Pilot Study on the Use of Sirolimus to Treat Chronic Allograft Nephropathy in Children After Kidney Transplant

Study Description

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Brief Summary:

The purpose of this study is to determine whether treatment with sirolimus, in combination with low-dose tacrolimus and prednisone, is effective for the treatment of chronic allograft nephropathy (progressive scarring) in children who have previously received a kidney transplant. This treatment is compared to the standard therapy which uses low-dose tacrolimus, mycophenolate mofetil and prednisons.

This study is a pilot study that will determine whether treatment with sirolimus reduces or improves the rate of scarring seen on kidney biopsy of the transplanted kidney over time, compared to children who continue to be treated with mycophenolate mofetil.

Condition or disease	Intervention/treatment	Phase
Kidney Transplantation	Drug: sirolimus	Phase 4

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Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	40 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase 4 Randomized, Controlled Study Comparing Sirolimus and Mycophenolate Mofetil to Prevent or Reverse Progression in Pediatric Renal Transplants With Chronic Allograft Nephropathy
Study Start Date :	March 2004
Actual Study Completion Date :	October 2008

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

1. histological quantification of interstitial fibrosis at 2 years

Secondary Outcome Measures :

1. Renal function at 1 and 2 years.
2. Proteinuria at 2 years.
3. Freedom from acute rejection and graft loss over the 2 year study period.
4. Cumulative incidence and prevalence of adverse events and serious adverse events over the 2-year study period.

Eligibility Criteria

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Ages Eligible for Study:	6 Years to 18 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• All male or female patients aged less than 17 years.
• The patient has undergone a kidney transplant, from a cadaveric or living donor with compatible ABO blood type.
• The patient is more than 12 months post-transplantation.
• The allograft demonstrates histological changes consistent with CAN according to the Banff 97 classification schema (minimum of ct1 and ci1 score for tubular atrophy and interstitial fibrosis respectively).

Exclusion Criteria:

• The patient, or in case the patient is minor, the patient's parent(s) or their legal representative, has been fully informed and will not give informed consent to participate in the study.
• The allograft demonstrates histological changes at the time of enrollment consistent with acute allograft rejection Grade Ia or worse, according to the Banff 97 classification schema (minimum of t2 and i2 score for tubulitis and interstitial inflammation respectively).
• The patient is known to be allergic or intolerant to MMF, sirolimus or any of their known metabolites.
• The patient for who routine protocol kidney biopsy is contraindicated.
• Patients whose maintenance immunosuppression does not include both tacrolimus and prednisone at the time on study enrollment.
• Patients previously treated with sirolimus.
• The patient requires ongoing dosing with a systemic immunosuppressive drug at study entry for any reason other than kidney transplantation.
• The patient and/or donor is known to be HIV or HCV positive.
• The patient has significant liver disease, defined as having during the past 28 days continuously elevated ASAT (SGOT) and/or ALAT (SGPT) levels greater than 3 times the upper value of the normal range of the investigational site.
• The patient has persistent leukopenia (WBC <3.0 x109/L).
• The patient has persistent thrombocytopenia (<100 x109/L).
• The patient has pre-existing significant hyperlipidemia (total cholesterol >7.8 mmol/L), not responding to medical therapy.
• The patient has pre-existing elevated triglycerides, not responding to medical therapy.
• The patient with malignancy or history of malignancy except for successfully treated Wilm's tumor (2 years) or non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
• The patient has significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting or active peptic ulcer.
• The patient has previously received or is receiving an organ transplant other than kidney.
• The patient is taking or has been taking an investigational drug in the past 28 days or is currently participating in another clinical intervention trial.
• Patients with the relapsing, non-diarrheal form of haemolytic-uraemic syndrome.
• The patient is unlikely to comply with the protocol.
• The patient has any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may invalidate communication with the investigator
• Sexually active female patients who are pregnant or lactating or who do not consent to effective birth control.
• The patient is less than 6 years of age.
• The patient has significant and persistent EBV activity as measured by PCR amplification from blood samples.
• The patient has a prior history of post-transplant lymphoproliferative disease.

Contacts and Locations

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Locations

Canada, Manitoba
Children's Hospital
Winnipeg, Manitoba, Canada, R3A 1S1

Sponsors and Collaborators

University of Manitoba

Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

Principal Investigator:	Tom D. Blydt-Hansen, MD	University of Manitoba, Manitoba Institute of Child Health

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Manitoba Institute of Child Health 

Children's Hospital in Winnipeg 

University of Manitoba 

ClinicalTrials.gov Identifier:	NCT00188955 History of Changes
Other Study ID Numbers:	WINNIPEG-CAN-1
First Posted:	September 16, 2005
Last Update Posted:	February 22, 2010
Last Verified:	February 2010

Keywords provided by University of Manitoba:

pediatric; chronic allograft nephropathy; chronic rejection; interstitial fibrosis

Additional relevant MeSH terms:

Kidney Diseases; Urologic Diseases; Sirolimus; Everolimus; Anti-Bacterial Agents; Anti-Infective Agents	Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs