Mycophenolate mofetil

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

Number of rejections, number of steroid-resistant rejections.

Secondary Outcome Measures :

Patients and graft survival
Dyslipidemia one year after transplantation
Hypertension one year after transplantation
Hyperglycemia/Diabetes de novo one year after transplantation
Renal function before Tx and 1 year after Tx

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	up to 18 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 and/or severe diarrhoea, vomiting, or active peptic ulcer.
9. Patient is participating or has participated in another clinical study and/or 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 < 3.500/ml, platelets < 50.000/ml)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00195988

Locations

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Poland
Department of Pediatric Surgery and Organ Transplantation, CMHI
Warsaw, Poland, 04-743

Sponsors and Collaborators

Children's Memorial Health Institute, Poland

Investigators

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Principal Investigator:	Piotr Kalicinski, Prof., MD, PhD	Children's Memorial Health Institute

More Information

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ClinicalTrials.gov Identifier:	NCT00195988
Other Study ID Numbers:	IDS-CZD-piokal
First Posted:	September 20, 2005 Key Record Dates
Last Update Posted:	November 17, 2005
Last Verified:	June 2005

Keywords provided by Children's Memorial Health Institute, Poland:


immunosuppression, steroid avoidance, liver transplantation, children

Additional relevant MeSH terms:

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Mycophenolic Acid Tacrolimus Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Calcineurin Inhibitors Enzyme Inhibitors	Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic Antineoplastic Agents Antibiotics, Antitubercular Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents

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