Prednisone Withdrawal Versus Prednisone Maintenance After Kidney Transplant

NCT ID: NCT00596947

Last Updated: 2017-05-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2009-03-31

Brief Summary

The purpose of the study was to determine if rapid discontinuation of corticosteroids (also known as prednisone withdrawal) and maintenance immunosuppression with Prograf (tacrolimus) and CellCept (mycophenolate mofetil) while using Thymoglobulin (Rabbit antithymocyte globulin) will give similar safety and efficacy results compared to continuation of corticosteroids (also known as prednisone maintenance) and standard maintenance immunosuppression with Prograf (tacrolimus), CellCept (mycophenolate mofetil) while using Thymoglobulin (Rabbit antithymocyte globulin).

Detailed Description

Corticosteroids (one specific type is prednisone) have been used in clinical transplantation for more than 30 years. There are many side effects of corticosteroids including significant bone disease, diabetes (elevated blood sugar levels), fluid retention and hypertension (high blood pressure), psychosis, peptic ulcer disease, hyperlipidemia (elevated lipid levels such as cholesterol and triglycerides), obesity (overweight), acne, and susceptibility to infections. It is hoped that the new generation of potent immunosuppressive medications (such as Prograf and CellCept) will permit avoidance or withdrawal of corticosteroids for the majority of patients to avoid both short- and long-term complications of corticosteroid use in kidney transplant recipients.

Conditions

Transplants and Implants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prednisone Withdrawal

Participants randomized to the prednisone withdrawal group, received 4 medications to prevent rejection. Thymoglobulin (rabbit antithymocyte globulin) was given intravenously in the operating room at the time of transplant. Subsequent intravenous doses were administered to participants an inpatient or outpatient for a total of 3 to 5 doses. Participants also began taking Prograf (tacrolimus) and CellCept (mycophenolate mofetil)orally within 24 hours of transplant and continued indefinitely. The steroids were initially given in the operating room intravenously at time of transplant as Solu-medrol (methylprednisolone)and were then switched to daily oral prednisone doses. The participant's dose of prednisone was rapidly decreased until it was completely eliminated by day 6 post-transplant.

Group Type: EXPERIMENTAL

prednisone

Intervention Type: DRUG

In this group, participants had prednisone rapidly decreased until completely eliminated by day 6 after transplant. Participants began on 500mg of intravenous methylprednisolone on the day of transplant, followed by the following doses of oral prednisone: 160mg on day 1, 120mg on day 2, 80mg on day 3, 40mg on day 4, 20mg on day 5, none from day 6-on.

rabbit antithymocyte globulin

Intervention Type: DRUG

Participants in both groups received 3 to 5 doses of an intravenous medication to prevent rejection called Thymoglobulin (rabbit antithymocyte globulin) as per our standard of care. This drug was dosed at 1.5 milligrams/killograms per dose and dosing was then based on body weight. The dose was decreased in half or held if the participant had a low white blood cell count or if the participant a low platelet count. The first dose was given intravenously in the operating room and subsequent intravenous doses were administered either while participants were inpatients or outpatients for a total of 3 to 5 doses for a total of up to 6mg/kg. The number of doses was based on transplant kidney function and risk factors for rejection.

Tacrolimus

Intervention Type: DRUG

Participants in both groups received tacrolimus per our standard of care. This medication helped to prevent rejection and was initially dosed at 0.1-0.2 milligrams/killograms/day in two divided doses, given orally, based on participant's body weight. We then looked at the trough levels of this medication(the lowest level before the next dose), and aimed to keep the trough level between 5-10 nanograms/milliliter throughout the study.

Mycophenolate mofetil

Intervention Type: DRUG

Participants in both groups received mycophenolate mofetil by mouth twice daily indefinitely. Dosing for patients in the Prednisone withdrawal group was 1000mg orally twice daily. The dose was decreased or held at the discretion of the physician, for side effects such as low white blood cell count, or low platelet count, or if the participant experienced stomach side effects such as heartburn, nausea, vomiting or diarrhea.

Prednisone Maintenance

Participants randomized to the prednisone maintenance group, received 4 medications to prevent rejection. Thymoglobulin (rabbit antithymocyte globulin) was initiated intravenously in the operating room at the time of transplant. Subsequent intravenous doses were administered an inpatient or outpatient for a total of 3 to 5 doses. Participants began taking Prograf (tacrolimus) and CellCept (mycophenolate mofetil)orally within 24 hours of transplant and continued on them indefinitely. The steroids were initially given intravenously in the operating room at time of transplant as Solu-medrol (methylprednisolone) and were then switched to daily oral prednisone tablets. Participants remained on all drugs according to their doctor's standard of care, and the prednisone was not be eliminated.

Group Type: ACTIVE_COMPARATOR

rabbit antithymocyte globulin

Intervention Type: DRUG

Participants in both groups received 3 to 5 doses of an intravenous medication to prevent rejection called Thymoglobulin (rabbit antithymocyte globulin) as per our standard of care. This drug was dosed at 1.5 milligrams/killograms per dose and dosing was then based on body weight. The dose was decreased in half or held if the participant had a low white blood cell count or if the participant a low platelet count. The first dose was given intravenously in the operating room and subsequent intravenous doses were administered either while participants were inpatients or outpatients for a total of 3 to 5 doses for a total of up to 6mg/kg. The number of doses was based on transplant kidney function and risk factors for rejection.

Tacrolimus

Intervention Type: DRUG

Participants in both groups received tacrolimus per our standard of care. This medication helped to prevent rejection and was initially dosed at 0.1-0.2 milligrams/killograms/day in two divided doses, given orally, based on participant's body weight. We then looked at the trough levels of this medication(the lowest level before the next dose), and aimed to keep the trough level between 5-10 nanograms/milliliter throughout the study.

Prednisone

Intervention Type: DRUG

Participants in this group continued on prednisone indefinitely. Participants began with 500mg of intravenous methylprednisolone on the day of transplant, followed by the following doses of oral prednisone: 160mg on day 1, 120mg on day 2, 80mg on day 3, 40mg on day 4, 20 mg days 5-9, 15 mg day 10-19, 10 mg day 20-24, 7.5 mg day 25-29, and 5mg from day 30-on indefinitely.

Mycophenolate mofetil

Intervention Type: DRUG

Participants in both groups received mycophenolate mofetil by mouth twice daily indefinitely. Dosing for patients in the Prednisone maintenance group was 500 mg orally twice daily. The dose was decreased or held at the discretion of the physician, for side effects such as low white blood cell count, or low platelet count, or if the participant experienced stomach side effects such as heartburn, nausea, vomiting or diarrhea.

Interventions

prednisone

In this group, participants had prednisone rapidly decreased until completely eliminated by day 6 after transplant. Participants began on 500mg of intravenous methylprednisolone on the day of transplant, followed by the following doses of oral prednisone: 160mg on day 1, 120mg on day 2, 80mg on day 3, 40mg on day 4, 20mg on day 5, none from day 6-on.

Intervention Type: DRUG

rabbit antithymocyte globulin

Participants in both groups received 3 to 5 doses of an intravenous medication to prevent rejection called Thymoglobulin (rabbit antithymocyte globulin) as per our standard of care. This drug was dosed at 1.5 milligrams/killograms per dose and dosing was then based on body weight. The dose was decreased in half or held if the participant had a low white blood cell count or if the participant a low platelet count. The first dose was given intravenously in the operating room and subsequent intravenous doses were administered either while participants were inpatients or outpatients for a total of 3 to 5 doses for a total of up to 6mg/kg. The number of doses was based on transplant kidney function and risk factors for rejection.

Intervention Type: DRUG

Tacrolimus

Participants in both groups received tacrolimus per our standard of care. This medication helped to prevent rejection and was initially dosed at 0.1-0.2 milligrams/killograms/day in two divided doses, given orally, based on participant's body weight. We then looked at the trough levels of this medication(the lowest level before the next dose), and aimed to keep the trough level between 5-10 nanograms/milliliter throughout the study.

Intervention Type: DRUG

Prednisone

Participants in this group continued on prednisone indefinitely. Participants began with 500mg of intravenous methylprednisolone on the day of transplant, followed by the following doses of oral prednisone: 160mg on day 1, 120mg on day 2, 80mg on day 3, 40mg on day 4, 20 mg days 5-9, 15 mg day 10-19, 10 mg day 20-24, 7.5 mg day 25-29, and 5mg from day 30-on indefinitely.

Intervention Type: DRUG

Mycophenolate mofetil

Participants in both groups received mycophenolate mofetil by mouth twice daily indefinitely. Dosing for patients in the Prednisone withdrawal group was 1000mg orally twice daily. The dose was decreased or held at the discretion of the physician, for side effects such as low white blood cell count, or low platelet count, or if the participant experienced stomach side effects such as heartburn, nausea, vomiting or diarrhea.

Intervention Type: DRUG

Mycophenolate mofetil

Participants in both groups received mycophenolate mofetil by mouth twice daily indefinitely. Dosing for patients in the Prednisone maintenance group was 500 mg orally twice daily. The dose was decreased or held at the discretion of the physician, for side effects such as low white blood cell count, or low platelet count, or if the participant experienced stomach side effects such as heartburn, nausea, vomiting or diarrhea.

Intervention Type: DRUG

Other Intervention Names

Deltasone; Steroids; Methylprednisolone; Corticosteroids; RATG; Thymoglobulin; Polyclonal antibody; Prograf; Deltasone; Steroids; Methylprednisolone; Corticosteroids; mmf; CellCept; mmf; CellCept

Eligibility Criteria

Inclusion Criteria

• First time kidney transplant recipients who receives a kidney from a cadaveric, living related or living unrelated donor
• Age greater than 18 years and less than 75 years
• Caucasian recipients
• Patients with current low panel reactive antibody (PRA) levels (<10%)
• Patients with signed and dated informed consent
• Women of childbearing potential must have a negative pregnancy test at baseline and agree to use a medically acceptable method of contraception throughout the treatment period.

Exclusion Criteria

• Other than Caucasian ethnicity
• Patients with HIV+ or
• Patients with HbsAg+ or Hepatitis C positive
• Patients with a history of malignancy in the past 5 years
• Patients with active systemic or localized major infection
• Patients with a history of chronic steroid use for other diseases

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Simin Goral

Director, Polycystic Kidney Disease Clinic

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Simin Goral, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania-Renal Electrolyte and Hypertension Division

Locations

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

803242

Identifier Type: -

Identifier Source: org_study_id