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Tracking Information | |||||
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First Received Date † | February 23, 2006 | ||||
Last Updated Date | May 28, 2008 | ||||
Start Date † | February 2006 | ||||
Current Primary Outcome Measures † |
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Original Primary Outcome Measures † |
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Change History | Complete list of historical versions of study NCT00296244 on ClinicalTrials.gov Archive Site | ||||
Current Secondary Outcome Measures † |
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Original Secondary Outcome Measures † |
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Descriptive Information | |||||
Brief Title † | Steroid Free Immunosuppression in Liver Transplantation | ||||
Official Title † | Steroid Free Immunosuppression in Liver Transplantation | ||||
Brief Summary | The purpose of this study is to determine whether steroid-related complications can be avoided by using an anti-rejection drug combination without steroids after liver transplantation. |
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Detailed Description | Corticosteroids have remained a standard part of post-transplant immunosuppression, both for prevention and treatment of rejection. However, steroids have been shown to cause long-term adverse effects, such as: susceptibility to infection, obesity, hypertension, hyperlipidemia, diabetes, osteopenia, cataracts and growth retardation in children. They have also been implicated in accelerating Hepatitis C virus re-infection post- liver transplantation. Several studies have shown that early steroid reduction or withdrawal could be done safely to alleviate many corticosteroid related adverse effects after liver transplantation. This is a prospective controlled randomized trial on adult patients who will undergo primary orthotopic liver transplantation at Thomas Jefferson University Hospital. Forty consecutive liver transplant recipients shall be randomized into two groups.
Basiliximab will be given at 20 mg IV bolus intra-operatively and on the 4th day after transplantation. Tacrolimus shall be administered at a dose of 0.15mg/ kg/ day by mouth or through a naso-gastric tube (NGT), starting not earlier than 24 after the transplant but within 48 hrs after reperfusion. The dose shall be adjusted to achieve a trough level of 10-15 ng/ml during the first 30 days after transplantation and lowered to 5-10 ng/ml, thereafter. Patients randomized to Group 2 shall be administered methylprednisolone (Solumedrol) 1000 mg IV during the anhepatic phase. Methylprednisolone will be continued according to the following taper schedule: 50 mg IV every 6 hrs on day 1; 40 mg IV every 6hrs on day 2; 30 mg IV every 6 hrs on day 3; 20 mg IV every 6 hrs on day 4; 20 mg IV every 12 hrs on day 5; and Prednisone 20 mg by mouth or NGT on day 6. Prednisone shall be tapered slowly starting at 1 month post-OLT and weaned off completely by 6 months post-OLT. Myfortic may be added to the regimen, if clinically indicated, i.e., in patients with renal impairment or neuro-toxicity to minimize the dose and effects of tacrolimus. It will be started at 720 mg P.O. 2x/ day immediately post-transplant and shall be given for a period of 3 months. Primary end points of this study at 6 months post-transplant include: graft and patient survival rates, and incidence of rejection and therapy employed to treat rejection. Secondary end points include: adverse effects of steroids, particularly, diabetes, obesity, hyperlipidemia, and hypertension; incidence and severity of Hepatitis C recurrence, and incidence of infectious complications. Blood samples of anti-HCV positive patients shall be collected on day of surgery, 2 weeks, 1 month, 3 months, and 6 months post-OLT as per TJUH Liver Transplant Protocol. Sera shall be stored at -80C and will be used for quantitative HCV RNA levels by quantitative polymerase chain reaction. Protocol liver biopsy shall be performed at the time of surgery, between 7-21 days post-OLT and at approximately 3 months after transplantation or as clinically indicated by elevated liver function test results. Acute rejection shall be treated initially by increasing the tacrolimus dose to achieve a level 15-20 ng/ml for 48 hrs. If liver function test results will not show improvement by the 3rd day after increasing tacrolimus dose, a biopsy should be performed. Only biopsy proven rejection shall be treated according to the following protocol. Mild to moderate rejection shall be treated in the study group with methylprednisolone 1 gm IV with tapering doses of steroid as described above. Steroids shall be discontinued after the completion of the taper. In the control group, methylprednisolone 1 gm IV shall be followed by tapering doses and by prednisone 20 mg once daily, which shall be progressively reduced accordingly. The protocol shall also include a repeat biopsy if there is no improvement in the liver numbers at the end of steroid taper. Severe rejection or steroid resistant rejection shall be treated with OKT3 at 5mg IV/ day for 5-10 days after pre-medication. Recipients with HCV recurrence shall be treated according to TJUH Liver Transplant protocol as follows. Abnormal liver function tests should be evaluated by hepatic imaging to exclude anatomic abnormality. If none, liver biopsy will be done. If liver biopsy shows > grade 4 (inflammation more than mild) or > stage 1 (fibrosis), consider antiviral treatment consisting of Peg-Interferon alpha-2a 180mcg subcutaneously weekly for two weeks. If patient tolerates peg-interferon from hematologic and neuro-psychiatric standpoint, continue peg-interferon, and add ribavirin. Refer to protocol for dosing. Total duration of therapy is 48 weeks. Follow up period for primary analysis will be six (6) months. |
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Study Phase | Phase IV | ||||
Study Type † | Interventional | ||||
Study Design † | Treatment, Randomized, Open Label, Active Control, Factorial Assignment, Safety/Efficacy Study | ||||
Condition † |
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Intervention † |
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Study Arms / Comparison Groups |
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Publications * | |||||
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline. |
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Recruitment Information | |||||
Recruitment Status † | Active, not recruiting | ||||
Enrollment † | 40 | ||||
Estimated Completion Date | June 2008 | ||||
Estimated Primary Completion Date | May 2008 (final data collection date for primary outcome measure) | ||||
Eligibility Criteria † | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both | ||||
Ages | 18 Years to 72 Years | ||||
Accepts Healthy Volunteers | No | ||||
Contacts †† | |||||
Location Countries † | United States | ||||
Expanded Access Status | |||||
Administrative Information | |||||
NCT ID † | NCT00296244 | ||||
Responsible Party | Carlo Ramirez, MD, Thomas Jefferson University | ||||
Secondary IDs †† | |||||
Study Sponsor † | Thomas Jefferson University | ||||
Collaborators †† | Novartis | ||||
Investigators † |
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Information Provided By | Thomas Jefferson University | ||||
Verification Date | May 2008 | ||||
† Required WHO trial registration data element. †† WHO trial registration data element that is required only if it exists. |